TW201130494A - Compositions and methods for inhibiting expression of IL-18 genes - Google Patents

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a IL-18 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a IL-18 gene using said pharmaceutical composition; and methods for inhibiting the expression of IL-18 in a cell.

Description

201130494 6. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to double-stranded ribonucleic acid (dsRNA) and its use to mediate rNAt disruption to inhibit IL-1 8 gene expression. Furthermore, the use of the dsRNA for the treatment of autoimmune diseases and inflammatory diseases is part of the invention, including but not limited to respiratory diseases/conditions such as wheezing and chronic obstructive pulmonary disease (COPD), acute lungs Injury, arthritis and inflammatory bowel disease. Inhibition of IL-1 8 expression by dsRNA can also be used to treat diseases with inflammatory components such as atherosclerosis. [Prior Art] IL-18 is a pro-inflammatory cytokine, which belongs to the IL-1 superfamily and is mainly produced by giant scorpion cells and dendritic cells, but is also produced by other cell types, such as synovial fibroblasts and keratin. Cells and osteoblasts as well as tracheal epithelial cells. IL-1 8 is produced in the cell by biologically deactivating the precursor il-18 precursor. Mature IL-18 is secreted after cleaving the IL-18 precursor by caspase-1, which was originally identified as an IL-Ιβ converting enzyme. After cleavage of the IL-18 precursor by caspase-1, the activated macrophages produce large amounts of mature IL-18. IL-18 was first identified as an inducer of interferon gamma (ΙΡΝ-γ). It works synergistically with IL-12 to induce IFN-[gamma] from several cell types. IL-18 acts both on both Τ and ΝΚ cell maturation' and has been implicated in Th 17 cell responses. IL-18 induces TNF-α, IL-Ιβ, chemokines (such as IL-8, CXCL5, and CCL20) and other inflammatory mediators associated with the pathogenesis of several autoimmune diseases. In addition, IL-18 is increased in rheumatoid synovial tissue by 152219.doc 201130494 plus angiogenic factor VE (3F is produced. Therefore, the biological effects of iL_18 on various cell types have led to the involvement of this cytokine in the pathology of several inflammatory diseases. Many studies in mice and humans have highlighted the role of IL-18 in respiratory disorders. It has been shown that in mice exposed to cigarette smoke and human lungs induces _18 and its performance The amount of lung in the lungs and serum and sputum macrophages increased. Under the control of "/promoter" in the tracheal „ type of cells specifically expressed IL-1 8 transgenic mice showed pulmonary fibrosis and lung qi The knockout mice lacking the interleukin-18 receptor showed a significant decrease in chemotactic hormones, inflammation, and emphysema produced by the response to cigarette smoke. IL-18 is available. As a cofactor for the development of Th1 and Th2 cells, and several studies have subsequently reported that IL-1 8 may be involved in the development of Th2 type diseases such as asthma. In the ovalbumin-induced murine asthma model, in the lung macrophage Cells and bronchi Treatment with increased expression of IL-1 8 in dermal cells and a decrease in IL-18 performance is associated with decreased tracheal inflammation and bronchial hyperreactivity. It has been used in patients with lung injury induced by bleomycin. An increase in IL-18 expression was observed in the lungs of bleomycin-treated mice. These results indicate that IL-18 is involved in the pathogenesis of pulmonary inflammatory diseases such as pulmonary fibrosis, lung injury, asthma, and COPD. Also plays a role in autoimmune diseases. Jl-18 is expressed in synovial tissue and serum of patients with rheumatoid arthritis. Significant IL-18 is administered to mice with collagen-induced arthritis (CIA) Enhance the development and severity of the disease. The circulating IL-18 content of patients with Crohn's disease is 152219.doc 201130494. Compared with the emergence of enteritis, _18 transgenic mice, lack of il_ 1 8 The mouse has been shown to be resistant to experimental colitis. IL-1 8 has been implicated in other diseases associated with or due to inflammatory components. IL-1 8 in patients with atherosclerotic plaque Overexpression in macrophages present in the block The higher content of IL_18 is associated with symptomatic (unstable) plaques, suggesting a role for IL-18 in plaque destabilization. In the rodent atherosclerosis model, 'iL_18 binding protein inhibits IL_18 The development of atherosclerotic lesions is attenuated. Increased levels of IL-18 are found in a variety of tumors. Information from patients and rodent models clearly indicates that IL_8 is a respiratory disease (eg COPD and asthma) An important mediator of inflammatory responses in acute lung injury and autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. IL-18 can also play a role in the pathology of atherosclerosis. The diseases listed above represent diseases that are clearly unmet for medical needs. In the United States, COPD causes approximately 1 million deaths per year and the prevalence rate increases. Statistical extrapolation predicts that by 2020 COPD will be the third leading cause of death in the world. Current therapies do not treat potential inflammation and tissue damage that are considered to be steroid resistant. Around the world, there are about 46, 〇〇〇, 〇〇〇 patients with asthma. Treatment with inhaled glucocorticoids can temporarily reverse the symptoms of the disease. Severe steroid-resistant asthma and aggravated treatment remain unmet medical needs. Although the treatment of atherosclerosis has progressed medically, it is still one of the leading causes of death and morbidity in the world. Double-stranded RNA molecules (dsRNA) have been shown to block gene expression in a highly conserved regulatory mechanism called RNA interference (RNAi). It is expected that downregulation of IL-18 by IL_18 specific 1522l9.doc 201130494 siRNA will reduce the inflammatory effects of IL-18 and thus improve the disease in which this proinflammatory cytokine plays an important role. The use of RNAi is a viable way to develop therapeutically active substances for the treatment of many proliferative diseases. Alternatively, an IL-18 expression inhibitor, and in particular an IL-18 expression inhibitor of the dsRNA molecule of the invention, can be used to treat autoimmune diseases and inflammatory diseases such as atherosclerosis, rheumatoid arthritis and inflammation. Sexual enteropathy, as well as respiratory diseases/disorders (such as asthma and COPD), acute lung injury, and pulmonary fibrosis. SUMMARY OF THE INVENTION The present invention provides a double-stranded ribonucleic acid molecule (dsRNA), and a composition and method for inhibiting the expression of an IL-8 gene in a cell, tissue or mammal using the dsRNA. The present invention also provides compositions and methods for treating pathological conditions and diseases caused by the expression of the IL-18 gene. Such diseases and diseases are, for example, autoimmune diseases and inflammatory diseases such as atherosclerosis and rheumatoid. Arthritis and inflammatory bowel disease, as well as respiratory diseases/conditions (such as asthma and COPD), acute lung injury, and pulmonary fibrosis. Double-version ribonucleic acid (dsRNA) molecules have been shown to block gene expression in a highly conserved regulatory mechanism called rna interference (RNAi). The present invention provides a double-stranded ribonucleic acid (dsRNA) knife capable of selectively and effectively reducing the expression of IL_!8. The use of IL-1 8 RNAi provides a method of therapeutically and/or prophylactically treating diseases/disorders associated with autoimmune diseases and inflammatory diseases. The specific disease eight conditions include atherosclerosis, rheumatoid arthritis and inflammatory bowel disease, as well as respiratory disease / illness (such as asthma and C〇pD), acute lung injury and pulmonary fibrosis treatment and / or prevention Sexual Therapy, the party 152219.doc 201130494 The method comprises administering to humans or animals a targeted IL_182dsRNA. In a preferred embodiment, the dsRNA molecule is capable of inhibiting the il- 18 gene performance by at least 60%, preferably at least 7%, and optimally at least 8%. The present invention also provides compositions and methods for specifically targeting the lungs with IL-18 dsRNA to treat pathological conditions and diseases caused by the expression of the IL-18 gene, including the above. In one embodiment, the invention provides for the inhibition of the expression of the IL_丨8 gene, in particular the double-stranded ribonucleic acid (dsRNA) of the mammalian or human 1L-18 gene. The dsRNA comprises at least two sequences that are complementary to each other. The dsRNA comprises: a sense strand comprising a first sequence and an antisense strand comprising a second sequence, see the sequences provided in the sequence listing and the specific dsRNA pairs provided in Schedules 1 and 2. In one embodiment, the sense strand comprises a sequence that is at least 9% identical to at least a portion of the mRNA encoding IL-18. The sequence is located in a region complementary to the sense strand and the antisense strand, preferably within the nucleotides 2-7 of the 5, terminal of the antisense strand. In a preferred embodiment, the dsRNA specific target φ is directed to the human IL-18 gene. In another embodiment, the dsRNA targets the mouse (Mus musculus) and the rat (Rattus norvegicus) IL-18 gene. In one embodiment, the antisense strand comprises a nucleotide sequence substantially complementary to at least a portion of the mRNA encoding the IL-18 gene, and the length of the complementary region is optimally less than 30 nucleotides. Furthermore, the length (hybrid length) of the dsRNA molecules of the invention described herein is preferably in the range of about 16 to 30 cores: g: acid, especially in the range of about 18 to 28 nucleotides. The length of the helix of about 19, 20, 21, 22, 23 or 24 nucleotides is particularly suitable for use in the context of the invention 152219.doc 201130494. A 19, 21 or 23 nucleotide duplex segment is preferred. The dsRNA is inhibited by at least 60%, preferably at least 7%, and most preferably 8% in vitro after contact with cells expressing the IL-18 gene. Schedule 1 is a preferred molecule for use as a dsRNA of the present invention. Modified dsRNA molecules are also provided herein and are specifically disclosed in Appendix 2, which provides illustrative examples of modified dsRNA molecules of the invention. As indicated above, Table 2 provides illustrative examples of modified dsRNAs of the invention (where the corresponding sense and antisense strands are provided in this table). Table 12 illustrates the relationship between the unmodified preferred molecule shown in Table 1 and the modified dsRNA in Table 2. Further, illustrative modifications of such components of the dsRNA of the invention are provided herein as examples of modifications. Tables 3 and 4 provide selective biological, clinical, and medicinal related parameters for certain dsRNA molecules of the invention. In the evaluation of therapeutic dsRNA, it is particularly useful as a dsRNA group targeting mouse and rat IL-18, which can be used to estimate the toxicity, therapeutic efficacy and effective dose of individual dsRNA in an animal or cell culture model, and in vivo. half life. Schedule 4 and Schedule 5 are preferred molecules for targeting murine IL-18. Table 5 provides illustrative examples of modified dsRNAs that target murine IL-18 (where the corresponding sense and antisense strands are provided in this table). Table 6 provides the selective biological, clinical, and medicinal related parameters of certain dsRNA molecules of the invention. Table 13 illustrates the relationship between the unmodified preferred molecules shown in Table 4 and the modified dsRNA of Table 5. The optimal dsRNA molecule is provided in the schedule, and particularly and preferably, 152219.doc 201130494 wherein the sense strand is selected from the group consisting of SEQ ID NO: 1, 3, 7, 9, 13, 15, 17, 1 9 a group consisting of the nucleic acid sequences described in 27 and 31, and the antisense strands are selected from the group consisting of the nucleic acid sequences described by SEQ ID NOS: 2, 4, 8, 10, 14, 16, 18, 20, 28 and 32 . Thus, a dsRNA molecule of the invention may comprise, inter alia, selected from the group consisting of SEQ ID NO: 1/2, 3/4, 7/8, 9/10, 13/14, 15/16, 17/18, 19/20, 27/28 And a paired sequence of 3 1/32 groups. In the case of the specific dsRN A molecule provided herein, each pair φ SEQ ID N0 is for the corresponding sense strand and the antisense strand sequence (5, to 3,), which are also shown and included in In the table. In one embodiment, the dsRNA molecules comprise 3, 1 to 2 nucleotides in length, preferably 1 to 2 nucleotides in length, overhangs. Preferably, the overhang comprises uracil or a nucleotide complementary to the mRNA encoding IL-18. In another preferred embodiment, the dsRNA molecules comprise from i to 5 nucleotides in length, preferably from 3 of the length of 2 nucleotides, the overhang of the sense version of the protrusion preferably comprises uracil or a nucleotide which is related to the mRNA encoding IL-18. The dsRNA molecules comprise a sense strand having a length of nucleotides, preferably up to 2 nucleotides in length, a sense strand of the protrusions and having a length of 1 to 5 nucleotides, preferably up to 2 cores. Preferably, the overhang of the sense strand comprises a urinary guanidine or a nucleotide acid which is at least 9% identical to the IL-^ mRNA, and the antisense strand is 4 The protrusion comprises a urinary biting or a nucleotide complementary to the coding, at least 鄕. 152219.doc 201130494 The dsRNA molecule of the invention may comprise a naturally occurring nucleoside The acid may comprise at least one modified nucleotide, such as a 2,_〇-mercapto-modified nucleotide, a 5, a fluorene-methyl modified nucleotide, a nucleoside comprising a 5,-thiophosphate group. An acid, and a terminal nucleotide attached to a cholesteryl derivative or a bis-decyl guanidinoamine group. The 2' modified nucleotide may have another advantage: when the dsRNA molecule of the present invention is used in vivo, for example, Certain immunostimulatory factors or cytokines are inhibited in a medical setting. Alternatively, and without limitation, the modified nucleotide can be selected from the group consisting of 2'-a 2, a fluorine-modified nucleotide, 2 , deoxygenated nucleotides, locked nucleotides, abasic nucleotides, 2,-amino modified nucleotides, 2,-alkyl modified Nucleotides, N-morpholino nucleotides, phosphoramidates, and nucleotides comprising non-natural bases. In a preferred embodiment, the 'dsRNA molecule comprises at least one The following modified nucleotides: 2'-〇-fluorenyl modified nucleotides, 5, 〇-methyl modified nucleotides, containing 5·-sulfur Filled with acid vinegar nucleotides, 2. Fluorine modified deoxythymidine and 5' phosphate group at the 5' end of the antisense strand. Preferred dsRNA molecules comprising modified nucleotides are provided in Table 2. In a preferred embodiment, the dsRNA molecules of the invention comprise modified nucleotides as detailed in the sequences provided in Table 2. In a preferred embodiment, the dsRNA molecules of the invention comprise a selected from the group consisting of *SEQ ID ν〇 Paired sequences of groups of μ/2, 3/4, 7/8, 9/1〇, 13/14, 15/16, 17/18, 19/2〇, 27/28, and 31/32, and Overhangs are included on the antisense strands and/or the sense strands of 1-2 deoxythymidine. In a preferred embodiment, the present invention comprises selected from the group consisting of SEQ ID NO: 1/2, 3/4, 7/8, 9/1Q, 1522l9.doc • JO·201130494 13/14, Paired sequences of groups consisting of 15/16, 17/18, 19/20, 27/28, and 31/32, and including modifications as detailed in Table 2. Preferred dsRNA molecules comprising a modified nucleotide acid are listed in Table 4, wherein the preferred dsRNA molecules are SEQ ID No: 149/150, 163/164, 165/166, 179/180, 183/184, 185/186 187/188, 213/214, 215/216, 217/218, 239/240, 253/254, 255/256, 293/294, 435/436, 461/462, 463/464, 471/472, 475 /476, 479/480 and 487/488 are described. Optimal dsRNA molecules • Described as SEQ ID Nos. 165/166, 239/240 and 255/256. In another embodiment, the dsRNA of the invention comprises modified nucleotides at positions other than those disclosed in Table 2. In a preferred embodiment, two deoxythymidine nucleotides are present at 3' of the two strands of the dsRNA molecule. In one embodiment, the dsRNA molecule of the invention comprises a sense strand and an antisense strand, wherein both strands have a half-life of at least 7 hours. In a preferred embodiment, the dsRNA molecule of the invention comprises a sense strand and an antisense strand, wherein both strands have a half-life φ phase of at least 1.9 hours in human sputum (ARDS). In another embodiment, the dsRNA molecules of the invention are not immunostimulatory, e.g., do not stimulate IFN-[alpha] and TNF-[alpha] in vitro. In another embodiment, the dsRNA molecules of the invention stimulate IFN-a and TNF-a to a very small extent in vitro. The invention also provides a cell comprising at least one dsRNA of the invention. The cell is preferably a mammalian cell, such as a human cell. Furthermore, tissues and/or non-human organisms comprising a dsRNA molecule as defined herein are also encompassed by the invention, wherein the non-human organism is particularly suitable for research purposes or as a research tool, for example also for drug testing. Further, the present invention relates to a method for inhibiting the expression of an IL-18 gene, particularly a mammalian or human IL-18 gene, in a cell, tissue or organism, comprising the steps of: (a) A double-stranded ribonucleic acid (dsRNA) as defined herein is introduced into a cell, tissue or organism; (b) maintaining the time, in which the cell, tissue or organism produced in step (a) is sufficient to achieve mRNA transcript degradation of the IL-18 gene Thereby, the expression of the IL-18 gene in a given cell is inhibited. The invention also relates to pharmaceutical compositions comprising the dsRNA of the invention. These pharmaceutical compositions are especially useful for inhibiting the expression of IL-18 genes in cells, tissues or organisms. Pharmaceutical compositions comprising one or more of the dsRNAs of the invention may also comprise a pharmaceutically acceptable carrier, diluent and/or excipient. In another embodiment, the invention provides methods of treating, preventing, or managing an autoimmune disease and an inflammatory disease associated with IL-18, such as atherosclerosis, rheumatoid arthritis, and inflammatory bowel disease, And respiratory diseases/conditions (such as asthma and COPD), acute lung injury, and pulmonary fibrosis, the method comprising administering to the individual in need of such treatment, prevention, or management a therapeutically or prophylactically effective amount of one or more dsRNAs of the invention. The individual is preferably a mammal, preferably a human patient. In one embodiment, the invention provides a method of treating an individual having a pathological condition mediated by the expression of the Jiang-18 gene. Such conditions include conditions associated with autoimmune diseases and inflammatory diseases such as atherosclerosis, rheumatoid arthritis and inflammatory bowel disease, as well as respiratory diseases/conditions (such as asthma and COPD), acute lung injury and Pulmonary Fibrosis. 152219.doc 201130494 In this example, dSRNA was used as a therapeutic agent for controlling the expression of the Jiang-18 gene. The method comprises administering to a patient (e.g., a human) a pharmaceutical composition of the invention to keep the IL-18 gene expression silent. Due to the high specificity of the dsRNA of the present invention, its specificity is directed to the claw of the IL_18 gene (10). In a preferred embodiment, the dsRNA specifically reduces the IL_18 mRNA content and does not directly express the H cell-de-t gene (Qff_tai<get gene) and/or mRNA content. In a preferred embodiment, the dsRNA reduces the content of il·18 mRNA in the lung by at least 6〇%, preferably at least 7〇%, optimally at least 80/〇 in another embodiment, The dsRNA reduces the il-18 mRNA content in vivo for at least 4 days. In another embodiment, the invention provides for the expression of an IL_丨8 gene in a suppressor cell, in particular comprising a regulatory sequence operably linked to a nucleotide sequence encoding at least one strand of a dsRNA of the invention. A vector for the expression of genes. In another embodiment, the invention provides a cell comprising a vector that inhibits the expression of a . The vector comprises a regulatory sequence operably linked to a nucleotide sequence encoding at least one strand of a dsRNA of the invention. However, in addition to the regulatory sequences, the vector preferably further comprises a sequence encoding at least one "sense strand" of the dsRNA of the invention and at least one "antisense strand" of the dsRNA. It is also contemplated that the claimed cells comprise two or more vectors which, in addition to the regulatory sequences, comprise a sequence encoding at least one strand of a dsRNA of the invention as defined herein. In one embodiment, the method comprises administering a combination comprising dsIllsrA 152219.doc-13-201130494' wherein the dsRNA comprises a nuclear-acid sequence complementary to at least a portion of an RNA transcript of the IL_18 gene of the mammal being treated . As indicated above, vectors and cells comprising at least one nucleic acid/knife encoding a dsRNA molecule as defined herein can also be used as a pharmaceutical composition, and thus can also be used in the methods disclosed herein for treating an individual in need of medical intervention. in. It is also worth noting that such embodiments of pharmaceutical compositions and corresponding methods for treating (human) individuals also relate to methods such as gene therapy. π An IL-18-specific dsRNA molecule as provided herein or a nucleic acid molecule encoding such individual strands of the dsRNA* of the present invention can be inserted into a vector and used as a gene therapy vector for human patients. This can be done, for example, by intravenous injection, topical administration (see U.S. Patent No. 328,470) or by stereotactic injection (9) (10) (10) (5) (10) (see, for example, Chen et al. (1994) Pr〇c. Acad. Sci. USA 91 :3054- 3057) Delivery of gene therapy vectors to individuals. The pharmaceutical preparation of the gene therapy vector may comprise a gene therapy vector in an acceptable diluent, or may comprise a slow release matrix embedded with a gene delivery vehicle. Alternatively, if a complete gene delivery vector (e. g., a retroviral vector) can be prepared from recombinant cells, the pharmaceutical preparation can include one or more cells that produce a gene delivery system. In another aspect of the invention, the transcription unit from the inserted DNA or RNA vector exhibits a 虬18-specific dsRNA molecule that modulates the activity of the IL-18 gene (see, for example, Skillern, Α· et al., International PCT Publication) No. w〇00/22113). Such transgenic genes can be introduced and inherited in the form of linear constructs, cyclic plastids or viral vectors which can be integrated into the host genome. Transgenic genes can also be constructed to be inherited as stained in vitro plastids (Gassmann et al., proc. Natl. Acad 152219.doc • 14 - 201130494

Sci. USA (1995) 92:1292). Individual strands of dsRNA can be co-transfected into the stem cells by promoters on two separate expression vectors. Alternatively, individual strands of the dsRNA can be transcribed from two promoters that are both on the same expression plastid. In a preferred embodiment, the dsRNA is expressed as an inverted repeat joined by a ligated polynucleotide sequence such that the dsRNA has a stem and loop structure. • The recombinant dsRNA expression vector is preferably a DNA plastid or a viral vector. Viral vectors expressing dsRNA can be constructed based on, but not limited to, the following viruses: adeno-associated viruses (for review, see Muzyczka et al, Cwrr. Tbph /mww «c»/(1992) 158:97-129)); Adenovirus (see, for example, Berkner et al. 'BioTechniques (1998) 6: 616; Rosenfeld et al. (1991, Science 252: 431-434); and Rosenfeld et al. (1992), Ce//68: 143-155)); Or alphavirus; and other viruses known in the art. Retroviruses have been used to introduce a variety of genes into many different cell types, including epithelial cells, in vitro and/or in vivo (see, for example, Danos and Mulligan, iVoc. (1998) 85:6460-6464). A recombinant retroviral vector capable of transducing and expressing a gene inserted into a genome of a cell can be produced by transfecting a recombinant retroviral genome into a suitable packaging cell line such as PA3 17 and Psi-CRIP (Comette et al.' 1991 , Human Gene Therapy 2: 5-10; Cone et al., 1984, Proc. Natl. Acad. Sci. USA 81:6349). Recombinant adenoviral vectors can be used to infect a variety of cells and tissues in susceptible hosts (e.g., rats, hamsters, dogs, and chimpanzees) (Hsu et al., 1992, J. Infectious Disease, 152219.doc • 15-201130494 166:769) And also has the advantage of not requiring mitotically active cells for infection. Promoters for driving dsRNAs in the DNA plastid or viral vector of the invention may be eukaryotic RNA polymerase I promoters (eg, ribosomal RNA promoters), RNA polymerase II promoters (eg, CMV early promoters or actin a protein promoter or a U1 snRNA promoter) or preferably an RNA polymerase III promoter (eg, a U6 snRNA or 7SK RNA promoter) or a prokaryotic promoter (eg, a T7 promoter), the restriction is that the expression plasmid is also encoded from The T7 RNA polymerase required for transcription of the T7 promoter. The promoter can also direct the expression of the transgene into the sputum (see, for example, the insulin regulatory sequence of the pancreas (Bucchini et al., 1986, Proc. Natl. Acad. Sci_ USA 83: 25 1 1-25 15)). In addition, the expression of the transgene can be precisely regulated, for example by using inducible regulatory sequences and expression systems, such as regulatory sequences sensitive to certain physiological regulators (eg circulating glucose levels or hormones) (Docherty et al., 1994, FASEB J 8:20-24" These inducible expression systems suitable for controlling the expression of transgenic genes in cells or mammals include ecdys〇ne, estrogen, progesterone, tetracycline, dimerization Chemical inducers and isopropyl-β-Dl-thiogalactopyranoside (EPTG) are regulated. Those skilled in the art will be able to select appropriate regulatory/promoter sequences based on the intended use of the dsRNA transgene. The recombinant vector capable of expressing the dsRNA molecule is preferably delivered as described below and retained in the target cell. Alternatively, a viral vector providing a transient expression of the dsRNA molecule can be used. If necessary, the vector can be repeatedly administered. The expression dsRNA binds to the target RNA and modulates its function or expression. 152219.doc -16 - 201130494 The delivery of the dsRNA expression vector can be administered either wholly or intramuscularly; Self-reintroduction into the patient; or by allowing other means. Physical transfer, such as by stem cells explanted by intravenous patients, followed by any of the desired stem cells, the dsRNA is typically expressed as a DNA plastid with cationic lipids. Transfection of a carrier (eg OHgofectamine) or a complex based on a non-cationic lipid carrier (eg τ^ηΑ·TK〇TM) into the target cell. Targeting a single -18 gene or multiple 1L_18 genes Multiple lipid transfections of different regions, such as 介 八 八 敲 经 经 经 周 周 周 周 周 周 周 周 周 周 周 周 周 周 周 周 周 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重 多重Successful introduction. For example, a reporter (such as a fluorescent label, such as green fluorescent protein (GFP)) can be used to transmit signals for transient transfection. It can be used to provide resistance to specific environmental factors (such as antibiotics and drugs). Labels of transfected cells (such as hygromycin B (hygr〇myCin B) resistance) to ensure stable transfection of ex vivo cells. The following detailed description reveals how to make and use dsRNA and Compositions and methods for inhibiting the expression of the IL-18 gene, and for treating diseases and conditions caused by the expression of the il-1 & gene, as defined by the present specification, examples and The meanings of certain terms and phrases used in the scope of the patent application are attached. If there is a significant difference between the usage of the terms in the other parts of this specification and the definitions provided in this section, then The definitions shall prevail. "G", "C", "A", "U" and "T" or "dT" respectively represent 152219.doc -17- 201130494, which respectively contain bird material, cell (four), gland cut, Urine (tetra) and deoxythymidine are used as nucleotides of bases. Missing, $, "文,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 4 Sequences containing such substitutions are examples of the invention. As detailed below, the NA molecules described herein may also contain "overhangs", which are unpaired prominent nucleotides, which are not directly included in the definition of "righteous shares". The RNA double helix structure towel formed by Xiao "antisense stock". This (iv) out segment often contains deoxythionia picric acid. In most embodiments, at the 3' end, it contains 2 • deoxygenated thoracic. These protrusions are described and illustrated below. The term "IL_18" as used herein refers to interleukin-18', also known as IL18 or IL-18, and the term relates to the corresponding gene, the encoded mRNA, the encoded protein/polypeptide, and functional fragments thereof. The protein encoded by this gene is a pro-inflammatory cytokine. The human IL-18 gene is preferred. In other preferred embodiments, the dsRNA of the invention targets the human (H sapiens) IL·18 gene and the cynom〇igOUS monkey/MacaCa fascicularis IL-18 gene. The dsRNA targeting the IL18 gene of rat (Rattus norvegicus) and mouse (Mus musculus) is also part of the invention. The term "IL-i8 gene/sequence" relates not only to wild-type sequences, but also to mutations and changes that can be included in the gene/sequence. Thus the invention is not limited to the specific dsRNA molecules provided herein. The invention also relates to a dsRNA molecule comprising an antisense strand that is at least 85% complementary to the corresponding nucleolytic acid fragment of an RNA transcript comprising such a mutant/variant IL-18 gene. As used herein, "target sequence" refers to a contiguous portion of the nucleotide sequence of an mRNA molecule formed during the transcription of the IL-18 gene, 152219.doc -18 - 201130494, including mRNA as a major transcript of RNA processing products. . The term "sequence containing a strand" as used herein refers to a nucleotide comprising a nucleotide chain, which is described by the sequence referred to using standard nucleotide nomenclature. However, as described in detail herein, such "stocks containing a sequence" may also include modifications, such as modified nucleotides. As used herein and unless otherwise indicated, the term "complementary" when used in relation to φ to describe the relationship between a first nucleotide sequence and a second nucleotide sequence, refers to a nucleotide comprising a first nucleotide sequence. Or the ability of a polynucleotide to hybridize to an oligonucleotide or polynucleotide comprising a second nucleotide sequence under certain conditions and to form a helicoid structure. A "complementary" sequence as used herein may also include a non-Watson-Crick base pair and/or a base pair formed from a non-natural and modified nucleotide, or The Watson-Crick base pair and/or the base pair formed from the non-natural and modified nucleotides may be formed as long as the above requirements are satisfied in terms of their ability to hybridize. # Sequences referred to as "fully complementary" include: an oligonucleotide or polynucleotide comprising a first nucleotide sequence and a nucleotide or polynucleotide comprising a second nucleotide sequence in a first core The base pairing over the entire length of the nucleotide sequence and the second nucleotide sequence. However, 'if the first sequence is referred to herein as being "substantially complementary" to the second sequence, the two sequences may be fully complementary, or they may form one or more 'but preferably no more than 13 after hybridization. Mismatched base pairs. The terms "complementary", "completely complementary" and "substantially complementary" are used herein to refer to between the sense strand and the antisense strand of the dsRNA or between the dsRNA antisense strand and the dry sequence of the label 152219.doc •19·201130494. Base-matching to use 'as understood in its use case 0 as used herein, the term UOXV1X/1, knives 'd' double "dsRNA" refers to a pair of nucleic acid strands comprising two antiparallel and substantially complementary nucleic acids A ribonucleic acid molecule or a ribonucleic acid molecule complex of a spirochete structure. The two strands forming the duplex structure may be different portions of a larger rNA molecule or may be separate RNA molecules. If the two strands are part of a larger molecule and thus are joined between the 31 ends of one of the strands forming the duplex structure and the 5' end of the other strand, via an uninterrupted nucleotide strand, the connective RNA strand will be It is called "hairpin l〇op" p. If two strands are formed in one of the strands of the double helix structure, the end is separated from the other end of the other strand by a non-uninterrupted nucleotide strand. For covalent connections, the connection structure is called a "linker." The RNA strands can have the same or a different number of nucleotides. In addition to the duplex structure, the dsRNA may also comprise one or more nucleotide overhangs. The nucleotides in the "protrusions" may contain up to 5 nucleotides, wherein "〇" means that no other nucleotide forms a "protrusion", and "5" means a double helix of dsRNA. There are five other nuclear bitter acids on individual stocks. The "protrusions" in these cases are located at the 3rd end of the individual shares. As will be described in more detail below, only one of the two strands containing "overhangs" may be applicable and even advantageous in the context of the present invention. The "protrusion" preferably contains 0 to 2 nucleotides. The best in the 3, there are 2 "dT" (deoxygenated chest) nuclear bitter acid. 2 Γυ" (urine shouting) nuclear acid can also be used as the 3, the end of the two strands of dsRNA. Thus, "nucleotide overhang" means unpaired nucleotide acid or when the 3' end of the dsRNA extends beyond the 5' end of the other 1522l9.doc • 20-201130494 (or vice versa) The dsRNA has a double-helical structure with prominent nucleotides. For example, the S' antisense strand contains 23 cores (four) and the sense strand contains 21 nucleotides to form a 2 nucleotide overhang at the 3' end of the antisense strand. 2 . "The blunt nucleotide overhang is preferably completely complementary to the mRNA of the target gene" or "blunt" means that there is no unpaired nucleotide at the other end of the dsRNA, i.e., a nuclear-free picuric acid overhang. The "blunt end" is a double-stranded dSRNA that is double-stranded throughout its length.

Produce. The term "anti-t-share" includes the secret stock of the domain that is substantially complementary to the standard light sequence. The term "complementary region" as used herein refers to a region on an antisense strand that is substantially complementary to a sequence (e.g., a sequence of (4)). If the complementary region is not completely complementary to the (iv) sequence, then the most tolerated external nucleotide 2-7 of the 5' end of the antisense strand is missed. The term "sense stock" as used in the text refers to a stock of stocks that includes an area that is substantially complementary to an area of the antisense stock. "Substantially complementary" means that at least 85% of the overlapping nucleotides are preferably complementary to the antisense stock. "Introduction into a cell" when referring to dSRNA means promoting uptake or absorption into a cell, as is known to those skilled in the art. Absorption or capture of dsRNA can be carried out by unassisted diffusion or active cellular processes or by adjuvants or devices. The meaning of this term is not limited to in vitro cells; dsRNA can also be "introduced into a cell" where the cell is part of a living organism. In this situation,? Intrusion into cells will include delivery to the organism. For example, for in vivo delivery, dsRNA can be injected into a tissue site or administered systemically. For example, it is envisaged to administer the invention 2 152219.doc 201130494 dsRNA molecule to an individual in need of medical intervention. Such administration can involve injecting a dsRNA, vector or cell of the invention into the diseased side of the subject', e.g., into the lung tissue/cell. Also want to inject near the diseased tissue. Introduction into cells ex vivo includes methods known in the art, such as electroporation and lipofection. The term "inflammatory" as used herein refers to a biological response of body tissue to damage, puncture, or disease that may be caused by noxious stimuli (e.g., pathogens), damaged cells, or irritants. Inflammation is usually characterized by pain and swelling. Inflammation encompasses an acute reaction in which the inflammatory process is active (such as neutrophils and white blood cells), and a chronic response characterized by slow progression, changes in cell types present at the site of inflammation, and formation of connective tissue. "Session", "inhibition" and "knockout" in the context of the case of the IL-18 gene are referred to herein as at least partially inhibiting the expression of the il_i8 gene as seen from the IL-18 gene. The amount of transcription of the sputum gene isolated by the first cell or cell population that inhibits the expression of the IL_18 gene is compared to the first cell or cell population (control cell) that is substantially identical to the first cell or cell population but has not been so treated. The decrease in mRNA transcription is shown. The degree of inhibition is usually expressed as follows: In the mRNA of the mRNA in the cell, the intercellular cells are 100/o. Alternatively, the degree of inhibition can be expressed by a decrease in the functionally related parameter of IL-18 gene transcription, The parameter is, for example, the amount of protein encoded by the il. 18 factor secreted by the cell or the number of cells displaying a certain phenotype. 1522l9.doc -22- 201130494 As described in the accompanying examples and in the schedule provided herein, the dsRNA molecules of the invention are capable of at least about 60% of the performance of human il_18 in an in vitro assay (ie, in vitro), Preferably at least 70%, optimally at least 8% inhibition. The term "in vitro" as used herein includes, but is not limited to, cell culture assays. In another embodiment, the dsRNA molecules of the invention are capable of subjecting mouse or rat IL-18 to at least 60°/. Preferably, it is at least 70%, preferably at least 80% inhibited. Such inhibition rates and related effects can be readily determined by those skilled in the art, especially in accordance with the assays provided herein. The term "off-target" as used herein refers to all non-target mRNAs of a transcriptome predicted by the electronic hybridization (in siiico) method to hybridize to the dsRNA based on sequence complementarity. The dsRNA of the present invention preferably specifically inhibits the expression of il- 18, i.e., does not inhibit any off-target performance. As used herein, "half-coating period" is a measure of compound or molecular stability and can be assessed by methods known to those skilled in the art, especially in accordance with the assays provided herein. The term "not immunostimulatory" as used herein means that the dsRNA molecule of the invention does not have any induction of an immune response. Methods for determining an immune response are well known to those skilled in the art, for example by assessing cytokine release, as described in the Examples section. The "treatment" and similar expressions in the context of the present invention mean alleviating or ameliorating conditions associated with IL-18 performance, such as inflammatory and proliferative disorders, such as cancer. A "pharmaceutical composition" as used herein includes a pharmacologically effective amount of dsRNA and a pharmaceutically acceptable carrier. However, such "pharmaceutical combination 1522l9.doc -23-201130494" may also comprise individual strands of such dsRNA molecules or vectors described herein. The vector contains regulatory sequences operably linked to the coding contained in A nucleotide sequence of at least one of a sense strand or an antisense strand in a dsRNA of the invention. It is also contemplated that cells, tissues or ex vivo organs that exhibit or comprise a dsRNA as defined herein may be used as "pharmaceutical compositions as used herein as "pharmacologically effective amount", "therapeutically effective amount" or simply "effective amount" means The amount of RNA that effectively produces the desired pharmacological, therapeutic, or prophylactic results. 3 "Pharmaceutically acceptable carrier" means a carrier for administration of a therapeutic agent. Such carriers include, but are not limited to, saline, buffered saline, dextrose, water, glycerol, ethanol, and Its combination. This term specifically excludes cell culture groups. For oral administration of a drug, pharmaceutically acceptable carriers include, but are not limited to, pharmaceutically acceptable excipients known to those skilled in the art, such as inert diluents, disintegrating agents, Adhesives, lubricants, sweeteners, flavorings, colorants and preservatives. It is specifically contemplated that a pharmaceutically acceptable carrier will allow for systemic administration of the dsRNA, vector or cell of the invention. Although it is also envisaged that enteral administration but parenteral administration and transdermal or transmucosal (eg, insufflation, buccal, transvaginal, transanal) administration and inhalation of drugs continue to administer the invention to patients in need of medical intervention. A viable way of compounding. When parenteral administration is employed, this can include direct injection of the compound of the invention into or at least the vicinity of the diseased tissue. However, the intravenous, intraarterial, subcutaneous, intramuscular, intraperitoneal, intradermal, (four) and other modes of administration of the compounds of the invention are also within the skill of those skilled in the art (e.g., attending physician). For intramuscular, subcutaneous and intravenous use, the pharmaceutical compositions of the present invention 1522l9.doc • 24· 201130494 will generally be provided in the form of a sterile aqueous solution or suspension which is buffered to the appropriate pH and isotonicity. In a preferred embodiment, the carrier is exclusively comprised of an aqueous buffer. In this context, "exclusively" means that there are no adjuvants or encapsulating substances that may affect or mediate dsRNA uptake in cells expressing the IL-18 gene. The aqueous suspensions of the present invention may include suspending agents such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and tragacanth' and wetting agents such as lecithin. Preservatives suitable for aqueous suspensions include p-hydroxybenzoic acid φ ethyl acetonate and n-propyl p-hydroxybenzoate. Pharmaceutical compositions suitable for use in accordance with the present invention also include encapsulated formulations to protect dsRNA from rapid elimination from the body' such as controlled release formulations' including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods of preparing such formulations will be apparent to those skilled in the art. Liposomal suspensions can also be employed as pharmaceutically acceptable carriers. Such materials can be prepared according to methods known to those skilled in the art, for example, as described in PCT Publication No. WO 91/06309, which is incorporated herein by reference. A "transformed cell" as used herein is a cell into which at least one vector has been introduced, from which at least one strand of a dsRNA molecule or such a dsRNA molecule can be expressed. Such vectors are preferably vectors comprising a regulatory sequence operably linked to a nucleotide sequence encoding at least one of the sense or antisense strands contained in the dsRNA of the invention. It is reasonable to expect that a shorter dsRNA comprising one or both ends minus one of the sequences of Tables 1 and 4 of only a few nucleotides may have 152219.doc •25- 201130494

Similar efficacy D As indicated above, in most embodiments of the invention, the dsRNA molecules provided herein comprise a double helix length of from about 16 to about 3 nucleotides (i.e., no "overhangs"). Particularly suitable dsRNA duplexes are from about 19 to about 25 nucleotides in length. The 19-nucleotide double helix structure is optimal. In the dsRNA molecules of the invention, the antisense strand is at least partially complementary to the sense strand. The dsRNA of the invention may contain one or more mismatches relative to the target sequence. In a preferred embodiment, the dsRNA of the invention contains no more than 13 mismatches. If the antisense strand of the dsRNA contains a mismatch relative to the target sequence, then the mismatch region is preferably not located within the antisense strand 5, nucleotides 2-7 of the end. In another embodiment, the ' mismatch region is preferably not located within the antisense strand 5, the nucleotide of the terminal 2-9. As mentioned above, at least one end/strand of the dsRNA can have from 1 to 5, preferably 1 or 2 nucleotides of single-stranded nucleotide overhang. A dsRNA having at least one nucleotide overhang has extremely excellent inhibitory properties compared to its blunt end counterpart. Furthermore, the inventors have found that the presence of a single nucleotide overhang enhances the interfering activity of the dsRNA without affecting its overall stability. dsRNAs with only one overhang have proven to be particularly stable and effective in vivo as well as in a variety of cells, cell culture media, blood and serum. The single-stranded projection is preferably located at the 3' end of the antisense strand or at the end of the sense strand. The dsRNA may also have a blunt end preferably located at the 5' end of the antisense strand. Preferably, the antisense strand of the dsRNA has a nucleoside protrusion at the 3' end and a blunt end at the 5' end. In another embodiment, one or more nucleotides in the overhang are replaced by a thiosulfate nucleus. I52219.doc • 26- 201130494 The dsRNA of the invention may also be chemically modified to enhance stability. The nucleic acids of the present invention can be synthesized and/or modified by methods that have been used in the art for a long time, such as "Current protocols in nucleic acid chemistry", Beaucage, SL et al. (eds.), J〇hn Wiley & Sons, Inc., New

The method described in York, NY, USA, which is incorporated herein by reference. Chemical modifications can include, but are not limited to, 2, modification, introduction of a non-natural test group, covalent attachment to a ligand, and replacement of a phospho φ vinegar linkage with a phosphorothioate linkage. In this embodiment the integrity of the 'double helix structure is enhanced by at least one and preferably two chemical bonds. Chemical bonding can be achieved by any of a variety of well known techniques, for example by introducing covalent bonds, ionic bonds or hydrogen bonds; hydrophobic interactions, van der Waals or stacking interactions, by means of metals - Ion coordination; or via the use of an anthraquinone analog. The chemical group which can be used to modify the dsRNA preferably includes, but is not limited to, methylene blue; a difunctional group, preferably bis(2·chloroethyl)amine; N-ethinyl-N, (for acetaldehyde oxime) Benzobenzamide) cystamine; 4-thiouracil; and psoralen φ (Psoralen). In a preferred embodiment, the linker is a hexaethylene glycol linker. In this case, dsRNA is produced by solid phase synthesis and the hexaethylol linker is incorporated according to standard methods (e.g., Williams, D.J. and K.B. Hall, 〇c/zew. (1996) 35.14665-14670). In a particular embodiment, the 5' end of the antisense strand and the 3' end of the sense strand are chemically linked via a hexaethylene glycol linker. In another embodiment, at least one of the cores of the dsRNA comprises a thiochaic acid or a thioglycolic acid. The chemical bond at the end of the dsRNA is preferably formed via a triple helix bond. In certain embodiments, a 'chemical bond can be formed by means of one or more bonding groups 152219.doc -27-201130494' wherein the bonding group is preferably poly(oxyphosphinyloxy) 1,3 -propanol) bond and / or polyethylene glycol bond. In other embodiments, a ruthenium analog may be used instead of ruthenium to introduce a double bond structure to form a chemical bond. In other embodiments, azabenzene units can be introduced into the double strand structure to form a chemical bond. In other embodiments, a branched nucleotide analog can be used instead of a nucleotide acid to introduce a double bond structure to form a chemical bond. In certain embodiments, the chemical bond can be induced by ultraviolet light. In another embodiment, one or both of the two single strands may be modified to prevent or inhibit activation of cellular enzymes (e. g., certain nucleases). Techniques for inhibiting cellular enzyme activation are known in the art, including, but not limited to, 2,-amino modification, 2'-amino sugar modification, 2,-F sugar modification, 2,-F modification. Method, 2'-alkyl sugar modification method, uncharged main chain modification method, N_morpholinyl modification method, 2'-fluorene-fluorenyl modification method and amino phosphate (see, for example, 牦(10)匕(1995) 1:1116-8). Thus, at least one of the 2'-hydroxyl groups of the nucleotides on the dsRNA is replaced by a chemical group, preferably via a 2,-amino group or a 2,-methyl group. In addition, at least one nucleotide can be modified to form a locked nucleotide. This locked nucleotide contains a methylene bridge linking the 2'-oxygen of the ribose to the 4ι·carbon of the ribose. Introduction of the locked nucleotide into the oligonucleotide will improve the affinity for the complementary sequence and increase the melting temperature by several degrees. Modification of the dsRNA molecules provided herein can positively affect its in vivo and in vitro stability' and also improve its delivery to the (sick) target side. In addition, such structural and chemical modifications can positively affect the physiological response of the molecule after administration, such as the release of a preferably inhibited cytokine. Such chemistries and mouthwash modifications are known in the art and are specifically described in 152219.doc -28· 201130494 (2006) Current Topics in Med Chem, 6, 9 1 3-925. Binding a ligand to a dsRNA enhances its cellular uptake and targeting of specific tissues. In some cases, binding a hydrophobic ligand to a dsRNA helps direct cell membrane penetration. Alternatively, the ligand bound to the dsRNA is a receptor-mediated endocytosis effector. These methods have been used to promote cell penetration of antisense oligonucleotides. For example, cholesterol has been conjugated to a variety of antisense oligonucleotides to produce compounds that are substantially more active than their non-binding analogs. See M. Manoharan & iVwc/eic dcic?

Drwg 2002, 72, 103. Other lipophilic compounds that have been incorporated into oligonucleotides include 1-indolic acid, 1,3-bis-O-(hexadecyl)glycerol, and menthol. An example of a ligand for receptor-mediated endocytosis is folic acid. Folic acid enters cells by folate receptor-mediated endocytosis. The dsRNA compound with folic acid will be efficiently transported into the cell via folate receptor-mediated endocytosis. Attachment of folic acid to the 3' end of the oligonucleotide increases cellular uptake of the oligonucleotide (Li, S.; Deshmukh, Η. M.; Huang, L. Λα. 1998, 75, 1540). Other ligands that have been conjugated to the oligonucleotide include polyethylene glycol, carbohydrate errors, crosslinkers, conjugates, and delivery peptides. In some cases, binding of a cationic ligand to an oligonucleotide often improves resistance to nucleases. Representative examples of cationic ligands are propyl ammonium and dimercaptopropyl ammonium. It is noteworthy that antisense oligonucleotides have been reported to retain their high binding affinity for mRNA when the cationic ligand is dispersed throughout the oligonucleotide. See M. Manoharan Jwibe like e ά dcz’c? Drwg 2002, /2, 103 and references therein. 152219.doc -29- 201130494 The ligand-binding dsRNA of the present invention can be synthesized by using a dsRNA having a lateral reactive functional group such as a dsRNA obtained by ligating a ligation molecule to a dsRNA. The reactive oligonucleotide can be directly reacted with a commercially available ligand, a ligand synthesized with any of a plurality of protecting groups, or a ligand to which a linking moiety is attached. The method of the present invention facilitates the synthesis of ligand-bound dsRNA in some preferred embodiments by using a nucleoside monomer that has been properly bound to the ligand and can be further attached to a solid fulcrum material. These ligands, which are optionally linked to a solid support material, are nucleoside conjugates according to some preferred embodiments of the methods of the invention, via a selected serum binding ligand to a nucleoside or oligonucleotide 5, The linking moiety of the position is reacted to prepare. In some cases, a dsRNA with an aryl group attached to the 3' end of the dsRNA is covalently attached to the controlled microporous glass via a long chain amine group by first structuring the monomer building block. Support to prepare. The nucleotides are then bonded to the monomer building blocks bonded to the solid support via standard solid phase synthesis techniques. The monomer building block can be a nuclear bud or other organic compound that is compatible with solid phase synthesis. The dsRNA used in the conjugates of the invention may be suitably and routinely prepared by well known solid phase synthesis techniques. It is also known to use similar techniques to prepare other oligonucleotides such as phosphorothioates and alkylated derivatives. The teachings of the synthesis of specific modified oligonucleotides can be found in the following U.S. Patent No. 5,218,105, focusing on polyamine-binding oligonucleotides; U.S. Patent No. 5,541,307, which is incorporated herein by reference. Oligonucleotides of the main chain; U.S. Patent No. 5,521,302, which is directed to the preparation of an oligonucleotide having a palm-shaped glass bond; U.S. Patent No. 5,539,082, focusing on 152,219.doc • 30·201130494 Peptide Nucleic Acid U.S. Patent No. 5,554,746, the disclosure of which is incorporated herein by reference to U.S. Patent No. 5,571,9, the disclosure of which is incorporated herein by reference. Concerned about nucleosides having an alkylthio group, wherein such groups can be used as a linker to other moieties at any of a plurality of positions of the nucleoside; U.S. Patent No. 5,587,361, which is directed to having a high pair Oligonucleotides of palm-purity phosphorothioate linkages; U.S. Patent No. 5,5,6,351, which is directed to the preparation of 2,-nonane-cyclo-guanosine and related compounds (including 2,6-diamino groups) Method of hydrazine compound); Patent No. 5,587,469, which is directed to oligonucleotides having a Ν_2 substitution enthalpy; U.S. Patent No. 5,587,47, which is directed to oligonucleotides having 3-deazapurine; U.S. Patent No. 5,6,8 , 〇 46, focusing on the combination of 4-demethyl nucleoside analogs; U.S. Patent No. 5,61, 289, focusing on oligonucleotide modifications of backbone linkages; U.S. Patent No. 6,262,241, Particular attention is paid to the method of synthesizing 2,-fluoro-nucleotides. In the ligand-binding nucleoside ligand-binding φ dsRNA and ligand molecule of the present invention, a standard nucleotide or nuclear precursor, or a nucleotide or a nucleus having a linking moiety can be used. a glycoconjugate precursor, a ligand-nucleotide or nucleoside conjugate precursor that already carries a ligand molecule, or a construct with a non-nuclear ligand, on a suitable DNa synthesizer Singing oligonucleotides and collecting nuclear bitterness. When a nucleotide conjugate precursor that already has a linking moiety is used, it is generally & sequence-specifically linked to the synthesis of the nucleoside, followed by reacting the ligand molecule with the linking moiety to form a ligand-binding oligonucleotide . Oligonucleotide conjugates with a variety of molecules such as steroids, vitamins, lipids, and reporter molecules 1522l9.doc 201130494

Described (see Manoharan et al., PCT Application WO 93/07883). In a preferred embodiment, the oligonucleotide of the present invention or the flavonoid is used by an automated synthesizer to use an aminophosphorus gl g derived from a ligand-nucleoside junction (ph( Dsph (4) _, as well as the commercial amino acid vinegar to synthesize. Incorporate 2,-0-methyl, 2·-〇_ethyl, 2,-〇-propyl 2 in the nucleoside of the oligonucleotide 〇-allyl, 2'-fluorenylaminoalkyl or 2'-deoxy-2,-fluorine confers enhanced hybridization properties to oligonucleoside acid. In addition, oligonucleosides containing thiolate acid g-primary bond The acid has enhanced nuclease stability. Thus, the functionalized linked nucleosides of the invention can be enhanced to include either or both phosphorothioate backbones or 2'-0. fluorenyl, 2'- 〇 B Base, 2,-〇-propyl, 2,-nonylaminoalkyl, 2·〇〇 浠propyl or 2'-deoxy-2·-fluoro. In some preferred embodiments, DNA synthesis is used. The functionalized nucleoside sequence of the invention having an amine group at the 5' end is then reacted with an active vinegar derivative of the selected ligand. Active ester derivatives are well known to those skilled in the art. Ester includes hydrazine-hydroxybutylidene imide, Tetrafluorophenolate, pentafluorophenolate and pentaphenol ester. The reaction of an amine group with an active ester produces an oligonucleotide in which the selected coordination system is linked to the 5 position via a linking group. Prepared using a 5'-amine-based modifier C6 reagent. In a preferred embodiment, 'coordination-nucleoside-based group can be indirectly attached to the 5--yl group by using a ligand directly or via a linker Citrate, which binds the ligand molecule to the 5' position of the oligonucleotide. These ligand-nucleoside amine esterates are typically used at the end of an automated synthesis procedure to provide a 5' end with coordination The ligand of the ligand binds to the oligonucleotide. 152219.doc -32- 201130494 In a preferred embodiment of the method of the invention, the preparation of the ligand binding oligonucleotide is selected to construct a ligand molecule. Starting with a suitable precursor molecule. The precursor is typically a suitably protected derivative of a common nucleoside. For example, synthetic precursors for the synthesis of a ligand-binding oligonucleotide of the invention include, but are not limited to, 2,- Aminoalkoxy_5,_0DMT_nucleoside, 2|·6 aminoalkylamino-5-ODMT-nucleoside, 5'- 6-Aminoalkoxy deoxynucleoside, 51-6-aminoalkoxy-2-protected nucleoside, 3,_6-aminoalkoxy_5,_φ 〇DMT_nucleoside and 3'-Aminoalkylamino-5'-ODMT-nucleosides, which can be protected in the nucle〇 base portion of the molecule. Synthesis of these protected amine-linked protected nucleoside precursors Methods for bulk are known to those of ordinary skill. In many cases, a protecting group is used during the preparation of a compound of the invention. As used herein, the term "protected" means that a protecting moiety is attached to a specified moiety. In some preferred embodiments, the compound contains one or more sulfonyl groups. A wide variety of protecting groups can be used in the methods of the invention. In general, a protecting group promotes the chemical functional group to be inert to a particular reaction condition, and such functional groups that can be attached to the molecule and removed from such functional groups do not substantially impair the remainder of the molecule. Representative hydroxy protecting groups and other representative protecting groups are disclosed in Greene and Wuts, iVoieciive GVowps in Organic Sywihe Ws, Chapter 2, 2nd Edition, John Wiley & Sons, New York, 1991, and J Jpproac/z, Ekstein, F. ed., IRL Press, NY, 1991. The base treatment is used to selectively remove the acid-protected amino-protecting group and to allow the reactive amine group to be selectively used for the substitution. Examples of such groups 152219.doc •33· 201130494 for Fmoc (E. Atherton and R. C. Sheppard, 77ze S.

Udenfriend, J. Meienhofer, ed., Academic Press, Orlando, 1987, vol. 9, p. 1) and various substituted sulfonyl carbazate (exemplified by Nsc groups) (Samukov et al., Leii., 1994, 35:7821) Other amine protecting groups include, but are not limited to, carbamate protecting groups such as 2-trimethyldecyl ethoxycarbonyl (Teoc), methyl 丨 丨 (4_ 联Phenyl)ethoxycarbonyl (Bpoc), third butoxycarbonyl (B〇c), allyloxycarbonyl (Alloc), 9-fluorenylmethoxycarbonyl (Fmoc) and benzyloxycarbonyl (Cbz); Protecting group 'such as formazan, ethyl fluorenyl, tridentyl ethenyl, benzhydryl, and schwolyl phenyl acetoxy; decylamine protecting group 'such as 2-toluene thiol' and imine And cyclic quinone imine protecting groups such as phthaliminium and dithiabutadienyl. The equivalents of such amine protecting groups are also encompassed by the compounds and methods of the invention. Many solid supports are commercially available and the average builder can readily select the solid support to be used in the solid phase synthesis step. In some embodiments, a universal support is used. A universal support allows the preparation of nucleotides with unusual or modified nucleotides located at the 3' end of the oligonucleotide. For more details on the general support, see Scott et al., /w〇v buckle 〇 〇 户 in in solid-phase Synthesis, the 3rd international seminar, l99A, long

Edited by Epton, Mayflower Worldwide, 115-124. In addition, it has been reported that when an oligonucleotide is bonded to a solid branch via a relatively easy basic hydrolysis, the oligo(tetra) acid can be subjected to milder reaction conditions. Cracking from the common rammed material. See Guzaev, A"; M_h, Μ 152219.doc -34- 201130494 ·/. Jm. CT^e. Soc. 2003, 725, 2380. Nucleosides are linked by covalent bonds between phosphate-containing or phosphorus-free internucleosides. For the purposes of identification, such binding nucleosides can be characterized as nucleoside or ligand-nucleoside conjugates with a ligand. A linked nuclear bud having an aralkyl ligand and a nucleoside bound within its sequence will exhibit enhanced dsRNA activity compared to an unbound dsRNA compound. The aryl-ligand-binding nucleotide of the present invention also includes a combination of oligo-picuric acid φ and a nucleoside, wherein the ligand is directly linked to a nucleoside or a nucleoside •*• with no linker in between group. Preferably, the ligand is attached to the sulfhydryl, amine or pendant oxy group (0X0) of the ligand via a linking group. A typical linking group can be a hydroxy, guanamine or urethane group. Specific examples of preferred modified oligonucleotides contemplated for use in the ligand binding oligonucleotides of the invention include oligonucleotides comprising a modified backbone or a non-native nuclear interprotocol, as defined herein, Oligonucleotides having a modified backbone or internucleoside linkages include oligonucleotides that retain a phosphorus atom in the backbone and oligonucleotides that do not have a phosphorus atom in the backbone. For the purposes of the present invention, modified oligonucleotides having no phosphorus atom in the intersugar backbone can also be considered as oligonucleosides. Specific oligonucleotide chemical modifications are described below. All positions in a given compound are not necessarily uniformly modified. Conversely, more than one modification can be incorporated into a single dsRNA compound or even a single nucleotide thereof. Preferred modified internucleoside linkages or primary slits include, for example, thiolates, palmitic phosphorothioates, dithiophosphates, phosphotriesters, aminoalkyl diphosphates, methyl phosphonates And other alkyl phosphonates (including 3'-alkylene phosphonates and 1522l9.doc •35-201130494 for palmitic phosphonates), phosphonites, amino phosphates (including 3,-amino-amines) Phosphate and aminoalkyl-amino phosphate), thiocarbonylamino phosphate, thiosyl sulphuric acid vinegar, thiol sulphuric acid triacetate, and having a normal 3i_5' bond Boranophosphate, its 2'-5' linkage analog, and a borane phosphate having a reverse polarity (wherein adjacent nucleoside unit pairs are 3,_5, attached to 5'-3' or 2'-5' is connected to 5'-2'). Also included are various salts, mixed salts and free acid forms. The teachings of preparing the above phosphorus atom-containing bonds are well known in the art. Preferred (i.e., oligonucleoside) does not include a preferred modified internucleoside linkage or primary bond of a phosphorus atom having a short chain alkyl or cycloalkyl reactive sugar linkage, a mixed heteroatom, and an alkyl or cycloalkyl interactive sugar linkage. Or a backbone formed by one or more short chain heteroatoms or heterocyclic interaction sugar linkages. These backbones include a backbone having an N-morpholinyl bond (partially formed from a nucleoside sugar moiety); a siloxane base; a sulfide, a sulfoxide, and a sulfone backbone; Ermacetyl) and thioformamidine primary bond 'methylene methyl sulfonium thiol and thioindole primary bond; main chain containing dilute hydrocarbon, amino sulfonate backbone; mercapto imine And methylene fluorenyl backbone; sulfonate and sulfonamide backbone; guanamine backbone; and other backbones having a mixture of N, 〇, S and CH2 components. Representative U.S. patents for the preparation of the above-described oligonucleosides include, but are not limited to, U.S. Patent Nos. 5,034,506, 5,214,134, 5,216,141, 5,264,562, 5,466,677, 5,470,967, 5' Nos. 489,677, 5,602, 24, and 5,663, 312, each of which is incorporated herein by reference. In other preferred oligonucleotide mimetics, the nucleoside unit saccharide and nucleoside 152219.doc -36·201130494 bond (i.e., the backbone) are each replaced with a novel group. The nucleobase unit remains hybridized to the appropriate nucleic acid labeled dry compound. One such nucleus nucleotide (oligonucleotide mimetic) that has been shown to have excellent hybridization properties is called a peptide nucleic acid (PNa). In the pNA compound, the sugar backbone of the 'oligonucleotide is replaced by a main chain containing a decylamine, in particular an aminoethylglycine backbone. The nucleobase is retained and directly or indirectly bonded to the atom of the amine portion of the backbone. The teachings of PN a compounds can be found, for example, in U.S. Patent No. 5,539,082. • Some preferred embodiments of the invention employ oligonucleotides having phosphorothioate linkages and oligonucleotides having a hetero atom backbone, and in particular, U.S. Patent No. 5,4,9,677, mentioned above -CH2--NH--0--CH2--, -CH2- -Μ((:Η3)--0··(:Η2--[called methylene (methylimido) ) or mmi backbone], --CH2--〇-n(CH3)--CH2--, --CH2--N(CH3)--N(CH3)--CH2-- ' and an O-WCH ^-CHfCHf [wherein the natural phosphodiester backbone is represented by an OP-O-CH2.-], and the amidamide backbone of the above-mentioned U.S. Patent No. 5,602,240. The above-mentioned U.S. Patent No. φ 5,034,506 Oligonucleotides of the N-morpholinyl backbone structure are also preferred. The oligonucleotides used in the ligand-binding oligonucleotides of the present invention may or alternatively comprise nucleobases (in the art) Often referred to as "base" modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine base thymidine. (T), cytosine (C) and uracil. Modified nucleobases including other synthetic nuclei And natural nucleobases, such as 5-methylcytosine (5_me_c); 5-hydroxymethylcytosine; astragalus; hypoxanthine; 2-aminoadenine; adenine and guanine 6-methyl And other alkyl derivatives; adenine and guanine 152219.doc -37· 201130494 2 -propyl and other alkyl derivatives; 2 - sulfur spread bite, 2 - sulfur chest beta bite and 2-thiol 'Bite; 5-dentyl uracil and cytosine; 5-propargyl uracil and cytosine; 6-azouracil, cytosine and thymidine; 5- uracil (pseudo-pyrimidine); 4- Thiouracil; 8-dentyl, 8-amino, 8-mercapto, 8-sulfanyl, 8-hydroxy and other 8-substituted adenines and guanine; base (especially 5_bromo), 5-di Fluorine 1 methyl and other 5-substituted urinary sputum and sputum sputum; 7-methyl guanine and 7-mercapto adenine; 8 azaguanine and 8 azadenine; 7- Denitrifying guanine and 7-deaza adenine; and 3_deazaguanine and 3_deaza adenine. Other assays include those disclosed in U.S. Patent No. 3,687,808; Concise Encyclopedia Of Polymer Science And Engineering, Pages 858-859 'K Roschwitz, JI, ed., John Wiley &amp; s〇ns, 1990; Englsch et al., 1991, 30, 613; &amp; Sanghvi, YS, Chapter 15, Antisense Research and Applicati〇ns, Pp. 289-302, 'Croke, ST and Lebleu, B. ed., CRC Press, 1993. Some of these nucleobases are particularly useful for increasing the binding affinity of the oligonucleotides of the invention. Such nucleobases include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted oximes, including 2-aminopropyl adenine, 5-propargyl uridine Cyclic pyridine and 5-propargyl cytosine 5 -methylcytosine substitutions have been shown to increase the stability of the nucleic acid duplexes 〇6_丨2 (ibid., pp. 276-278), and are currently preferred bases The substitution, especially when combined with the 2, methoxyethyl sugar modification. Representative U.S. patents for the preparation of certain of the above-described modified nucleobases, as well as other modified nucleobases, 152, 219. doc, </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; No. 6, pp. 5, 459, 255, 5, 552, 540, 5, 594, 121, and 5, 596, 091, each of which is incorporated herein by reference. In certain embodiments, oligonucleotides used in the ligand binding oligonucleotides of the invention may or alternatively comprise one or more substituted sugar moieties. Preferred nucleotides comprise one of the following at the 2' position: 〇H; f; 〇-, S- or N-alkyl '0-, S- or N-alkenyl' or 〇, S^N_ alkyne a group wherein the alkyl group, the alkenyl group and the alkynyl group may be substituted or unsubstituted (: 1 to (: 1 () alkyl or c 2 to Ci alkenyl and alkynyl. More preferably 〇 [(CH 2 ) N〇]mCH3, 〇(CH2)n〇CH3, 0(CH2)nNH2, 0(CH2)nCH3, 〇(CH2)n〇qing and 〇(CH2)nON[(CH2)nCH3)]2, where n and m is from 1 to about i. Other preferred nucleotides include at one of the following positions: Ci to lower alkyl, substituted lower alkyl, alkaryl, aralkyl, decane-alkane Aryl or 〇-aralkyl, SH, SCH3, 〇CN,

Cl, Br, CN, CF3, 〇cf3, SOCH3, S02CH3, ON〇2, N〇2, N3, NH2, heterocycloalkyl, heterocycloalkylaryl, aminoalkylamino, polyalkylene Substituted sulphuric acid, RNA cleavage group, reporter group, sputum agent, group for improving the pharmacokinetic properties of oligonucleotide or for improving the pharmacodynamics of oligocore (4) a group, and other substituents having similar properties. Preferred modifications include 2••methoxyethoxy[2,_〇-CH2CH2OCH3, also a stalk of 2, _〇·(2·methoxyethyl) or 2·Μ〇Ε], ie, oxygenated Alkoxy groups. In addition, the preferred one includes 2,-dimethylaminooxyethoxy', that is, 0(CH2)2〇N(CH3)2 base]υ, also known as 2,_dMA〇e, as in 1998 1 The contents of the 152, 219, doc, pp. 39-201130494 patent are incorporated herein by reference. Other preferred modifications include 2,-methoxy (2'-fluorene--CH3), 2,-aminopropoxy U'-〇CH2CH2CH2NH2) and 2'-fluoro(2,-F) may also be Other positions on the nucleotides, particularly 3, terminal nucleotides or 2,_5, 3' positions of the sugars in the ligated oligonucleotide are similarly modified. As used herein, the term "sugar substituent" or "2" "-Substituent" includes a group attached to the 2,_ position of the ribofuranosyl moiety in the presence or absence of an oxygen atom. The sugar substituents include, but are not limited to, fluorine, hydrazine, alkyl, decane Alkylamino, 0-alkylalkoxy, protected oxime-alkylamino, hydrazine-alkylamino-based, 0-alkylimidazole, and a polyether of the formula (〇-alkyl)m, Wherein 111 is from 1 to about 10. Preferred of these polyethers are linear and cyclic polyethylene glycols (peg) and groups containing (PEG), such as crown ethers and especially Delgard® et al. (&gt; Reviews in Therapeutic Drug Carrier Systems 1992, 9: 249) The disclosure of the document is hereby incorporated by reference in its entirety. Other sugar modifications are disclosed in 1991, 6: 585-607. Fluorine, 0-alkyl, 〇-alkylamino group, 〇- Alkyl imidazole, hydrazine-alkylaminoalkyl, and alkylamino substituted are described in U.S. Patent No. 6,166,197, entitled "Oligomeric Compounds having Pyrimidine Nucleotide(s) with 2 and 5' Substitutions, which </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; Or alkynyl. 2'-SR nucleosides are disclosed in U.S. Patent No. 5,670,633, the disclosure of which is hereby incorporated by reference in its entirety. It is disclosed by Hamm et al. ("/C/zem., 1997, 62: 3415-3420). 2'-NR nuclear bud system by Goettingen, M., "/· C/2ew·, 1996, 61, 6273 -6281; and Polushin et al. 'Teira/zec/row Ze&quot;., 1996, 37, 3227-3230. Other representative examples suitable for use in the present invention include substituents having one of Formula I or Formula II group:

II wherein £ is &lt;31-&lt;:1(), N(Q3)(Q4) or N=C(Q3)(Q4); each Q3 and (^4 are independently Η, CrCM alkyl a dialkylaminoalkyl group, a nitrogen protecting group, a tethered or unconjugated binding group, a linker to a solid support; or Q3 and Q4 together forming at least one selected from the group consisting of N and optionally a nitrogen protecting group or a ring structure of other heteroatoms; qi is an integer from 1 to ίο; h is an integer from 1 to 1 ;; q3 is 〇 or 1; η is 0, 1 or 2; each, Ζ2 and Ζ3 are independent The ground is eve? cycloalkyl, C5_Ci4 aryl or C3_C丨5 hetero-l base' wherein the hetero atom in the heterocyclic group is selected from the group consisting of oxygen, nitrogen and sulfur; SM1 or Ν(Μι)2; Independently H, Ci_c^ 152219.doc -41- 201130494 base, C1-C8 haloalkyl, C(=NH)N(H)M2, c(=o)n(h)m2 or 0C(=0) N(H)M2 ; M2 is an alkyl group; and z5 is CVC10 alkylalkyl group, c2-c10 alkenyl group, (: 2-(:10 alkynyl group, c6-c14 aryl group, N(Q3)(Q4), 〇Q3, halo, SQ3 or CN. A representative 2,-0-saccharide substituent of formula I is disclosed in the title "Capped 2'-

U.S. Patent No. 6,172,209, the disclosure of which is incorporated herein in its entirety by reference. A representative cyclic 2-0-saccharide substituent of the formula 揭示 is disclosed in U.S. Patent No. 6,271,358, the entire disclosure of which is incorporated herein by reference. The saccharide-substituted sugars on the ribosyl ring are also suitable for use in the present invention. Representative substitutions of the anthracene ring include, but are not limited to, s, CH2, CHF, and CF2. The oligonucleotide may also have a moiety such as a cyclobutyl group. A pseudo-like alternative to pentofuranosyl sugar. Representative US patents for the preparation of such modified sugars include, but are not limited to, U.S. Patent Nos. 5,359, No. 44, No. 5,466,786, No. 5,519,134 And 5, 591, 722, 5, 597, 909, 5, 646, 265, and 5,700, 92, each of which is incorporated herein by reference. Other modifications are made to the 3' position of the sugar on the terminal nucleotide. For example, one other modification of the ligand binding oligonucleotide of the invention comprises the activity, cell distribution or Other non-ligand moieties or conjugates taken up by the cell are chemically linked to the oligonucleotide. These moieties include, but are not limited to, the lipid moiety 152219.doc -42 · 201130494 points, such as the cholesterol moiety (Letsinger et al., /&gt) ;〇〇.#如/.』〇£1&lt;^· &lt;SW. USA,1989,86,6553); Cholic acid (Manoharan et al,

Med. C/zew. Zeii·, 1994, 4, 1053); thioethers such as hexyl-S-tris-methyl mercaptan (Manoharan et al, NY Acad. Sci., 1992, 660, 306; Manoharan ^ A 5 Bioorg. Med. Chem. Let., 1993, 3, 2765); thiocholesterol (Oberhauser et al., and es., 1992, 20, 533); aliphatic chains such as dodecanediol or undecane Base residues (Saison-Behmoaras et al., EMBO J., 1991, 10, 111;

Kabanov^ A » FEBS Lett., 1990, 259, 327 ·, Svinarchuk et al, 5ioc/ziwz'e, 1993, 75, 49); linoleum, such as di-hexadecyl-racemic-glycerol or 1 , 2-di-indole-hexadecyl-racemic-glyceryl-3-H-phosphonic acid triethyl Ian (Manoharan et al, reiro/zec/ro) Zeii., 1995, 36, 3651; Shea^ A &gt; Nucl. Acids Res., 1990, 18, 3777); Polyamine or Polyethylene Glycol Bond (Manoharan et al, jVwc/eodi/t t: TV'wc/eonWa, 1995, 14, 969) Or adamantane acetic acid (Manoharan et al., 7Wra/ie &lt;ircm JLeii., 1995, 36, 365 1); brown paste base (Mishra et al., less i. Jcria, 1995, 1264, 229); Alkylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., */. Pharmacol. Exp. Ther., \996, 2ΊΊ, 923. The invention also encompasses the use of specific A composition that is substantially pure to a palm pure oligonucleotide. Examples of substantially pure palmitic nucleotides include, but are not limited to, oligonucleotides having at least 75% Sp or Rp phosphorothioate linkages. Nucleotides (Cook et al., U.S. Patent No. 5,587,361 And an oligonucleotide having an alkylphosphonate, an amino phosphate or a phosphorus 152219.doc.43-201130494 acid triester bond substantially free of palmar pure (Sp or Rp) (Cook, U.S. Patent No. 5,212,295 And No. 5,521,302). In some cases, the oligonucleotide may be modified by a non-ligand group. Many non-ligand molecules have been bound to the oligonucleotide to enhance the activity of the oligonucleotide, Cell distribution or cellular uptake, and procedures for performing such binding are available in the scientific literature. These non-ligand moieties include lipid moieties such as cholesterol (Letsinger et al., /Voc. iVa&quot;. &lt;SW.t/ SJ, 1989, 86: 6553); Cholic acid (Manoharan et al, Med Chem. Lett., 1994, 4: 1053); thioethers such as hexyl-S-trityl mercaptan (Manoharan et al., /4) ««. See; K *Scr/., 1992, 660: 306; Manoharan et al., Mec/. CAew. Lei, 1993, 3: 2765); thiocholesterol (Oberhauser et al., iVwc/. Λα., 1992, 20: 533); aliphatic bonds, such as dodecadiol or hydrazine-based residues (Saison-Behmoaras et al, 1991, 10: 111; Kabanov et al, le &quot;., 1990, 259:32 7 ; Svinarchuk et al, 5ioc/nm/e, 1993, 75:49); phospholipids, such as di-hexadecyl-racemic-glycerol or 1,2-di-O-hexa-system-external Triethyl glycerol-3-H-phosphonate (Manoharan et al, Tetrahedron Lett., 1995, 36:3651; Shea et al, Nucl. ylc/heart es., 1990, 18: 3777); Polyamine or polyethylene glycol chain (Manoharan et al, c&amp; TVwc/eonWe?, 1995, 14: 969); or diamond acetal (Manoharan et al, Tetrahedron Lett., 1995, 36: 3651); palm base Part (Mishra et al., price, dcia, 1995, 1264: 229); or octadecylamine or hexylamino-carbonyl-oxycholesterol (Crooke et al., /. P/zarwoco/· JTzer ·, 152219.doc -44- 201130494 1996, 277: 923). A typical binding scheme involves the synthesis of an oligonucleotide having an amino linker at one or more positions in the sequence. The amine group is then reacted with the bound molecule using a suitable coupling or activating reagent. The binding reaction can be carried out using oligonucleotides still bound to the solid support or after the oligonucleotides are cleaved in the solution phase. Purification of oligonucleotide conjugates by HPLC typically results in a pure conjugate. Alternatively, the bound molecule can be converted to a building block such as amino sulphate via an alcohol group present in the molecule or by attachment of a linker with a phosphoric acidable alcohol group. It is important that each of these methods be used to synthesize a ligand binding oligonucleotide. The amine-linked oligonucleotide can be coupled directly to the ligand via the use of a coupling reagent or after activation of the ligand to NHS or pentafluorophenolate. The ligand amine carboxylic acid ester can be synthesized by attaching an aminohexanol linker to a slow group followed by phosphating the terminal alcohol functional group (ph〇sphitylati〇n). Other linkers such as cysteamine can also be used to bind to the chloroethyl hydrazide linker present on the synthetic oligonucleoside IgG. Those skilled in the art will readily appreciate methods for introducing molecules of the invention into cells, tissues or organisms. Corresponding examples have also been provided in the above detailed description of the invention. For example, a nucleic acid molecule or vector of the invention encoding at least one strand of a dsRNA of the invention can be introduced into a cell or tissue by methods known in the art (e.g., transfection, etc.). Means and methods for introducing dsRNA molecules have also been provided. By way of example, by glycosylation and folate-modified molecules (including the use of polymeric carriers with ligands, such as galactose and lactose) or by linking folic acid to 152219.doc •45-201130494 in various macromolecules Carrying out the dry direction allows the molecule to be delivered to bind to the acid acceptor. Targeted delivery of peptides and proteins other than antibodies is known, for example, including RGD-modified nanoparticles or multi-component (non-viral) delivery systems for the delivery of siRNA in vivo, including short cyclodextrins. , D Hyun-PEG. Further, it is also contemplated that (iv) dry delivery of antibodies or antibody fragments, including (monovalent) Fab fragments of antibodies (or other fragments of such antibodies) or single-chain antibodies. Injection methods for dry-labeled delivery include, inter alia, hydrodynamic intravenous injection. The cholesterol conjugate of dsRNA can also be used for targeted delivery, where binding to a lipophilic group enhances cellular uptake of the oligonucleotide and improves its pharmacokinetics and tissue biodistribution. Cationic delivery systems are also known in which a synthetic carrier having a net positive (cationic) charge facilitates complex formation with a polyanionic nucleic acid and interaction with a negatively charged cell membrane. Such cationic delivery systems also include cationic liposome delivery systems, cationic polymers, and peptide delivery systems. Another delivery system for cellular uptake of dsRNA/siRNA is aptamer-dsRNA/siRNA. Gene therapy methods can also be used to deliver a dsRNA molecule of the invention or a nucleic acid molecule encoding the same. Such systems include the use of non-pathogenic viruses, modified viral vectors, and delivery agents using nanoparticles or liposomes. Other delivery methods for cellular uptake of dsRNA are extracorporeal, such as ex vivo treatment of cells, organs or tissues. Some of these techniques are described and summarized in publications such as Akhtar (2007), Journal of Clinical Investigation 1 17, 3623-3632; Nguyen et al. (2008), Current Opinion in Moleculare

Therapeutics 10, 158-167; Zamboni (2005), Clin Cancer

Res 11, 8230-8234, or Ikeda et al. (2006), Pharmaceutical 152219.doc -46- 201130494

Research 23, 1631-1640. Unless otherwise stated, all the technical and scientific techniques used herein have the meaning commonly understood by those skilled in the art: meaning. Suitable methods and materials are described below, but methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All publications, patent applications, patents, and <RTIgt; </ RTI> references cited herein are hereby incorporated by reference in their entirety in their entirety in the extent of In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. The embodiments and entries of the invention provided above are now illustrated by the following non-limiting examples. [Embodiment] Example

Identification of dsRNAs for therapeutic use The dsRNA design is used to identify dsRNAs that specifically target human IL_丨8 for therapeutic use. First, the known mRNA sequence of human (smart) IL-18 (ΝΜ_001562·2, listed as SEQ ID NO. 783) was downloaded from NCBI Genbank. In the identification of RNAi agents, by using a proprietary algorithm, the selection is limited to 19-mer sequences with at least 2 mismatches relative to any other sequence in the human RefSeq database (28th edition), which we assume assumes extensive humans Transcriptome. The coding sequence (CDS) of the cynomolgus IL-18 gene was sequenced (see SEQ ID NO. 784) and the target region of the RNAi reagent was examined by computer analysis 152219.doc -47 - 201130494 domain. All sequences containing 4 or more consecutive Gs are excluded from the synthesis). The sequence thus identified serves as the basis for the synthesis of the reagents in Schedule 1 and Schedule 2. table! The relationship between the unmodified sequence shown in Table 2 and its modified counterpart in Table 2 is shown in Table 12. Λ Λ 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀 肀

Identification of the mouse-type dsRNA to IL-18 for the design of the collision to identify the specific dry to the mouse! The dsRNA of 8 is used for proof of concept. The known mRNA sequence of il_i8 from mouse (Mus musculus) in NCBI GenbankT (ΝΜ_〇〇836〇), listed as SEQ 〇 n〇785)° When using the proprietary algorithm, select the RNAi reagent It is limited to 19-mer sequences with at least 2 mismatches relative to any other sequence in the mouse Ref Seq database (28th edition), which we assume assumes a broad mouse transcriptome. All sequences containing 4 or more consecutive Gs (multi-G sequences) were excluded from the synthesis. The sequence thus identified became the basis for the synthesis of the RNAi reagents (dsRNAs cross-reactive with mouse IL-18) in Schedules 5 and 6. The relationship between the unmodified sequences shown in Table 5 and their modified counterparts in Table 6 is shown in Table 13. dsRNA Synthesis If a reagent source is not specifically provided herein, the reagent can be obtained from any supplier of molecular biology reagents according to the quality/purity criteria applied by Molecular Biology 152219.doc • 48-201130494.

By solid phase synthesis, on a scale of 1 μm, using Expedite 8909 synthesizer (Applied Biosystems, Applera Deutschland GmbH, Darmstadt, Germany) and controlled microporous glass (CPG, 500 A, Proligo Biochemie GmbH, Hamburg, Germany) as A solid support is used to prepare a single strand of RNA. By solid phase synthesis, the corresponding amino phosphate and amine based acid 2'-(9-methyl hydrazine (Proligo Biochemie GmbH, Hamburg, Germany) were used to generate RNA and contain 2'-0-fluorenyl nucleosides. Acid RNA. Use such as

Current protocols in nucleic acid chemistry, Beaucage, SL et al. (eds.), standard nucleoside phosphate phosphate chemistry as described in John Wiley &amp; Sons, Inc., New York, NY, USA. The segment is incorporated into a selected site within the sequence of the oligoribonucleotide chain. The phosphorothioate linkage was introduced by replacing the iodinated solution with an acetonitrile solution (1%) of Beaucage reagent (Chruachem Ltd, Glasgow, UK). Other auxiliary reagents were obtained from Mallinckrodt Baker (Griesheim, Germany). The protecting group of the crude oligoribonucleotide was removed according to the development procedure and purified by anion exchange HPLC. The yield and concentration were determined by UV absorption of individual RNA solutions at a wavelength of 260 nm using a spectrophotometer (DU 640B, Beckman Coulter GmbH, Unterschlei Bheim, Germany). The double-stranded RNA was generated by mixing the complementary equimolar molar solution in the binding buffer (20 mM sodium phosphate, pH 6.8; 100 mM sodium hydride), and heated in a water bath at 85-90 ° C for 3 minutes and Cool to room temperature over a period of 3-4 hours. The adhered RNA solution was stored at -20 °C until use. 152219.doc -49· 201130494 Activity assay of therapeutic dsRNA targeting IL-18 The activity against dsRNA of il-18 was tested in HCT-116 cells. IL-18 mRNA was quantified using branched DNA from total mRNA isolated from cells cultured using IL-18-specific dsRNA assay using HCT-116 cells in culture. HCT-116 cells were obtained from the American Type Culture Collection (Rockville, Md.; Cat. No. CCL-247) and in a moisture-containing incubator (Heraeus HERAcell, Kendro Laboratory)

Products, Langenselbold, Germany), supplemented with 10% fetal bovine serum (FCS) at 37 ° C in a 5% C〇2 atmosphere (Biochrom AG, Berlin, Germany; catalog number SOI 15), 2 mM L-glutamic acid (Biochrom AG, Berlin, Germany; Cat. No. K0283) and McUy's 5a medium of 100 U/ml penicillin, 1 〇〇mg/ml lentin (Biochrom AG, Berlin, Germany; Cat. No. A2213) Cultured in (Biochrom AG, Berlin, Germany; Cat. No. F 1015). DsRNA transfection was performed directly after inoculation of 20,000 cells/well in 96-well plates and was performed using Lipofectamine 2000 (Invitrogen GmbH, Karlsruhe, Germany; Cat. No. 11668-019) as described by the manufacturer. In two separate single-dose experiments performed in quadruplicate, dsRNA was transfected at a concentration of 50 nM. The characteristics of the most potent dsRNA against IL-18 from a single dose screen were further analyzed from the dose response curve. For the dose response curve, transfection was performed for the above single dose screen, but the initial concentration was 100 nM and the dilution was reduced to 10 fM at 6 fold. After transfection, the cells were incubated for 24 hours in a moisture-containing incubator (Heraeus GmbH, Hanau, Germany) at 37 ° C and 5% C 〇 2 152219.doc -50 - 201130494. To measure IL-18^ mRNA, cells were harvested and at 53. (: Follow the Quantise ExplQre kit (4) (10) to f,

CaHf·, USA; Catalog No. QG_4) The manufacturer lyses the cells for the procedure recommended by the company. Subsequently, 50 μιη lysate was incubated with a probe set specific for human iL]8 and 1Q μΐ lysate was incubated with probe set 1 specific for human GAPDH (probe group sequence see Schedule 8 and Schedule 9), and processed according to the manufacturer's plan for QuanUGene. The chemiluminescence was measured in RLU (relative light units) in ViCt〇r2-Light (Perkin Elmer, trade "(3), Germany), and the values obtained using the human _18 probe set were corrected to the respective wells. The GApDH values of each of the others were then correlated with the mean of the two unrelated control dsRNAs in the single dose 1 test. In the dose response experiments, the values obtained using specific siRNA were compared with mock transfection. (=Lip-dyeamine 2〇〇〇, no dsRNA) alignment correlation. Inhibition data is provided in Schedule 2 and Schedule 3. The activity of siRNA against murine IL_i8 was tested in RAW264.7 cells. Inhibition data was provided. Activity assay of dsRNA against dry mouse IL-18 was performed using RAW264.7 cells in culture from branched DNA in total mRNA isolated from cells cultured with murine IL-18-specific siRNA assays. Quantitative murine IL-18 mRNA. RAW264.7 cells were obtained from the American Type Culture Collection (Rockville, Md.; Cat. TIB-71) and in a moisture containing incubator (Heraeus HERAcell, Kendro Laboratory Products, Langenselbold, Germany) ), at 152219.doc -51 - 201130494 3 7 ° C, containing 50 / 〇 C 〇 2 atmosphere in the supplement containing 10 〇 / 〇 fetal bovine serum (FCS) (Biochrom AG, Berlin, Germany; catalog number S0115), 2 mM L-face valeric acid ( Biochrom AG, Berlin, Germany; catalog number K0283), 1 mM sodium citrate (Biochrom AG, Berlin, Germany; catalog number L0473) and 100 U/ml penicillin, 100 mg/ml telicomycin (Biochrom AG, Berlin, Germany; catalog number A2213) in DMEM (Biochrom AG, Berlin, Germany; Cat. No. F0435). About 16 hours before transfection, by adding interferon y to the cell culture medium (Sigma-Aldrich, Taufkirchen, Germany; No. 14777) reached a final concentration of 1 ng/ml to induce IL-1 8 expression. Directly transfected with siRNA at 20,000 cells/well in 96-well plates and using HiPerFect (Qiagen, Hilden) as described by the manufacturer , Germany; Cat. No. 301705). Transfected siRNA at a concentration of 5 〇 nM in two separate single-dose experiments in quadruplicate. Further characterization of murine IL-18 from single-dose screening by dose response curves The most effective siRNA. For the dose response curve, transfection was performed for the above single dose screen, but the initial concentration was 丨〇〇 nM and was diluted 6-fold to 1 〇 fM. After transfection, the cells were incubated for 24 hours at 37 ° C and 5% CO 2 in a moisture-containing incubator (Heraeus GmbH, Hanau, Germany). To measure murine il-18 mRNA, cells were harvested and following the manufacturer's Quantigene n Expl〇re kit (pan〇mics, Fremont, Calif., USA; catalog number QS99〇〇) at 53 °C for bDNA The recommended procedure dissolves cells. Subsequently, 50 μL of the lysate was incubated with a probe group specific for murine _18 and a 1 μl lysate was conjugated to a probe group specific for murine GAPDH. The sequence is shown in Schedule 152219.doc -52· 201130494 ι〇 and Schedule li) and processed according to the manufacturer's protocol for QuantiGene. Chemiluminescence was measured in RLU (relative light units) in Victor2-Light (Perkin Elmer, Wiesbader, Germany), and the values obtained using the human murine IL_j 8 probe set were corrected to each of the wells GAPDH Values were then correlated with the mean of three unrelated control siRNAs in a single dose experiment, whereas in dose response experiments, values obtained using specific siRNA were correlated with mock transfection (=HiPerFect, no siRNA). • Stability of dsRNA Human or mouse serum was used in an in vitro assay to determine the stability of dsRNA to human IL-18 by measuring the half-life of each individual strand. Samples of 3 μl 50 μΜ dsRNA mixed with 30 μΐ human serum (sigma) or mouse serum (Sigma) were used in triplicate for each time point. The mixture was incubated at 37 ° C for 30 minutes, 1 hour, 3 hours, 6 hours, 24 hours or 48 hours. As a control for non-specific degradation, &lt;^1^8 48 hours was incubated with 30卩11&lt;?88 (卩116.8). At 65. 〇φ下' terminated by adding 4 μ chymotrypsin K (20 mg/ml) ' 25 μΐ Tissue and Cell Lysis Solution (Epicentre) and 38 μM Millipore water over 30 minutes reaction. The sample was then spin-filtered through a 0.2 μιη 96-well filter plate at 1400 rpm for 8 minutes&apos; washed twice with 55 μM Millipore water and again rotary filtered. To separate the single strands and analyze the remaining full length product (FLp), the sample was passed through denaturing conditions using i 〇〇 /0 ACN (pH = 11) containing 20 mM Na3P04 as the eliminator A and the eliminator containing 1 M NaBr. a ion exchange Dionex Summit HPLC as solvate B 〇152219.doc -53- 201130494 Apply the following gradient: time %A %B -1.0 minutes 75 25 1.00 minutes 75 25 19.0 minutes 38 62 19.5 minutes 0 100 21.5 minutes 0 100 22.0 Minutes 75 25 24.0 minutes 75 25 For each injection, the chromatograms are automatically integrated by Dionex Chromeleon 6.60 HPLC software and manually adjusted if necessary. All peak areas were corrected for the internal standard (IS) peak and corrected for incubation at t = 0 minutes. The area under the peak and the remaining FLP of each single and triplicate samples were calculated separately. The average time point [hours] of one-half FLP degradation in triplicate samples is defined as the half-life (t1/2) of one strand. The results are provided in the attached Table 4. Cytokine induction The potential cytokine induction of dsRNA was determined by measuring the release of IFN-a and TNF-a in an in vitro PBMC assay. Human peripheral blood mononuclear cells (PBMC) were isolated from the white blood cells of both donors by Ficoll centrifugation on the day of transfection. Cells were transfected in quadruplicate with dsRNA and incubated for 24 hours at 37 °C using Gene Porter 2 (GP2) or DOTAP in Opti-MEM to a final concentration of 130 nM. It is known that dsRNA sequences that induce IFN-a and TNF-a in this assay, as well as CpG oligo, are used as positive controls. Chemically bound dsRNA or CpG oligonucleotides that do not require a transfection reagent for cytokine induction are cultured in culture medium at a concentration of 500 nM. At the end of the incubation, quadruplicate culture supernatants were collected 152219.doc -54- 201130494. IFN-a and TNF-a were then assayed in these pooled supernatants by standard sandwich ELISA with two data points per pool. A score of 0 to 5 (where 5 represents maximum induction) is used to indicate the degree of cytokine induction relative to the positive control. The results are provided in the attached Table 4. Inhibition of function by dsRNA The ability to target the dsRNA-mediated functional response of human IL-1 8 was determined in a cell-based in vitro assay. Functional reads are siRNA-induced inhibition of LPS-stimulated human IL-18 protein secretion in human macrophage cell line (THP-1). Transfection Briefly, siRNA against human IL-1 8 and control siRNA from dry to AHSA-1 were transfected into THP-1 cells using DharmaFECT l (Dharmacon, Inc.; Cat. No. T-2001-02). ATCC; catalog number TIB-202). The siRNA to human IL-18 and the control siRNA were complexed with φ DharmaFECT 1 at 10 nM for 20 minutes at room temperature. THP-1 cells were seeded at a cell density of 100,000 cells/well in RPMI 1640 (Invitrogen; Cat. No. 118750-93) + 0.5°/ in 96-well plates. Fetal bovine serum (Gemini; Cat. No. 100-106). The transfection mixture was added to the cells at 0.15 μΐ/well and incubated at 37 ° C for 48 hours (for mRNA analysis) or 66 hours (for IL-18 protein analysis). Complete medium was added 3 hours after transfection. mRNA analysis to measure mRNA, collect transfected THP-1 cells and follow the manufacturer's Quantigene II Explore kit at 65 °C (Panomics; Cat. No. 152219.doc -55- 201130494 QS9900) for bDNA recommendations The program lyses the cells. Subsequently, the lysate was incubated with a probe set specific for human IL-1 8 and actin and processed according to the manufacturer's protocol for Quantigene II. The values obtained using the human IL-18 probe set were corrected to each of the other human actin values obtained for each well, which in turn was associated with mock transfection (=DharmFECT 1, no siRNA). IL-18 protein analysis 48 hours after transfection 'The cells were treated with 1 pg/ml LPS (Sigma; Cat. No. L-6529) to induce IL-1 8 expression and secretion (Zeisel et al. (20〇4) Cell. Microbiol. 6: 593-598). Human culture supernatant was collected 18 hours after LPS treatment and human IL-1 8 was measured in the supernatant by standard sandwich ELISA (R&amp;D Systems; Cat. No. 7620). The concentration of human IL-1 8 protein was calibrated from the dose response curve based on the reference standard provided by the manufacturer. The amount of IL-18 mRNA in the siRNA-treated cells was calculated as the performance of the residual IL-18 mRNA compared to the mock-transfected cells. The amount of IL-1 8 protein secreted from the cells after LPS treatment is expressed in pg/mi. The results of functional assays for IL-1 8 protein secretion and mRNA inhibition are provided in Figure i. Inferred off-target IL-18 in vitro assays psiCHECKTM vector (Promega) contains two reporter genes for monitoring RNAi activity: sea Synthetic version of the renal luciferase (hRluc) gene and the synthetic firefly luciferase gene (hluc+). The firefly luciferase gene allows for the regulation of the expression of the luciferase by the firefly luciferase. Measurement of sea kidney and labor using the Dual-Glo® luciferase assay system (prornega) 152219.doc 56· 201130494 Firefly luciferase activity. To analyze the off-target effect of the dsRNA of the present invention using the psiCHECKTM vector, the predicted off-target sequences were cloned into multiple colonies located at 3 of the synthetic Renilla luciferase gene and its translation stop codon. After colonization, the vector is transfected into a mammalian cell line and subsequently co-transformed with a dsRNA targeting 18. If the dsRNA effectively elicits the RNAi process on the predicted RNA of the desiccant, then the fusion of the Renilla target gene 11111]^8 sequence will degrade&apos; to reduce the Renilla luciferase activity. φ Electron hybrid off-target prediction The sequence homologous to the dsRNA of the present invention in the human genome was searched by computer analysis. A homologous sequence showing less than 6 mismatches to the dsRNA of the invention is defined as a possible off-target. Desiccation selected for in vitro off-target analysis is provided in Schedule 14. Strategies for generating potential efflux effects of psiCHECK vectors containing predicted target off-target sequences for siRNA major candidates include colonization of predicted desiccization sites into the pSiCHECK2-loaded system via Xhol and Notl restriction sites (Dual Glo® system; Promega, Braunschweig) , Germany; Catalog No. C8021) Shen. Thus, the off-target site extends 1 nucleotide above the dsRNA target site and is followed by a sequence for selection. In addition, the Nhel restriction site was integrated to confirm fragment insertion by restriction analysis. Single-stranded oligonucleotides were ligated in Mastercycler (Eppendorf) according to standard protocols (eg, Metabion's protocol) and subsequently cloned into psiCHECK (Promega) previously digested with XhoI and Notl restriction enzymes (eg, New England Biolabs). Successful insertion was verified by restriction analysis with Nhel followed by sequencing of the positive pure lines. After the pure line is produced, it will be used in cell culture experiments. 152219.doc 57· 201130494 Analysis of cell culture in dsRNA: Cos7 cells were obtained from Deutsche Sammlung fiir Mikroorganismen und Zellkulturen (DSMZ, Braunschweig, Germany; Cat. No. ACC-60) and in a moisture-containing incubator (Heraeus HERAcell, Kendro Laboratory Products, Langenselbold, Germany) In a 37 ° C, 5% CO 2 atmosphere, supplemented with 10% fetal bovine serum (FCS) (Biochrom. AG, Berlin, Germany; catalog number S0115), 100 U / ml penicillin and 100 pg / Mol streptomycin (Biochrom AG, Berlin, Germany; Cat. No. A2213) and 2 mM L-face valeric acid (Biochrom AG, Berlin, Germany; Cat. No. K0283) and 12 pg/ml sodium bicarbonate DMEM (Biochrom AG , Berlin, Germany; catalog number F0435). Transfection and luciferase quantification: For transfection with plastids, Cos-7 cells were seeded at a density of 2.25 x 104 cells/well in 96-well plates and directly transfected. Plastid transfection was carried out using a lipofectamine 2 (Invitrogen GmbH, Karlsruhe, Germany; Cat. No. 11668-019) at a concentration of 50 Ng/孑1&gt; as described by the manufacturer. Four hours after transfection, the medium was discarded and fresh medium was added. The siRNA was now transfected with a lipofectamine 2000 as described above at a concentration of 50 nM. 24 hours after siRNA transfection, cells were lysed using the luciferase reagent described by the manufacturer (Dual-GloTM Luciferase Assay System; Promega, Mannheim, Germany; Cat. No. E2980) and the firefly was quantified according to the manufacturer's protocol. And Renilla luciferase. The content of the Renilla luciferase protein was corrected for the firefly luciferase content. For each siRNA, eight individual data points were collected from two independent experiments, 152219.doc • 58-201130494. siRNA, which was not associated with all target sites, was used as a control to determine the relative renilla luciferase protein content in siRNA-treated cells. All results of the transfection experiment are summarized in Table 16.

Endogenous analysis was performed using a single dose screen at 50 nM showing that the Renilla luciferase knockout exceeded 25% off-target. This was further characterized in a dose response curve with a 6-fold dilution to reduce the concentration range from 100 nM to 10 fM. Transfection was performed in human A431 cells using lipofectamine 2000 as described above. A43 1 cells were obtained from Deutsche Sammlung fiir Mikroorganismen und Zellkulturen (DSMZ, Braunschweig, Germany; Cat. No. ACC-9 1) and in a moisture-containing incubator (Heraeus HERAcell, Kendro Laboratory Products, Langenselbold, Germany) at 37° C. In a 5% C02 atmosphere, supplemented with 10% fetal bovine serum (FCS) (Biochrom AG, Berlin, Germany; catalog number S0115), 100 U/ml chlorophyll and 100 pg/ml Cultured in RPMI (Biochrom AG, Berlin, Germany; Cat. No. FG 1215) of (Biochrom AG, Berlin, Germany; Cat. No. A2213). After transfection, the cells were incubated for 24 hours at 37 ° C and 5% CO 2 in a moisture containing incubator (Heraeus GmbH, Hanau, Germany). To measure IL-18 mRNA and all off-target mRNA and GAPDH mRNA, the QuantiGene 2.0 assay kit for the bDNA quantification of mRNA (Panomics, Fremont, Calif., USA) was used. Transfected A431 cells were harvested and lysed at 53 °C following the manufacturer's recommended procedure. 50 μL of lysate with a probe set specific for human IL-18 (Table 26, SEQ ID No 1164-11 83) or specific off-target mRNA (probe sequence of the probe set see Table 18 to 152219.doc -59- 201130494 25, SEQ ID No 941-1163) - incubated and processed according to the manufacturer's protocol for QuantiGene. To measure GAPDH mRNA, 10 μΐ of cell lysate was analyzed using the GAPDH-specific probe set (Table 27, SEQ ID No 1184-1203). Chemiluminescence was measured in RLU (relative light units) in Victor2-Light (Perkin Elmer, Wiesbaden, Germany), and the values obtained using the human IL-18 or off-target probe set were corrected to the GAPDH values of each well. . Unrelated control siRNA was used as a negative control. All data on dose response experiments are provided in Schedule 17.

152219.doc 60- 201130494

Unit antisense sequence (5'-3 ·) UCGUUUUGAACAGUGAACA UUCGUUUUGAACAGUGAAC CUUCGUUUUGAACAGUGAA GAAAGUAUCCUUCGUAUGA CUUAUUAUCAUGUCCUGGG GCUAGUCUUCGUUUUGAAC UGGCUAUCUUUAUACAUAC CCGAUUUCCUUGGUCAAUG UCCUGCGACAAAUAGUUUG UGUUCUCACAGGAGAGAGU AAAGCGUAUUGUCAAUAAA AGUUUGUUGCGAGAGGAAG ACUUAUAAUAAAUAUGGUC AGGCCGAUUUCCUUGGUCA UAGCUAGUCUUCGUUUUGA CUUCGUAUGAUGAAGAUUC AACAUUAUAGAUCUAUCCC UUAUUCCUGCGACAAAUAG AGUCAUAUCUUCAAAUAGA UGCGACAAAUAGUUUGUUG UCCUUCGUAUGAUGAAGAU AAAUAGUUUGUUGCGAGAG UUCGUAUGAUGAAGAUUCA AAGCGAUCUGGAAGGUCUG UGCGAGAGGAAGCGAUCUG GUUACAGCCAUACCUCUAG AAGCGUAUUGUCAAUAAAU AUAAAGUAAAGCGUAUUGU GCUAGAAAGUAUCCUUCGU SEQ ID NO (N 〇〇〇 inch ( N inch OO 3 CN 00 o 5 OO sense shares sequence (5'-3 ') UGUUCACUGUUCAAAACGA GUUCACUGUUCAAAACGAA UUCACUGUUCAAAACGAAG UCAUACGAAGGAUACUUUC CCCAGGACAUGAUAAUAAG GUUCAAAACGAAGACUAGC GUAUGUAUAAAGAUAGCCA CAUUGACCAAGGAAAUCGG CAAACUAUUUGUCGCAGGA ACUCUCUCCUGUGAGAACA UUUAUUGACAAUACGCUUU CUUCCUCUCGCAACAAACU GACCAUAUUUAUUAUAAGU UGACCAAGGAAAUCGGCCU UCAAAACGAAGACUAGCUA GA AUCUUCAUCAUACGAAG GGGAUAGAUCUAUAAUGUU CUAUUUGUCGCAGGAAUAA UCUAUUUGAAGAUAUGACU CAACAAACUAUUUGUCGCA AUCUUCAUCAUACGAAGGA CUCUCGCAACAAACUAUUU UGAAUCUUCAUCAUACGAA CAGACCUUCCAGAUCGCUU CAGAUCGCUUCCUCUCGCA CUAGAGGUAUGGCUGUAAC AUUUAUUGACAAUACGCUU ACAAUACGCUUUACUUUAU ACGAAGGAUACUUUCUAGC Ο 2 Q σ ω in Bu square \ Bu Os (N 3 (N ON CN Os JO in iT) Bu 152219.doc s 201130494

Antisense shares sequence (5'-3 ·) UGCACUGGGAGACAAUUCC CCCGAAGCUGUGUAGACUG AAAGUAUCCUUCGUAUGAU UCGUAUGAUGAAGAUUCAA CGUAUGAUGAAGAUUCAAA GUUGCGAGAGGAAGCGAUC AUAGUUACAGCCAUACCUC UUAUUAUCAUGUCCUGGGA CUUCCCGAAGCUGUGUAGA CAAAUAGUUUGUUGCGAGA UCCGGAGUGCAAGUGAUUC GACUGAUAAUUUAGAUUCA GAUGUUAUCAGGAGGAUUC UAGUUACAGCCAUACCUCU UAUUAUCAUGUCCUGGGAC UUGUAUCCUUGAUGUUAUC CCUGCGACAAAUAGUUUGU CAAGCUAGAAAGUAUCCUU CCGGCAUGAAAUUUUAAUA CAUACCUCUAGGCUGGCUA UCUACUGGUUCAGCAGCCA CCGGAGUGCAAGUGAUUCU CCCGGCAUGAAAUUUUAAU CGAAGCUGUGUAGACUGCA ACAGUGAACAUUAUAGAUC CCGAAGCUGUGUAGACUGC GCCCGGCAUGAAAUUUUAA CUGCGACAAAUAGUUUGUU AGCGUAUUGUCAAUAAAUU GCGCCCGGCAUGAAAUUUU AGGGCAUGCGUCACUACAC Ο a α ω C / D 00 VO o CN VO oo § OO 00 OO OO 〇oo 〇〇〇 square inch (N shares sense sequence σ-3 ') GGAAUUGUCUCCCAGUGCA CAGUCUACACAGCUUCGGG AUCAUACGAAGGAUACUUU UUGAAUCUUCAUCAUACGA UUUGAAUCUUCAUCAUACG GAUCGCUUCCUCUCGCAAC GAGGUAUGGCUGUAACUAU UCCCAGGACAUGAUAAUAA UCUACACAGCUUCGGGAAG UCUCGCAACAAACUAUUUG GAAUCACUUGCACUCCGGA UGAAUCUAAAUUAU CAGUC GAAUCCUCCUGAUAACAUC AGAGGUAUGGCUGUAACUA GUCCCAGGACAUGAUAAUA GAUAACAUCAAGGAUACAA ACAAACUAUUUGUCGCAGG AAGGAUACUUUCUAGCUUG UAUUAAAAUUUCAUGCCGG UAGCCAGCCUAGAGGUAUG UGGCUGCUGAACCAGUAGA AGAAUCACUUGCACUCCGG AUUAAAAUUUCAUGCCGGG UGCAGUCUACACAGCUUCG GAUCUAUAAUGUUCACUGU GCAGUCUACACAGCUUCGG UUAAAAUUUCAUGCCGGGC AACAAACUAUUUGUCGCAG AAUUUAUUGACAAUACGCU AAAAUUUCAUGCCGGGCGC GUGUAGUGACGCAUGCCCU Ο Ϊ2; Q σ ω 〇〇VO $ Bu in Os 00 oo Os oo 〇m in Bu ON 152219.doc 62- 201130494 Ρ &lt;; ρ ρ U ο P υ C &lt; ϋ &lt;- &lt; 3 υ ϋ 〇 &lt; mouth P υ ο &lt; υ &lt; υ 〇ID ο &lt; 口ρ υ &lt; U υ Ο υ υ ϋ Ρ υ &lt; ϋ υ ο &lt;&lt; υ ρ &lt; ϋ &lt; υ ϋ υ ο &lt; ο 〇υ mouth &lt;&lt; ο ο Ρ 〇〇ϋ ϋ υ ο ο D &lt; o ο ο &lt;ϋ口&lt; D 口〇Ο υ &lt; υ &lt;&lt;&lt;〇&lt;&lt; 6 ο &lt; c U ϋ υ &lt; υ ο υ ΓΟ U υ υ Ρ ρ ο ϋ ϋ ϋ ο &lt; (j Ο ο 口υ ϋ &lt; υ ο ϋ mouth ο ο 〇ο Ο mouth &lt; 1D &lt;&lt;&lt;&lt; ρ &lt; ρ υ ϋ D D &lt; υ υ ο ϋ ϋ υ ο υ mouth &lt; υ Ρ υ ϋ ρ &lt; mouth &lt; υ υ ο &lt;&lt; ο &lt;&lt; ο υ &lt; υ &lt; ο Ρ ο ϋ &lt; Ο Ρ &lt; ο &lt; ρ 口 &lt; ο 口: D &lt; Ο ο ο &lt; ο &lt; ο υ υ iD &lt; υ υ &lt;&lt; υ ο ο υ &lt; ο &lt; υ ϋ ϋ ο ο υ ο υ υ &lt; υ υ mouth ο 2; Q α ω C/D CN (Ν inch &lt;Ν(Ν 00 CN ο m (Ν m ν〇m 00 m ο 142 144 〇 〇 υ υ υ &lt; ϋ &lt; Ο ϋ Ο ϋ &lt; CJ ο ο ϋ U u ο ο &lt; Ο υ ο ο υ &lt; D υ \D &lt; ϋ υ ϋ &lt;&lt; υ υ Ο &lt; υ &lt; υ &lt;&lt; g &lt;&lt;c υ υ &lt; ο &lt;口ο口&lt;&lt; ο &lt; &&lt; ϋ υ &lt; υ d &lt; ο ϋ ο υ &lt;! &lt; ρ &lt; Ρ ϋ ο υ &lt; υ υ ο &lt;〇&lt; 5 &lt; 5 ID D ρ &lt; ρ &lt ; ϋ υ ρ &lt; Ο ο ο υ 5 ο &lt; U &lt; υ υ &lt; ο 〇υ ο &lt; \5 &lt; 5 U υ υ υ ϋ υ υ Ρ &lt; υ ID ο U ϋ ο υ υ ο Ρ &lt;&lt;&lt;&lt; υ υ 〇 &lt; ϋ iD υ mouth ρ ο ο υ υ &lt; υ υ υ υ υ &lt; 1*JL· U ρ υ ϋ ϋ &lt; υ &lt; υ &lt; ο &lt; ϋ &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; ο &lt; υ ϋ ο ο υ ο &lt; o υ &lt; ϋ ρ υ ο ρ υ SlfJ^ &lt; Ρ ϋ ο u &lt;&lt;&lt; ο &lt;*&quot;1%&lt; Ρ ο υ ο &lt;&lt; ϋ υ Ρ 5 ϋ &lt;&lt; υ &lt; ϋ o &lt; ο &lt; υ ο Ζ Q Ο ω m yn (Ν Ν (Ν as CN mm ^Τ) m 137 139 152219.doc •63 201130494

田善is μ o :Standard deviation [%] 00 卜v〇m &lt;N m ΓΛ CN r-&gt; CO co &lt;N r*i •Ό C cc *〇c T3 c Tt o ON 00 00 00 00 v 〇trj *d •dc T3 C *dc CO Average remaining mRNA 丨%1 inch - ΙΛ PO vs VO »n On vs. m V) *〇c *〇c -Ό 6 Ό C •Ό C v-&gt; 〇\ m CM m 00 S o (N VO 妄»nc«-&gt; •dc *T3 c *6 c T3 dt * li 矣1 in *m _ spider S? 雔一一- (N — — one — (N CN CN (N - (N - (N - 卜 - d - &lt; N &lt; s (N (Μ (N &lt;N o «Λ v-&gt; CN — (N Ό C m mean residual mRNA [%l 〇 σΝ On Ov co Os ON o 二o 00 00 00 &quot;5J· »n inch*dd oo \〇«〇OO OO VO ζΐ ON ON T3 C anti-sense stock sequence (5'-3·) 1 ! UCGUUUUGAAcAGUGAAcAdTsdT 1 Η -Ό &lt; Ο Ο D α &lt; υ α DDDD Ο U g H T3 &lt; a D a &lt; O 〇DDD cS uo H 〇&lt; u 0 D a &lt; 1 a DD au *T3 u SP a ί u S 2 a 5 3 sy 3 | UCGUUUUGAAcAGUGAAcAdTsdT | H -o &lt; 1 a &lt; (ja DDDD augn &lt; 1 D aa DDD aya HI 〇&lt; oa D 〇&lt; oa 3 DDD aug H 〇U S da us 2 UC UC UC UC UC UC i DDD a H ? Ό o 5 ID a 6 CJ s 2 5 aay D | UUCGUUUUGAAcAGUGAACdTsdT | I CUUCGUUUUGAAcAGUGAAdTsdT I | GAAAGuAUCCUUCGuAUGAdTsdT I | CUuAUuAUcAUGUCCUGGGdTsdT | S 〇a D uuda D y D 5 D 2 2 CJ | GCuAGUCUUCGUUUUGAACdTsdT | H 1 T3 a DDDD 〇〇DDU a &lt; a 〇ia 3 DDD 〇UDDU 3 a &lt; δ a ? su S 5 δ 2 52 y 5 5 y OS 5 υ a | GCuAGUCUUCGUUUUGAACdTsdT | Η •ο 1 ο DDDD Ο υ DDU Ο &lt; υ α H *s ί a 3 DDD au DD a &lt; uau S 2 δ 2 3 ey 2 5 y D 〇ί 2 ua | GCuAGUCUUCGUUUUGAACdTsdT | •Ό ia DDDD au DDU 3 auo Η •σ i ο 3 DDD au DDU 3 a &lt; δ 〇s OS 2 2 2 3 S y 5 δ y O 2 ua | UGGCuAUCUUuAuAcAuACdTsdT I | CCGAUUUCCUUGGUcAAUGdTsdT | | UCCUGCGAcAAAuAGUUUGdTsdT ! H 〇3 ga &lt; 3 I 〇&lt; ouo DU ua | UGUUCUcAcAGGAGAGAGUdTsdT | SEQ ID NO &lt;Ν m 00 Sss $ o (N 00 § s 00 00 § s § ο S CN Tj- S VO 00 so &lt;N (N ?: rr (N (N oo &lt; N CN (N CN) stock sequence (5'- 3') uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT | ! uGuucAcuGuucAAAAcGAdTsdT | ί uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT | H 1 &lt; 〇1 o 3 o 3 3 a P s OH a 1 ga 3 i 〇H Write a 1 o 3 a OQ PS o H au 3 au &lt; 3 a P &quot;S s O Eg &lt; 〇u I a 3 &lt; 3 ps so | UfGUfUfCfACfUfGUfUfCfAAAACfGAdTsdT | | UfGUfUfCfACfUfGUfUfCfAAAACfGAdTsdT | | UfOUfUfCfACfUfGUfUfCfAAAACfGAdTsdT | H •Ό u 1 D 2 5 y 5 D s DH δ uy 2 D e 2 uy 2 s D GuucAcuGuucAAAAcGAAdTsdT | uucAcuGuucAAAAcGAAGdTsdT | ucAuAcGAAGGAuAcuuucdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | H • D &quot; D a 3 &lt; a 3 &lt; ao &lt; § P sso | GuucAAAAcGAAGAcuAGcdTsdT | | GuucAAAAcGAAGAcuAGcdTsdT | | GuucAAAAcGAAGAcuAGcdTsdT | | GuucAAAAcGAAGAcuAGcdTsdT | S5 Ό a &lt; 3 a 0 1 1 Η 1 -Ό Ο &lt; 1 α ί ο ί ο County s ο H ? Ό a &lt; 3 aa 1 β 2 Oj H 〇a &lt; 3 &lt; aas ο I GU fUfCfAAAACfGAAGACnjfAGCfdTsdT | Shu GUfUfCfAAAACfGAAGACfUfAGCfdTsdT | | GUfUfCfAAAACfGAAGACnjfAGCfdTsdT | I GUfUfCfAAAACfGAAGACfUfAGCfdTsdT | | GuAuGuAuAAAGAuAGccAdTsdT | | cAuuGAccAAGGAAAucGGdTsdT I cAAAcuAuuuGucGcAGGAdTsdT | E- • Ό square &lt; 〇o &lt; o 0 3 as &lt; 3 1 τ s O | AcucucuccuGuGAGAAcAdTsdT | ou Q c /) S 5 V) t; ON «〇3 sss Γ-» P JO ON m 00 00 00 s 5; σ\ 1 »〇5 &lt;N 〇s ίΝ ΓΛ »〇布ON &lt;N (N -64- 152219. Doc 201130494

® ί^) s &lt; Si μ&lt; ·5 «Λ Ο standard deviation 1%] σ\ 〇 00 o rf 00 VO TD c T3 C dc CN VO 00 u-&gt; VO v〇v〇〇\ • ό co vs. Os V~J (N *r&gt; average residual mRNA 丨%1 (S m fN in \〇P; VO CO Ό CO VO ON CM 卜 S • Ό C * T3 C -do 卜 amg § !n沄o 〇fM m •Ό C &lt;N (N s 〇\ (N 汔卜〇 \ oo ΒΡ铽5 wz ¢1 5 ί H standard deviation [%1 inch m inch m VO m fO T}· &lt;N Pair (N CM - 卜 - (N in CN 00 00 (N ΡΊ 卜 &lt; N « CN 〇 00 ΓΊ 1 inch v 〇 &lt; N mean residual mRNA [%] s 0's m 沄 * Ti ; q r-&gt; m OS m &lt;N (N &lt;N 〇\ CO r-&gt; m 〇\ CM 〇\ Oi σ\ VO (N m CM g: ΓΛ r- o CM m Ά antisense stock sequence (5·-3· 1 UfGUUCUCfACfAGGAGAGAGUfdTsdT H ? SD 〇&lt;〇&lt; a &lt; oauu port u DSD | uGUUCUcAcAGGAGAGAGudTsdT H a &lt; a &lt; a &lt; oa &lt; UDD a S 1 UfGUOJCUCfACfAGGAGAGAGUfdTsdT H ? S 〇&lt; a &lt; a &lt ; aa S uu DU δ D s D | UGUUCUcAcAGGAGAGAGudTsdT H a &lt; c &lt; a &lt; aa &lt; u D a SH β Έ, D a &lt; a &lt; a &lt; oauu DUDD sa H ? S 〇 &lt; o &lt; a &lt; oauy 2 y 2 D sa HD a &lt; a &lt; o &lt; aa 2S CJ u D CJ DD s DH sa &lt; a &lt; a &lt; aa S u S ΰ δ y 2 D sa 1 AAAGCGuAUUGUcAAuAAAdTsdT | AGUUUGUUGCGAGAGGAAGdTsdT | ACUuAuAAuAAAuAUGGUCdTsdT : 1 AGGCCGAUUUCCUUGGUcAdTsdT | H ? T3 &lt; UD aad DU u DD 3 &lt; auuaa &lt; H *O 〇D aa 3 D u CJ DDD &lt; auuaa &lt; H 〇y D a S 5 2 yy 2 δ &lt; syuoo &lt; | AGGCCGAUUUCCUUGGUcAdTsdT | H T3 Ό &lt; ao DDU u DD 3 &lt; auuoa &lt; Aa D u CJ DDD &lt; auuaa &lt; H ? XJ y D 〇 2 5 a ϋ y 5 5 &lt; sy υ oa &lt; AGGCCGAUUUCCUUGGUcAdTsdT | H *O &lt; υ 〇〇 DD CJ UDD 3 &lt; auuaa &lt; H 2 aa 3 D 〇〇DDD &lt; au CJ ao &lt; H *σ y D a 2 δ 3 yy 5 δ D &lt; syuaa &lt; uAGCuAGUCUUCGUUUUGAdTsdT | CUUCGuAUGAUGAAGAUUCdTsdT | *s DP aa D &lt; 〇D &lt; 3 aud 3 *s 3 D &lt; aa D &lt; a D &lt; 3 au D 3 a H a &lt; 〇SD &lt; s DD sy 2 2 u CUU C GuAUGAUGAAGAUUCdTsdT | H •g DD 〇o D &lt; 〇D &lt; a CJ D 3 H 〇3 P aa D &lt;〇&lt; c! u D 3 Q. H β S ΰ cS D &lt; ae D &lt; s 25 D s ΰ δ 2 u CUUCGuAUGAUGAAGAUUCdTsdT | H *〇口 aa D &lt; ϋ D &lt; 3 ou D o H •g 3 D &lt; 〇o D &lt; 〇D &lt; au D 3 H Ze ya D &lt; a D &lt; s DDS y 2 2 u SEQ ID NO Tt CM Cold CN 00 CN CN O &lt;N (N ΓΟ ΓΟ is SO m (N 00 o (N Tt VO (N o CM fN (N CN Ό (N 00 fM § &lt;N s (NS &lt;N cs $ &lt;N o (N JN (N Ν 00 (N o 00 (N s (N (N &lt;N i§ &lt;N g ΓΜ &lt;NS fM v〇Cs (N &lt; NO (N shares sense sequence (5'-3 '&gt; | AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT I AcucucuccuGuGAGAAcAdTsdT H 〇1 a &lt; o 3 o 3 〇og 3 special o H &quot;Ό 1 a &lt; a 3 a 3 O 3 O 3 o I ACfUfCfUfCfUfCfCfUfGUfGAGAACfAdTsdT 1 ACfUfCfUfCfUfCfCfUfGUfGAGAACfAdTsdT 1 uuuAuuGAcAAuAcGcuuudTsdT | cuuccucucGcAAcAAA cudTsdT | GAccAuAuuuAuuAuAAGudTsdT 1 uGAccAAGGAAAucGGccudTsdT 1 uGAccAAGGAAAucGGccudTsdT | uGAccAAGGAAAucGGccudTsdT ; 1 uGAccAAGGAAAucGGccudTsdT H *OO 〇o 3 ί s | H 0·&gt; S 〇·〇〇a D ί aa | P Έ 2 OH 〇oaa 3 ί ao PS o H 2 Ό § a 0 3 1 aa &lt; u P a &gt; 2 O UfGACfCfAAGGAAAUfCfGGCfCfUfdTsdT | UfGACfCfAAGGAAAUfCfGGCfCfUfdTsdT | UfGACfCfAAGGAAAUfCfGGCfCRJfdTsdT | UfGACfCfAAGGAAAUfCfGGCfCfUfdTsdT | ucAAAAcGAAGAcuAGcuAdTsdT | GAAucuucAucAuAcGAAGdTsdT | GAAucuucAucAuAcGAAGdTsdT | GAAucuucAucAuAcGAAGdTsdT | GAAucuucAucAuAcGAAGdTsdT | H si 〇3 &lt; 3 &lt; 3 3 3 Z * N o H β ? S a S &lt; 3 3 3 o H sa &lt; &lt; 1 0 1 1 o H sa &lt; 3 &lt; 3 &lt;? 3 3 i S GAAUfCfUaJfCfAUfCfAUfACfGAAGdTsdT | GAAUfCfUfUfCfAUfCfAUfACfGAAGdTsdT | GAAUfCfURJfCfAUfCfAUfACfOAAGdTsdT | GAAUfCflJfUfCfAUfCfAUfACfGAAGdTsdT fo σζ Zizania a fN CN « CM CM CM OS (N CN δ ΡΛ (N tn m CM On ΓΟ CN \Ti ri Ν Ό Γ 4 in Ό tN (S Os U-ϊ (N ss &lt;N !〇cs Os o ΓΜ rn 5 fN 卜 ON fS 00 fN m 00 &lt;N 00 CN oo &lt;N &lt;N a »n On (N a as 〇\ (N § 152219.doc •65- 201130494 BS I •δ- ^ S &lt; =i ^ '5 ^ S &gt;Λ o *w a «t- 5? 雎6 C Τ3 ΓΛ 00 卜 〇 Ό Ό C *dc •acdd *dc *〇c ·〇c DC 〇c -Ό C *dc *dc *〇c T3 c T3 c ·〇c *OC *dc *dc •ac *〇c *〇c ·〇c *dd *〇c Ό C d σ c *OC Average remaining mRNA |%1 &quot;0 •dc K VO m (NP 〇C *6 c •dc ·〇c seven cdc T3 c 〇c •Ό C *dc •dc •acocac σ c •dc Ό C dddddc T3 C ·〇c 〇c Ό C T3 d Ό C •Ό C 〇coc BP绂S Έ Z «1 S»5 H μ * lo in standard deviation [%] «Ν一&lt;N &lt;N &lt;N &lt;N 一卜m (N fN CN (N *n one ( N (N r*-&gt; CN vs. CM v〇&lt;N 00 r-&gt; (N (N m-inch average residual mRNA |%1 y-&gt; (NV) (NP 〇*〇P; Os o 〇 5 00 •r&gt; «〇5 § CO •T) &lt;N VO m so PP jn Antisense stock sequence (5'-3'&gt; | AAcAUuAuAGAUCuAUCCCdTsdT I 1 UuAUUCCUGCGAcAAAuAGdTsdT | | AGUcAuAUCUUcAAAuAGAd TsdT IH 〇 &lt; 3 1 δ D &lt;&lt; 〇 &lt; H σ &lt; ϋ D 1 y 2 ay D y D ϋ &lt; | AGUcAuAUCUUcAAAuAGAdTsdT IH &lt; a &lt; 3 1 3 u D &lt; 3 &lt; D a &lt; H 〇 &lt; a 1 y 2 ay 3 y DU &lt; | AGUcAuAUCUUcAAAuAGAdTsdT | H 〇&lt; 3 δ &lt; 3 &lt; D 〇&lt; H ·〇&lt; 〇D 1 y 2 δ y D y D a &lt;!! 1 UGCGAcAAAuAGUUUGUUGdTsdT | | UCCUUCGuAUGAUGAAGAUdTsdT I 1 AAAuAGUUUGUUGCGAGAGdTsdT II UUCGuAUGAUGAAGAUUcAdTsdT I AAGCGAUCUGGAAGGUCUGdTsdT II UGCGAGAGGAAGCGAUCUGdTsdT I GUuAcAGCcAuACCUCuAGdTsdT | I AAGCGuAUUGUcAAuAAAUdTsdT | | AuAAAGuAAAGCGuAUUGUdTsdT I | GCuAGAAAGuAUCCUUCGUdTsdT | | UGcACUGGGAGAcAAUUCCdTsdT II CCCGAAGCUGUGuAGACUGdTsdT I | AAAGuAUCCUUCGuAUGAUdTsdT | | UCGuAUGAUGAAGAUUcAAdTsdT | | CGuAUGAUGAAGAUUcAAAdTsdT | I GUUGCGAGAGGAAGCGAUCdTsdT I | AuAGUuAcAGCcAuACCUCdTsdT | | UuAUuAUcAUGUCCUGGGAdTsdT | I CUUCCCGAAGCUGUGuAGAdTsdT I | cAAAuAGUUUGUUGCGAGAdTsdT | | UCCGGAGUGcAAGUGAUUCdTsdT II GACUGAuAAUUuAGAUUcAdTsdT I i GAUGUuAUcAGGAGGAUUCdTsdT | | uAGUuAcAGCcAuACCUCUdTsdT I | uAUuAUcAUGUCCUGGGACdTsdT I | UUGuAUCCUUGAUGUuAUCdTsdT | I CCUGCGAcAAAuAGUUUGUdTsdT I | cAAGCuAGAAAGuAUCCUUdTsdT | | CCGGcAUGAAAUUUuAAuAdTsdT | SEQ ID NO v〇〇〇o fO (NV〇PO 00 CO 〇&lt;N ΓΟ m VO (N 00 (N 〇m (N CO VO r **&gt; 00 m 〇CO 5 m NO 00 o (N r-&gt; \〇sn 00 \no VO m &lt;N v〇sm VO VO 00 VO 〇&lt;N m VO CO 〇〇o 〇〇( N 00 shares sense sequence (5'-3 ') GGGAuAGAucuAuAAuGuudTsdT | | cuAuuuGucGcAGGAAuAAdTsdT | | ucuAuuuGAAGAuAuGAcudTsdT | | ucuAuuuGAAGAuAuGAcudTsdT | | ucuAuuuGAAGAuAuGAcudTsdT | t- • Ό · 〇o &lt; 〇s &lt; s &lt; aa circle &lt; the SPS 〇H * 〇o &lt; 〇3 &lt; &lt; AA around &lt; 3 S o H 1 1 &lt; 3 &lt; o 0 1 &lt; S ps S o | UfCfUfAUfUfUfOAAGAUfAUfGACfUfdTsdT 1 | UfCfUfAUfUfUiOAAGAUfAUfGACfUfdTsdT] 1 UfCfUfAUfUfUfGAAGAUfAUfOACfUfdTsdT | | cAAcAAAcuAuuuGucGcAdTsdT | | AucuucAucAuAcGAAGGAdTsdT | cucucGcAAcAAAcuAuuudTsdT uGAAucuucAucAuAcGAAdTsdT | cAGAccuuccAGAucGcuudTsdT I cAGAucGcuuccucucGcAdTsdT I cuAGAGGuAuGGcuGuAAcdTsdT | AuuuAuuGAcAAuAcGcuudTsdT | AcAAuAcGcuuuAcuuuAudTsdT | | AcGAAGGAuAcuuucuAGcdTsdT | | GGAAuuGucucccAGuGcAdTsdT | cAGucuAcAcAGcuucGGGdTsdT 1 | AucAuAcGAAGGAuAcuuudTsdT | | uuGAAucuucAucAuAcGAdTsdT | uuuGAAucuucAucAuAcGdTsdT | GAucGcuuccucucGcAAcdTsdT | GAGGuAuGGcuGuAAcuAudTsdT] ucccAGGAcAuGAuAAuAAdTsdT | | ucuAcAcAGcuucGGGAAGdTsdT | ucucGcAAcAAAcuAuuuGdTsdT | GAAucAcuuGcAcuccGGAdTsdT 1 | uGAAucuAAAuuAucAGucdTsdT] GAAuccuccuGAuAAcAucdTsdT 1 AGAGGuAuGGcuGuAAcuAdTsdT | | GucccAGGAcAuGAuAAuAdTsdT] | GAuAAcAucAAGGAuAcAAdTsdT [AcAAAcuAuuuGucGcAGGdTsdT | AAGGAuAcuuucuAGcuuGdTsdT uAuuAAAAuuucAuGccGGdTsdT | o az Sa ΡΛ s CO % 卜 PO Os m tN mr*&gt; (N m ό ΓΛ a &lt;N ΓΛ mm ro Pi 〇s ro 5 ro w-&gt;?; 5 m V*J u- &gt; m Os mm 3 r*&gt; VO mv〇r&quot;&gt; !S ΓΛ 〇s P m jn 卜 $ as 〇〇m -66- 152219.doc 201130494

Be! Every 1 p 2 zz -3⁄4 H «« O Standard deviation [%] *dc -d *dc *〇d •dc *dc 〇c T3 C -dc -dc T3 dc C T3 C T3 C ~6 c - Dc •dc 6 c *dc &quot;T3 d *〇cqcc σ c *dc •dc -〇cdc *DC &quot;d -dc ~6 c *〇c *dc •Ό C T3 C •ac Average Remaining mRNA [% ] qd 〇c Ό C c T3 c *6 d *de -oc *T3 c *6 c ·〇c •Ό C Ό c Ό C acdc •nc T5 c *〇d •DC adccccc C cc BF绂SW z $1 ^ 55 =1 H '5 1 o to standard deviation _ [%] VJ v〇 Bub 00 os r- Os (N Os vs. r- VO 00 is inch (N (N VO VO average residual mRNA 丨0Λ1 (N卜On (N 00 0〇(N 00 v〇00 00 00 ss z ON oo ON 00 00 ON 〇\ (N ssg On s OO On s 〇 〇 v〇&lt;N 沄fN (N CO CN (N (N Unit antisense sequence (5'-3 ') | cAuACCUCuAGGCUGGCuAdTsdT [UCuACUGGUUcAGcAGCcAdTsdT 1 CCGGAGUGcAAGUGAUUCUdTsdT | CCCGGcAUGAAAUUUuAAUdTsdT 1 CGAAGCUGUGuAGACUGcAdTsdT 1 AcAGUGAAcAUuAuAGAUCdTsdT 1 CCGAAGCUGUGuAGACUGCdTsdT 1 GCCCGGcAUGAAAUUUuAAdTsdT 1 CUGCGAcAAAuAGUUUGUUdTsdT 1 AGCG uAUUGUcAAuAAAUUdTsdT I GCGCCCGGcAUGAAAUUUUdTsdT | AGGGcAUGCGUcACuAcACdTsdT 1 GCGuAUUGUcAAuAAAUUUdTsdT 1 GCCGAUUUCCUUGGUcAAUdTsdT i | GAGGGcAUGCGUcACuAcAdTsdT | 1 uAuAAuAAAuAUGGUCCGGdTsdT | 1 CcAuACCUCuAGGCUGGCUdTsdT | | UGAGGGcAUGCGUcACuACdTsdT | 1 GGGAUUGAGGGcAUGCGUCdTsdT | 1 CCUUCGuAUGAUGAAGAUUdTsdT | [cAAAuAGAGGCCGAUUUCCdTsdT |! AGCGAUCUGGAAGGUCUGAdTsdT | cAGUcAGAAUcAGUcAuAUdTsdT | CUCuACCUCCGGAGUGcAAdTsdT | UCuACCUCCGGAGUGcAAGdTsdT | GGAUUGAGGGcAUGCGUcAdTsdT | GAAAGuAUCCUUCGuAuGAdTsdT | GAAAGUfAUCCUUCGUfAUfGAdTsdT | GAAAGUfAUfCfCaJfUfCfGUfAUfGAdTsdT | cCGAUUUCCUUGGUcAAuGdTsdT | CfCGAUUUCCUUGGUCfAAUfGdTsdT | E- * O ϋ 3 3 aa DU u DDD &lt; aya 〇s DSD aad DU CJ DDD &lt; 〇yu CfCfGAUaJfUfCfCfUaJfGGUfCfAAUfGdTsdT | CuuAuuAucAUGUCCUGGGdTsdT | CUfUfAUfUfAUfCfAUGUCCUGGGdTsdT | CuuAuuAucAUGUCCUGGGdTsdT | CfUfUfAUaJfAUfCfAUGUCCUGGGdTsdT | H 1 aoo DU o D a D &lt; 3 3 &lt; 3 3 〇H 1 S 〇aduu D o D ί y D 2 D 2 5 u SEQ ID NO 1 384 1 386 | 388 | 390 1 392 1 394 1 39 6 00 ON | 400 1 402 〇 | 406 | 408 io (N inch 00 inch 1420__ 1422__I ^24__ ! 426 I i 428 | 430 | 432 1 434 | VO 438 | 440 | 442 | 444 | 446 | Tj* 450 1 452 1 454 | 456 | 458 | 460 1 462 | sense shares sequence (5'-3 ') | uAGccAGccuAGAGGuAuGdTsdT | uGGcuGcuGAAccAGuAGAdTsdT 1 AGAAucAcuuGcAcuccGGdTsdT I AuuAAAAuuucAuGccGGGdTsdT | uGcAGucuAcAcAGcuucGdTsdT | GAucuAuAAuGuucAcuGudTsdT | GcAGucuAcAcAGcuucGGdTsdT 1 uuAAAAuuucAuGccGGGcdTsdT 1 AAcAAAcuAuuuGucGcAGdTsdT | AAuuuAuuGAcAAuAcGcudTsdT 1 AAAAuuucAuGccGGGcGcdTsdT | GuGuAGuGAcGcAuGcccudTsdT | AAAuuuAuuGAcAAuAcGcdTsdT Shu AuuGAccAAGGAAAucGGcdTsdT [uGuAGuGAcGcAuGcccucdTsdT 1 ccGGAccAuAuuuAuuAuAdTsdT | AGccAGccuAGAGGuAuGGdTsdT GuAGuGAcGcAuGcccucAdTsdT | 1 GAcGcAuGcccucAAucccdTsdT | AAucuucAucAuAcGAAGGdTsdT | GGAAAucGGccucuAuuuGdTsdT | ucAGAccuuccAGAucGcudTsdT AuAuGAcuGAuucuGAcuGdTsdT | uuGcAcuccGGAGGuAGAGdTsdT | cuuGcAcuccGGAGGuAGAdTsdT | uGAcGcAuGcccucAAuccdTsdT | ucAuAcGAAGGAuAcuuucdTsdT | ucAuAcGAAGGAuAcuuucdTsdT | ucAuAcGAAGGAuAcuuucdTsdT | CAuuGAccAAGGAAAucGGdTsdT | cAuuGAccAAGGAAAucGGdTsdT | cAuuGAccAAGGAAAucGGdTsdT | cAuuGAccAAGGAAAucGGdTsdT [cAuuGAccAAGGAAAucGGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | SEQ ID NO m 00 00 1 387 Shu 389 | 393 〇s | 397 | 399 o S 1 L4〇5_I U〇7_ 409 | inch r*» tj- *n inch 5 523__ 1425__I 1427__I 1429_1 5 L«5_1 1437__ 1439I 1443__I 1445___1 1447I | 449 | r*&gt; | 455 I 1457_I | 459 I 152219.doc

-67- 201130494 ϋε % 本 i 5 &lt; S 2 ^ DS yso 蜊 - 跻5? 雔一•Ό C &quot;Ό C 〇C Ό C ·〇C Τ3 C •σ ~6 c 〇*σ &quot;Ό C *σ c ~〇d -Ό C *dd •dc -ad Ό C t3 *dcd &quot;O c 七e •dc *6 c DC dc σ c average residual mRNA [%| *〇C 〇C Ό C xi c •ο C •ό c -q •Ό C •σ -〇c -σ c Ό C -oc 〇Ό ddd Ό •o *dd •ac Τ3 d ·〇C 七c Ό C •dc *T3 w $i 5 W Γ tl «35 -ii Η ·35 *1 ΙΛ 甽_ * S? 雎- madaa CM Average remaining mRNAi%! 〇〇〇\ ο ο OS Os On fN On &lt;N P&lt;J VO m (N ( N *a *dc V£&gt; •ο 呀 rr Art antisense stock sequence (5'-3·) I CflJfUfAUaJfAUfCfAUfGUfCfCfUfGGGdTsdT | I UfCCUGCGACfAAAUfAGUUUfGdTsdT 1 | DUfCCUGCGACfAAAUfAGUUUfGdTsdT 1 I uCCUGCGAcAAAuAGUUuGdTsdT 1 Η σ α D α &lt; 3 ί Ο υ ο D Ο CJ S 1 UfCCUfGCGACfAAAUfAGUUUfGdTsdT 1 Η Ό SDDD Ο D face U &lt; α υ 52 =) υ α | UCCUGCGAcAAAuAGUUuGdTsdT IH 2 S s DD 〇&lt; 3 1 auauu S | UfGGCUfAUCUUUfAUfACf AUfACdTsdT I E- ? SD ί U $ DDD 〇D iS DU a S a | uGGCuAUCUUuAuAcAuACdTsdT I [- I JO &lt; 3 &lt;&lt;&lt; 3 DUD &lt; 3 uao 巨 | UfGGCUfAUCUUUfAUfACfAUfACfdTsdT | E- ? 2 u DUDDDDUDDU a SDI uGGCuAUCUUuAuAcAuACdTsdT IH *s &lt;&lt;&lt; 5 DDUD &lt; U 〇aa 3 &lt; 3 &lt; U &lt; 3 &lt; D 5 D &lt; δ aa 6 H ? s &lt; 0 &lt;&lt; 1 DUD &lt; U aa SH s &lt; 3 &lt;&lt; i c3 D &lt; U ao S | UfGUUCUCfACfAGGAGAGAGUfdTsdT 1 H ? sa &lt; a &lt; o &lt; oouu D uo DSD Γ uGUUCUcAcAGGAGAGAGudTsdT | h- *σ a &lt; a &lt; o &lt; aa &lt; O &lt; UD oa giant | UfOURJCUCfACfAGGAGAGAGUfdTsdT | H Ξ D a &lt; a &lt; a &lt; oa ί ou DU 5 D s P | UGUUCUcAcAGGAGAGAGudTsdT | H •Ό 〇&lt; a &lt; a &lt; 0 a &lt; 1 DUD 3 a Giant SEQ ID NO 1 $ 〇Ρ inch 00 inch I &lt;N 00 00 oo 碁 vo 00 5 O s »ng V-) v〇00 O »r&gt; (N » n \〇00 sense strand sequence (S'-3'&gt; cccAGGAcAuGAuAAuAAGdTsdT | cAAAcuAuuuGucGcAGGAdTsdT | cAAAcuAuuuGucGcAGGAdTsdT | cAAAcuAuuuGucGc AGGAdTsdT cAAAcuAuuuGucGcAGGAdTsdT cAAAcuAuuuGucGcAGGAdTsdT cAAAcuAuuuGucGcAGGAdTsdT | cAAAcuAuuuGucGcAGGAdTsdT | | cAAAcuAuuuGucGcAGGAdTsdT | | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | 1 GuAuGuAuAAAGAuAGccAdTsdT | 1 GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT [GuAuGuAuAAAGAuAGccAdTsdT | | GuAuGuAuAAAGAuAGccAdTsdT I GuAuGuAuAAAGAuAGccAdTsdT I GuAuGuAuAAAGAuAGccAdTsdT I 1 GuAuGuAuAAAGAuAGccAdTsdT I 1 GuAuGuAuAAAGAuAGccAdTsdT | [AcucucuccuGuGAGAAcAdTsdT | | AcucucuccuGuGAGAAcAdTsdT AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT | o UQ \〇时v&gt; $ P inch jn vs ac 1 Os inch 5 sm Vi «η Os 卜

152219.doc -68 - 201130494

ε&lt;Equivalent IC20 for dose response in HCT-116 cells [nMl 0.002718 0.002716 0.000365 0.001964 dd ά 0.002450 0.001577 0.000680 0.002361 ά Τ3 ά 0.000679 0.000389 Τ3 ά 0.002893 0.004496 0.017737 0.006392 0.006114 0.080584 0.020273 0.010403 0.005371 0.003400 0.022881 0.033305 0.009591 Average IC80 ΓηΜΙ 0.179733 0.217502 0.064567 0.170232 ά -dd 0.199288 0.178343 0.122262 0.127355 ά ά 0.116178 0.142359 ή 0.618554 1.447999 1.284626 1.852002 0.456882 137.634263 4.243508 1.097069 7.703471 0.240469 5.408701 4.187072 1.846414 Average IC50 fnMl 0.019705 0.023803 0.005502 0.019388 ά C 0.021061 0.016416 0.009866 0.012408 ά ά 0.008763 0.007031 d 0.039988 0.060112 0.096586 0.046597 0.048791 0.375545 0.149802 0.068681 0.039770 0.016327 0.226873 0.167762 0.097979 SEQ ID NO pair 149/150 151/152 153/154 155/156 157/158 159/160 161/162 163/164 165/166 167/168 169/170 171/ 172 173/174 175/176 177/178 179/180 181/182 183/184 185/186 187/188 189/190 213/214 215/216 217/218 219 /220 221/222 225/226 239/240 152219.doc -69- 201130494

The average IC20 for dose response activity in HCT-116 cells [nMl 0.072635 0.009603 0.007672 0.005680 0.051137 0.012149 0.006169 0.000001 0.000006 1 0.000049 0.000021 1 0.000027 0.000018 0.000054 0.000059 0.000286 1 1 0.001548 1 0.000803 0.000117 Average IC80 ΓηΜ] #DIV/0! 2.397850 0.651588 0.896165 8.194878 0.345758 0.265070 0.394600 0.096035 0.220231 0.458293 0.367181 0.594412 0.176818 0.732077 0.711772 4.264770 0.232121 16.697845 0.965829 113.757404 1.442494 1.079470 0.587074 Average IC50 fnM] 0.505119 0.049475 0.047339 0.045178 0.224969 0.042519 0.035639 0.003620 0.001034 0.003253 0.010785 0.010853 0.012595 0.005607 0.012207 0.008412 0.062875 0.006647 0.084889 0.006412 0.481099 0.021174 0.039219 0.023727 SEQ ID NO: 241/242 243/244 253/254 255/256 279/280 293/294 295/296 435/436 461/462 463/464 465/466 467/468 469/470 471/472 473/474 475 /476 477/478 479/480 485/486 487/488 493/494 495/496 499/500 501/502 152219.doc •70- 201130494 Human PBMC assay TNF-a 〇o 〇oooo 〇 o 〇ooooooo (N oo ο Ο Ο Ο ο Ο IFN-a oo 〇CN oooo 〇oooooooooo ο ο ο ο ο Qualitative human ARDS (sputum) Έ Ci KT) o r-; O) T3 C T3 C - Dc T3 c -DC -dc T3 C TD C T3 C (N 26.1 22.8 rH (N 19.5 00 o ΘΟ 00 TD c &gt;48 Τ3 C 13.7 21.6 17.4 10.6 (Ν cn cup g C! Oral wear | nd Ό C TD d TD d TD C &quot;D d -dd TD C TD C 00 inch oo oo -Ό C &gt;48 Τ3 C &gt;48 &gt;48 &gt;48 &gt;48 &gt;48 Stability Cynomolgus BALf (allergic Original attack) Έ Ci — -qc T3 C T3 ή T3 d -Ό d -T3 C T3 d T3 dqd -〇c TD c T3 C -dd -oc xi c TD C -T3 C qd T3 d &quot;dd TD d TD C &gt;48 -〇d &gt;48 &gt;48 &gt;48 &gt;48 31.9 ΈCJ 〇d TD C -T3 d T3 d T3 c C c -dd -qc 〇c -TD d T3 C c TD C T3 C T3 d T3 C TD c TD c Ό CX) d T3 C &gt;48 •ο ή &gt;48 &gt;48 &gt;48 &gt;48 &gt;48 Stability Human Serum ε εί 2.60 〇c -dc T3 d I 2.50 7.80 9.30 15.70 T3 d 6.90 j 4.70 _LMJ -T3 d I 3.20 | T3 C dc -nc Ό d ·〇c TD C T3 C &gt;48 &gt;48 &gt;48 16.2 yA 20.3 24.6 14.3 cup Έ CJ — 19.90 TD d T3 d -dd 7 l &gt;24 7 T3 c 1__&gt;241 18.60 &gt;24 qc &gt;24 | d T3 c T3 C qc T3 C TD d - DC &gt;48 25.6 &gt;48 &gt;48 &gt;48 &gt;48 &gt;48 Stability cynomolgus plasma antisense ΈCJ 4.30 00 Os 10.6 | 4.00 3.10 4.50 2.70 -qc 10.50 1 3.30 | o *dc | 5.30 (N Os 16.6 17.8 00 (N 00 &lt;N rn 寸 rn m rn 12.2 &gt; € Έ CJ 4.30 11.2 12.7 cn | 3.80 5.90 13.20 3.00 *dd 12.50 3.00 i 7.60 〇c | 12.40 | 20.7 12.5 VO 寸00 CN 卜(N ν-ϊ 14.9 00 ν〇11.3 18.9 17.6 SEQ ID NO pair 149/150 163/164 165/166 173/174 1 179/180 181/182 183/184 185/186 187/188 213/214 215/216 217/218 219/220 | 221/222 | 239/240 243/244 253/254 255/256 279/280 293/294 295/296 435/436 461/462 463/464 471/472 473/474 475/476 479/480 487/488 152219.doc

• 71 201130494 Unit antisense sequence (5'-3 ') UCAGUCAUAUCCUCGAACA ACUGCGGUUGUACAGUGAA UCUUUUGUCAACGAAGAGA GAGGGUAGACAUUUUACUA UGACGCAAGAGUCUUCUGA UCAGGUAUAAAGUAAAGCG UGUAUAUUAUCAGUCUGGU UCGAACACAGGCUGUCUUU AUUUUACUAUCCUUCACAG AAAGCGUGUUGUCAAUAAA CUCGGGUAUUCUGUUAUGG AUAAACAUCAUUUCCUUGA UGCGGUUGUACAGUGAAGU UAUUCCGUAUUACUGCGGU AAGAAUAUGAGAUCACUUU UUGAAAGCAUCAUCUUCCU UUUGAGGCGGCUUUCUXJUG GUGUUGUCAAUAAACAUCA AAGUUAGUGAGAGUGAACA GAGGCGGCUUUCUUUGUCC UUCCGUAUUACUGCGGUUG GGUUUGAGGCGGCUUUCUU UUCUGAAAGAAUAUGAGAU GCCUCGGGUAUUCUGUUAU CAUAUCCUCGAACACAGGC UAAAGCGUGUUGUCAAUAA GAUGUAAGUUAGUGAGAGU UACUCUAUAAAUCAUGCAG SEQ ID NO 520 522 yn 526 00 &lt;N 530 CN 寸m κτ) 〇〇m KTi o 542 544 546 oo 550 &lt;N yr) 554 556 OO yr) yr) 〇VO cs 564 566 00 o 572 Sense stock sequence (5'-3&quot;&gt UGUUCGAGGAUAUGACUGA UUCACUGUACAACCGCAGU UCUCUUCGUUGACAAAAGA UAGUAAAAUGUCUACCCUC UCAGAAGACUCUUGCGUCA CGCUUUACUUUAUACCUGA ACCAGACUGAUAAUAUACA AAAGACAGCCUGUGUUCGA CUGUGAAGGAUAGUAAAAU UUUAUUGACAACACGCUUU CCAUAACAGAAUAC CCGAG UCAAGGAAAUGAUGUUUAU ACUUCACUGUACAACCGCA | ACCGCAGUAAUACGGAAUA AAAGUGAUCUCAUAUUCUU AGGAAGAUGAUGCUUUCAA CAAAGAAAGCCGCCUCAAA UGAUGUUUAUUGACAACAC UGUUCACUCUCACUAACUU GGACAAAGAAAGCCGCCUC CAACCGCAGUAAUACGGAA AAGAAAGCCGCCUCAAACC AUCUCAUAUUCUUUCAGAA AUAACAGAAUACCCGAGGC GCCUGUGUUCGAGGAUAUG UUAUUGACAACACGCUUUA ACUCUCACUAACUUACAUC CUGCAUGAUUUAUAGAGUA SEQ ID NO 519 (N m (N κη in (N 527 529 533 in m 5 539 543 547 549 553 555 557 ON m vo to 567 569 卜 152219.doc -72- 201130494 o iD 〇&lt;&lt; lt ο &lt;&lt; ο &lt; ϋ υ Ο Ρ &lt; υ &lt; υ &lt; Ο &lt;&lt; ϋ ρ υ &lt; ao &lt &lt;&lt;3 Ο υ ο υ &lt;&lt; υ 〇&lt; Ο ϋ &lt; υ &lt; ο υ &lt; ϋ υ PU u PU Ο &lt; ο υ Ρ υ &lt;口&lt; Ο υ ρ ϋ ρ Ρ &lt; Ο &lt; ο &lt;&lt;d&lt; ο ϋ &lt;! \ho &lt; a ϋ Ο υ &lt; υ ϋ υ υ υ ρ ϋ ϋ &lt; ο HD ϋ 〇P up υ ο &lt;&lt;&lt;&lt; υ Ρ &lt;&lt;&lt;&lt; ρ &lt;&lt;&lt; υ D &lt; Ρ uo &lt; U υ ϋ ϋ &Lt; υ υ υ ο ρ 〇υ mouth D &lt; υ υ ο &lt; υ ο υ 'ρ &lt; u &lt; ρ &lt; Ρ Ρ ο C &lt; ο D a υ 'ρ ο ρ ϋ ο υ Ρ ^ cW o υ 〇υ &lt; ο &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;d Ο ο ο υ &lt;&lt;&lt;&lt;&lt; ο o ο &lt;&lt; υ D &lt; Ρ υ ρ ο ο &lt;&lt; 口 a ρ ϋ &lt; υ υ &lt;&lt;&lt; D &lt;&lt;&lt; U U 〇υ &lt; Ρ ο &lt;&lt;口&lt; υ口υ Ρ U a ο Ρ ο &lt; 口ρ ο υ 口 &lt; u &lt;&lt; U &lt; ο υ ο ϋ Ο &lt; ο 口ρ Ρ Ρ &lt; ο &lt;&lt; 〇oup &lt;&lt;&lt;&lt;&lt; υ &lt; υ ο 口ο υ &lt; ο υ ο Ο &lt;&lt;; 5 ο Ρ &lt;1 ο Ο u &lt; 〇U υ &lt;&lt;&lt; ϋ 5 &lt; ο &lt;&lt; υ υ ϋ &lt;&lt; ο tD 5 &lt; Ο uu &lt;&lt; 〇U ρ &lt; ϋ &lt; υ &lt; υ ρ ο 口 &lt; ο υ ϋ &lt; ο ρ υ P 〇υ &lt; 'Ρ &lt ϋ口ο υ υ &lt;&lt; D ο U ϋ ρ ο &lt; ϋ 口ϋ D &lt; ο 5 \b &lt;&lt; ο ο &lt;&lt; ο 口ο ο Ρ ϋ Ρ &lt; D ο &lt; ο υ &lt; υ &lt; ο ID ϋ υ u &lt; 〇ρ υ Ρ ο &lt;&lt;&lt;&lt; Ο ϋ Ρ ο υ ϋ υ &lt;&lt;&lt; ο &lt; 〇υ ο υ ϋ ο ο ρ ο &lt;&lt;&lt; lt ο &lt; υ ο υ υ υ Ο ο ο &lt; o υ &lt;口ο;3 υ C υ &lt;&lt;&lt;&lt; ρ &lt; υ ο ο C Ρ &lt; ο &lt; SEQ ID NO yn 00 m ο οο &lt;η CN 00 ^Ti 00 00 οο (Ν as ^Τ) 寸Ον 家 iri i〇ο § SS ν〇S g \〇ο ν 〇 (Ν νο ο ν 〇 〇 Ν Ν Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο ϋ Ο Ο ϋ ϋ Ο ϋ ϋ ϋ ϋ ϋ ϋ ϋ ϋ ϋ ϋ Ο Ο Ο Ο Ο Ο Ο Ο Ο Ο ; ρ &lt; (J tD &lt;&lt; υ &lt;&lt; Ο &lt;: υ &lt; υ &lt;; υ ρ &lt; ϋ υ Ρ ο υ υ ο &lt;&lt; o 〇Ο υ ϋ Ο U ΪΛ D o UDU &lt; ο &lt; υ &lt;&lt; υ &lt; Ρ &lt;&lt;&lt; υ υ &lt; ο υ ϋ \D &lt;&lt; CJ ο &lt; υ &lt; CJ υ &lt;&lt; υ &lt; υ ο a 口o &lt;(J;=) υ υ 〇wk &lt;&lt;&lt; U 〇&lt;&lt; υ &lt;; υ ο ϋ &lt; ο υ ο Ρ υ &lt; C ο &lt;&lt; 〇o 口 U Ο &lt;&lt; Ρ υ Ο Ρ ο &lt; ο υ &lt;&lt; Ρ &lt; υ o υ Ο υ ρ &lt; 〇〇 &lt; U ϋ ο ρ Ρ υ &lt; 口υ Ρ Ο ο &lt; υ ρ ρ &lt; υ &lt;&lt; ρ &lt; ρ υ υ «iuo &lt; ϋ \D Ρ ο 口ο υ &lt; υ ο &lt; ο &lt; υ C ID \D &lt;&lt; υ &lt;&lt; υ &lt; P &lt;&lt;&lt; ϋ ϋ ο υ υ ο &lt; υ &lt;&lt; υ &lt; Ρ 〇υ &lt; 〇υ ϋ &lt ; Ρ Ρ &lt; ο &lt; Ο &lt; 口ο υ υ &lt; ρ &lt; υ &lt;&lt;; Ο &lt;&lt; u υ &lt;&lt; ο &lt; 3 &lt; ο &lt; υ υ Ο ρ &lt; ϋ &lt; υ ϋ ο \D &lt; u &lt; 〇υ &lt; ο υ &lt; D &lt; Ρ &lt; ID υ &lt; υ ο ο 5 υ mouth &lt;&lt; (J &lt; o &lt ; &lt;&lt;&lt;&lt;&lt; ρ &lt;&lt;&lt;&lt;&lt;&lt; υ &lt; ό υ ο ο &lt; υ &lt; υ (J ϋ &lt;&lt; ϋ u &lt; ο &lt; ο υ υ ID ϋ ο ϋ υ &lt; υ ο &lt;&lt;&lt; Ρ &lt; ϋ ο υ &lt; ϋ υ ο &lt; o &lt;&lt; U &lt;&lt; ο υ Ρ Ρ ϋ &lt; ϋ tD ρ &lt;&lt; ο &lt; ID &lt; u P &lt; υ &lt; P ο ο &lt; Ο υ ο &lt; ϋ υ &lt; υ &lt; υ Ρ &lt;&lt; υ &lt; υ D υ &lt;; ϋ υ &lt; ϋ υ υ Ο &lt;&lt; 口ο Ρ &lt; 口ο &lt; υ C &lt; ϋ υ υ υ υ uu &lt;口&lt; ο υ Ο ο Ρ ρ υ &lt; ο υ ο υ mouth ο U ϋ ο &lt &lt; u &lt;&lt; υ ο ο υ &lt; υ ϋ &lt; υ &lt;&lt;&lt;&lt;&lt; ο ο &lt; ϋ υ &lt; υ Ο D SEQ ID NO JO r- Os 〇〇in m 00 οο yn ^ Τ) V*) $ m σ\ ιη ιη Os ΟΝ ^Τ) SS ν〇〇\ ro BuΟν sm (Ν Ό CN 〇〇〇〇\ (Ν νο f—^ m cn 152219.doc -73- 201130494

Antisense shares sequence (5'-3 ') CACAGCCAGUCCUCUUACU AUUCCGUAUUACUGCGGUU UUACAGGAGAGGGUAGACA GAAGUCGGCCAAAGUUGUC CAUGCAGCCUCGGGUAUUC ACCUAACUUUGAUGUAAGU AGGCGCAUGUGUGCUAAUC CCACCUAACUUUGAUGUAA SEQ ID NO 636 638 640 642 644 646 648 650 sense shares sequence (5'-3 &quot;) AGUAAGAGGACUGGCUGUG AACCGCAGUAAUACGGAAU UGUCUACCCUCUCCUGUAA GACAACUUUGGCCGACUUC GAAUACCCGAGGCUGCAUG ACUUACAUCAAAGUUAGGU GAUUAGCACACAUGCGCCU UUACAUCAAAGUUAGGUGG SEQ ID NO 635 637 639 3 645 647 OS -74 152219.doc 201130494

〇^ „ •δ- m CN (N o (N CM CN o CN (N (N cn 1—H CN t ^l|J s si I ^ oo CN 2 iTi in v〇卜卜OO OO On On 0's (N (N (N OO (N antisense shares sequence (5'-3 ·) UcAGUcAuAUCCUCGAAcATsT ACUGCGGUUGuAcAGUGAATsT UCUUUUGUcAACGAAGAGATsT GAGGGuAGAcAUUUuACuATsT UGACGcAAGAGUCUUCUGATsT UcAGGuAuAAAGuAAAGCGTsT UGuAuAUuAUcAGUCUGGUTsT UCGAAcAcAGGCUGUCUUUTsT AUUUuACuAUCCUUcAcAGTsT AAAGCGUGUUGUcAAuAAATsT CUCGGGuAUUCUGUuAUGGTsT AuAAAcAUcAUUUCCUUGATsT UGCGGUUGuAcAGUGAAGUTsT uAUUCCGuAUuACUGCGGUTsT AAGAAuAUGAGAUcACUUUTsT UUGAAAGcAUcAUCUUCCUTsT UUUGAGGCGGCUUUCUUUGTsT GUGUUGUcAAuAAAcAUcATsT AAGUuAGUGAGAGUGAAcATsT GAGGCGGCUUUCUUUGUCCTsT UUCCGuAUuACUGCGGUUGTsT GGUUUGAGGCGGCUUUCUUTsT UUCUGAAAGAAuAUGAGAUTsT GCCUCGGGuAUUCUGUuAUTsT cAuAUCCUCGAAcAcAGGCTsT SEQID NO CN VO 654 Ό OO in v〇§ CN 664 VO V〇OO VO VO 670 672 674 676 OO 680 682 684 686 OO OO 1 (N ON v〇1 696 00 Os 700 stock sequence (5'-3〇uGuucGAGGAuAuGAcuGATsT uucAcuGuAcAAccGcAGuTsT ucucuucGuuGAcAAAAGATsT uAGuAAAAuGucuAccc ucTsT ucAGAAGAcucuuGcGucATsT j cGcuuuAcuuuAuAccuGATsT AccAGAcuGAuAAuAuAcATsT AAAGAcAGccuGuGuucGATsT cuGuGAAGGAuAGuAAAAuTsT uuuAuuGAcAAcAcGcuuuTsT ccAuAAcAGAAuAcccGAGTsT ucAAGGAAAuGAuGuuuAuTsT AcuucAcuGuAcAAccGcATsT AccGcAGuAAuAcGGAAuATsT 1 AAAGuGAucucAuAuucuuTsT AGGAAGAuGAuGcuuucAATsT cAAAGAAAGccGccucAAATsT uGAuGuuuAuuGAcAAcAcTsT uGuucAcucucAcuAAcuuTsT GGAcAAAGAAAGccGccucTsT cAAccGcAGuAAuAcGGAATsT AAGAAAGccGccucAAAccTsT AucucAuAuucuuucAGAATsT AuAAcAGAAuAcccGAGGcTsT GccuGuGuucGAGGAuAuGTsT SEQID NO VO m IT) § ON Ό v〇irj v〇VO s 669 673 675 677 679 oo 00 685 Ό 689 § ON 695 697 699 152219.doc -75- 201130494 Η Μ 皞 W - B - ± 1 m inch (N m &lt; Ti CN ri m 00 m inch CN o inch 〇 ON yn m ίη m Μ ^ &lt; 5g 1 name! the OS square the CN _ S \ CN mmm VO VO m »T) On VO VO vo 00 ON VO Os Ό antisense sequence shares (5 · -3 ') uAAAGCGUGUUGUcAAuAATsT GAUGuAAGUuAGUGAGAGUTsT uACUCuAuAAAUcAUGcAGTsT AuAUUCCGuAUuACUGCGGTsT GUcAUcAcAAGGCGcAUGUTsT CGGGuAUUCUGUuAUGGAATsT AuAUGAGAUcACUUUGuAUTsT UUGACGcAAGAGUCUUCUGTsT GCuAAUcAUCUUUCUGGAATsT UUGAUcAAuAUcAGUcAuATsT CUCuAuAAAUcAUGcAGCCTsT GGUUGuAcAGUGAAGUCGGTsT AGGGuAGAcAUUUuACuAUTsT CUUUGAUcAAuAUcAGUcATsT cAGGCGAGGUcAUcAcAAGTsT AuAUcAGUcAuAUCCUCGATsT AAAuAcAGGCGAGGUcAUCTsT AAAuAAACGUGUUuACUCUTsT ACuAUCCUUcAcAGAGAGGTsT UGUUGUcAAuAAAcAUcAUTsT AAGUCGGCcAAAGUUGUCUTsT UCGGGuAUUCUGUuAUGGATsT CGuAUuACUGCGGUUGuACTsT GGCGcAUGUGUGCuAAUcATsT GCGcAUGUGUGCuAAUcAUTsT UUcAGGuAuAAAGuAAAGCTsT UuACUCuAuAAAUcAUGcATsT SEQID NO 〇o Ο o 710 1 712 I 1 714 I 716 718 720 | 722 1 1 724 I 1 726 | oo &lt; N | 730 | | 732 1 734 736 | 738 740 744 746 750 1 752 1 754 Sense strand sequence (5'-3') uuAuuGAcAAcAcGcuuuATsT AcucucAcuAAcuuAcAucTsT cuGcAuGAuuuAuAGAGuATsT ccGcAGnAAuAcGGAAuAuTsT AcA uGcGccuuGuGAuGAcTsT uuccAuAAcAGAAuAcccGTsT AuAcAAAGuGAucucAuAuTsT cAGAAGAcucuuGcGucAATsT uuccAGAAAGAuGAuuAGcTsT uAuGAcuGAnAuuGAucAATsT GGcuGcAuGAuuuAuAGAGTsT ccGAcuucAcuGuAcAAccTsT AuAGuAAAAuGucuAcccuTsT uGAcuGAuAuuGAucAAAGTsT cuuGuGAuGAccucGccuGTsT ucGAGGAuAuGAcuGAuAuTsT GAuGAccucGccuGuAuuuTsT AGAGuAAAcAcGuuuAuuuTsT ccucucuGuGAAGGAuAGuTsT AuGAuGuuuAuuGAcAAcATsT AGAcAAcuuuGGccGAcuuTsT uccAuAAcAGAAuAcccGATsT GuAcAAccGcAGuAAuAcGTsT uGAuuAGcAcAcAuGcGccTsT AuGAuuAGcAcAcAuGcGcTsT GcuuuAcuuuAuAccuGAATsT uGcAuGAuuuAuAGAGuAATsT SEQID NO os Bu 705 707 709 713 BU 717 1 719 1 (N 723 725 727 729 731 m 1 735 1 | 737 | 739 743 1 745 | 1 747 | 749 JO 753 152219.doc -76- 201130494

a W ρ— 〇跻冢 琢-6- Si 00 (N 00 yrt 卜 ON 2 o 卜 ^ ^ &lt; 1IL 爹.S # ^ g Γ Γ CN cn CN 00 〇 00 5: ON On OO 00 &lt; N iT) m CN antisense shares sequence (5Ά) AcAGUGAAGUCGGCcAAAGTsT UcAAuAUUUUcAGGUGGAUTsT _1 AGUGAGAGUGAAcAUuAcATsT UcAUcAAuAUUUUcAGGUGTsT GCGGUUGuAcAGUGAAGUCTsT AGCCUCGGGuAUUCUGUuATsT cAcAGCcAGUCCUCUuACUTsT AUUCCGuAUuACUGCGGUUTsT UuAcAGGAGAGGGuAGAcATsT GAAGUCGGCcAAAGUUGUCTsT cAUGcAGCCUCGGGuAUUCTsT ACCuAACUUUGAUGuAAGUTsT AGGCGcAUGUGUGCuAAUCTsT CcACCuAACUUUGAUGuAATsT SEQID NO 756 758 760 762 1 764 1 OO 770 Bu 776 OO 782 sense shares sequence (5'-3 ') i cuuuGGccGAcuucAcuGuTsT AuccAccuGAAAAuAuuGATsT uGuAAuGuucAcucucAcuTsT cAccuGAAAAuAuuGAuGATsT GAcuucAcuGuAcAAccGcTsT uAAcAGAAuAcccGAGGcuTsT AGuAAGAGGAcuGGcuGuGTsT AAccGcAGuAAuAcGGAAuTsT uGucuAcccucuccuGuAATsT GAcAAcuuuGGccGAcuucTsT GAAuAcccGAGGcuGcAuGTsT AcuuAcAucAAAGuuAGGuTsT GAuuAGcAcAcAuGcGccuTsT uuAcAucAAAGuuAGGuGGTsT SEQID NO 755 _1 1 757 759 VO s 765 | 773 | 1 775_I | 777 | ON Bu 〇〇15 2219.doc -77- 201130494

Human PBMC assay TNF-a 〇ά oao 〇o 〇IFN-a 〇-ddod (N 〇oo stable mouse serum C! (N (N dd3 ύ 00 (N -dd (N CN ON rn o cn inch · &lt NrH 00 v〇T3 dm vd Ό C 00 ro inch οό inch GT; — 飕Μ ♦1 cattle 5 pond: f « genus r. Tf ^ noun § 1 1 average maximum I suppression [%] ON oo V 〇00 &lt;N 00 丨料1 IC20 [nM] 0.00019 0.00057 0.00039 -d ά 0.00046 I 0.00027 I 0.00023 0.00010 I average | IC80 [nM] 0.00800 0.11090 1 0.02554 I 0.07983 0.01675 0.01105 0.02481 0.00764 | Average | IC50 [nM] 1 0.00125 I 0.01031 0.00408 0.00616 0.00239 0.00151 0.00256 0.00082 V ^ Μ φ| ^L· ;W ^ jd | average maximum 1 suppression [%] cs 〇\ 00 00 00 00 oo IC20 [nM] 1 0.00021 1 T3 c | 0.00015 | 0.00048 | 0.00045 | | 0.00021 1 0.00000 0.00000 | Average | IC80 [nM] 1 0.00747 1 0.08252 | 0.02714 | 0.08779 | 0.02645 | | 0.01243 | | 0.04194 1 0.00774 丨 1 1 IC50 [nM] 1 0.00089 1 0.00827 0.00209 0.00561 0.00280 0.00154 0.00157 0.00062 SEQ ID NO: 651/652 653/654 655/656 657/658 659/660 661/ 662 663/664 667/668 152219.doc -78- 201130494

00&lt; SEQ ID No. 786 787 〇〇〇〇789 790 卜m ON 794 795 796 797 00 799 〇§ oo s 00 s oo 804 s oo 806 οο OO § g OO o oo sequence cd dad 0JD s σ3 W) bp o 5 HS) cd s S) cd S) £ 6 8 ob λ 〇苕Η Η Η cd ω) tli) s wear a § cd wear bJO a cj σ3 OX) bfi o I HHH 0 ϋ 钰bi) 05 bJO 1 bC σί kS OJO W) o Goods Cifl 芘Λ Λ cd bfl 穿 wear GO bfl ti 0 HHHHS) cd cd DO C5J) cd bJ} cd g) Si bb bfl σ3 1 ΐό cd § ο 吾 Η Η ο tJ 1 ω钰aaa wear a cd Λ Λ toO cd Λ cd plus ω) ο Η Η Η Η ο ο 芨 cd 芘 cd cd (3) bO cd 〇&gt;4—&gt; Ώ) 8 §8 cd S) bO t2 H 萏Λ Si Ο δ S) a&gt; Ο Ο ο cd 00 CJ) cd s &amp; GO g HHH t: o and cd o cd 00 cd 00 W) 苕cd &amp; — Gp Guide 8 Λ bfi a DO £ HH &amp; s Bp 〇t: o db S 诤8 S) wear ω) white Η Η ο ο 1 S3 8 i U) tb 8 cd a OJO [: H 1 S3 S) ϋ ϋ ο 芘诤υ 努 GO GO 〇β cd S) bfi cd te 8 wear cd aa ο s 5 W) § S) 13 S) 00 occupies HH [: io Si W) 〇Λ cd cd Λ S) 0£l 00 cd dO 00 C3 oo bO Λ &amp; W) tb a § g) 8 | o cd M 8 i broom ts υ ω) DO 芘W) C3 aa 0 cd 〇W) 1 o ti ts from ts s ab tb ω Λ § § B &amp; cd Ώ) c〇cd cd o S) t: o b0 cd Λ 0 1 &amp;0 Λ cd bO b〇a O e wear so bb W) 〇03⁄4 Λ ω) cd OD 叻cd bfi 芘cd total ω) ο 芘ο bb Λ Ο Έ3 Λ G0 cd ο bb cd ο dad a Ώ) CJD Oi) OD 〇b0 cd cd 芘cd ti o cd M dad a op ω o 0 ts ci 1 &amp; wear S) function wu ω ο PJ 〇ω u ω υ ω υ SWW ω W ω ω CQ CQ CQ (Ώ CQ PQ PQ μ-ϊ CQ CQ hJ PQ PQ 0Q FPL name ML18001 hIL18002 hIL18003 hIL 18004 hIL18005 hIL18006 hIL18007 hIL18008 hIL 18009 WL18010 ML18011 WL18012 ML18013 WL18014 WL18015 ML18016 WL18017 hIL18018 ML18019 hIL18020 hIL18021 hIL18022 hIL18023 hIL 18024 WL18025 152219.doc •79- 201130494 6&lt; SEQ ID No. J 00 812 m 00 814 00 00 817 1 00 OO 819 os (N 00 sequence 芘C3 W) Λ s bO ω) § cd bfl 00 00 t3 8. W) § S) § cd ο Η ο aa cd cd cd &amp;0 cd Ofl W) o β H b〇ts o BV oo bO Λ QOOO Ώ) cd wear OJO 1 o | &am p; s &amp; § 8 O &amp;&quot;§) o §8 cd &quot;SW) 00 ο Ή Ή Οΰ 努 W) ω) cd §) tb 8 ω ω bC Ο ο 8 Ο &amp; 00 a Cifl Ο S) W0 W) Lane 00 cd &quot;G § Μ t3 ω oc IW) 8 OW) o W) § cd td &amp; OJO oaasa to cd W) § -4—» Ώ) 0 §8 cd 1 8 ΰ£ QJO ω) tuo o meal DO 00 芘W) another cy〇cd cd W) 芘W) function ω u UW u SW -3 WSS ω ω j U m FPL name hGAPOOl | hGAP002 hGAP003 hGAP004 hGAP005 hGAP006 hGAP007 hGAP008 hGAP009 hGAPOlO | hGAPOll

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Οι&lt; SEQ ID No. (N (N 00 (Ν 00 寸 c 00 &lt; n CN 00 Ό CN oo 00 00 &lt; Ν 00 0's (Ν οο ο m 00 00 (Ν cn 00 s inch m 00 m 00 m 00 P; 00 00 m 00 Os S3 O tb cd cd cd 00 cd bO W) ϋ 苕Η Η Η &amp;〇Οΰ cd ω) Οΰ cd S) cd ο ω) cd Ο ο 1 ο Μ S) Wear ω) (2) Η Η ω) S Si ϋ ω) te 8) s to MS [: HS) cd ω) GD a Ci〇DO § s Si CJ e HHH o to e CJ g W) (3) W) tuo 芘Si ' So W) 0 1 HS) bi) i Gfl Μ &amp; cd s μ ο Ε Η ο i ο a cd i 8 a Η Η S) Μ Sweep US) g) 芘ο 荔S) e Η Sj i, S WD Ϊ a O cd g ϋ g) § s bO HHH 萏 &amp; Ώ) &amp; cd to cd ο ο ο bb S) Η Η Η Η ο I ϋ 1 8 wear bp ci 钰 cd wear ο Si bO υ ΐβ σ3 cd 00 Ή) σ3 Ο 1 W) i) SHHH 5 ω) OJ) Cifl W) square i 8 io C3fl cd a ca 0 ob cd bp HHHH 1 萏 ω) υ λ cd ω) cd ω) cd a ο cd Λ ϋ b ΰ 0 0 0 0 0 0 0 0 DO 萏κί λ t5 bb e ο Ώ) a 1 1 8 cd S) § Ε Η Η Η ο 诖S ω) S cd a S) 芘 ω) cd § Λ 〇 £ ca s cd bO 穿 S) ΰΧ) ti 0 β t Si a λ t: 1 c tsa § ω υ W hJ ω ω U ω υ WU ω W ω 1-1 PQ CQ W ω Η-1 υ ω ω .-l hJ CQ PQ hJ s ω u kJ CU ΕΧι ι-Η Ο 00 CN ϋ α s 00 ear cs Ο Of S 00 S | CN oas 00 S| (N ϋ cx S 00 5 ε丨(Ν Ο σ g 00 ε rV ϋ a 00 3 ε( (Ν ϋ cx g 00 S| (N o σ § 00 2 ε| (Ν ο ο O 00 δ((Ν Ο cx S CN ϋ cy (N OO S( CN oom 00 3 S (Ν ϋ a 00 2 s (N ϋ a S3 hJ ε cs 〇a ν〇00 s (Ν Ο a 00 ε CN Ο ο 00 00 ε CN o σ ON 00 ε ( CN oo 宕 00 (Ν Ο 152 219.doc -81 - 201130494 II&lt; SEQ ID No. 842 m inch Z iTi Z 846 847 〇〇 849 850 00 852 ro 00 854 \T) OO 856 Sequence Λ Ο 1 & cd &amp; bp ω) W) is W) b0 W) 1 1 0 1 〇芘S) ss 3) o S) 0 1 s cd Wear S wog § s Λ so 83 a 8 1 ω) i dO H dO tb bO 8 W) bfi 1 0 S) s cd Si £PO ω) e 0 % 1 o wear S) bO 芘bj〇S) §8 s % MS) a So s 8 S a tb u ΐβ wear cd bfi 容 Si Wl 1 Si ω) Ώ) s Ώ) CJ cd i ό 1 ω ο g 50 1 60 g -w 51 i 8 Λ S) % 00 Ε ο ω) ω) υ 8 S» cd a § c3 S) bO t5 00 8 〇ti W) gg Ώ) S) s S o 目(DD 芘W) Sd op 0 g) Ml 芘cd S) ΰ£) § 8 Ο S) CQ 磬0 1 〇〇W) g) i &amp; 0 function ω ussau ω hi hJ CQ hJ n ω υ ω υ tu ω HJ ω u CQ ω u FPL name (N o XQ &lt; 〇B CN CN ϋ sg ε ro (N os &lt; o B inch 1 CN 〇°1 ffi Q 〇s &lt;N oa ffi' s &lt; 0 s &lt;N oa ffi1 s &lt; 0 B 卜CN 〇a ffi1 Q 〇B 〇〇〇as' Q a ε as (Ν ϋ ο κ1 S &lt; ο ε ο CN Ο a κ1 s &lt; ο ε CN 〇a XQ 〇S &lt;N (N 〇XQ 〇S m CN o Q Oh &lt; 〇ε (N 〇o ε ^T) &lt;N 〇Q Oh &lt; 〇 s

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1 Modified sequence 1 Antisense strand sequence (5'-3,) I UCGUUUUGAAcAGUGAAcAdTsdT ? TJ &lt;&lt; D 〇&lt;&lt;&lt; o _ ou •Ό &lt; ϋ D 〇&lt;&lt;&lt; 0 1 s 〇o. H 1 T3 &lt;&lt;&lt; 〇D 〇&lt;&lt;&lt;&lt; ϋ § ou o. Ό u &lt; SD 〇CJ &lt;&lt; 8 5 2 5 D ey D | UCGUUUUGAAcAGUGAAcAdTsdT I &quot; Ό &lt;&lt;&lt;&lt; 〇o 0 &lt;&lt;&lt; a 1 ou &lt;&lt; 〇D 〇&lt;&lt;&lt; o § cB U a ·〇&lt;&lt;&lt;&lt; 〇D 〇&lt;&lt;&lt; 0 1 O υ Τ3 υ &lt; D Ο υ &lt;&lt; a 2 2 2 DS Η D 1 UCGUUUUGAAcAGUGAAcAdTsdT &lt;&lt; 〇D 〇&lt;&lt;&lt;&lt; 0 1 o υ D. Ό &lt;&lt; o D 〇 &lt;&lt;&lt; 〇§ 3 8 s. H 1 • Ό &lt;&lt;&lt; o D 〇 &lt;&lt;&lt; 0 1 O u H *σ iS u &lt; a 〇S D u &lt; &lt; a 5 2 2 D 8 y D | UUCGUUUUGAAcAGUGAACdTsdT 1 | CUUCGUUUUGAAcAGUGAAdTsdT | I GAAAGuAUCCUUCGuAUGAdTsdT 1 | GAAAGuAUCCUUCGuAUGAdTsdT | I GAAAGUfAUCCUUCGUfAUfOAdTsdT 1 | GAAAGUfAUfCfCfUfUfCfGUfAUfGAdTsdT | | CUuAUuAUcAUGUCCUGGGdTsdT | | CuuAuuAucAUGUCCUGGGdTsdT | I CUfUfAU fUfAUfCfAUGUCCUGGGdTsdT 1 I CuuAuuAucAUGUCCUGGGdTsdT 1 I CfUnjfAUfUfAUfCfAUGUCCUGGGdTsdT ? s 〇〇DUD 〇D &lt; 1 3 &lt; β S 〇o DUD 〇ί D ί 3. D 5 2 u CfUfUfAUaJfAUfCfAUrcUfCfCflJfGGGdTsdT 1 〇〇o D υ DOD $ D iS 2 D l&lt; 2 au GCuAGUCUUCGUUUUGAACdTsdT IH i &lt; 0 1 O yo &lt; δ a H *〇&lt;&lt; 〇i O u B CJ o &lt; δ 宜H s &lt;&lt; e 5 a 2 D ey 2 2 y D 〇 2 uo GCuAGUCUUCGUUUUGAACdTsdT | ξ &lt; 〇I ou B u 3 &lt; O Η &quot;Β &lt;&lt; ο I ο D Β Ο Ο &lt; 5 Η 2 2 υ &lt;&lt; e 2 aa D S3 ya 5 y D 〇5 υ ο GCuAGUCUUCGUUUUGAACdTsdT 1 i 0 1 8 BU 1 a 0 1 O § u &lt; δ % 5 υ &lt;&lt; e 2 3 a D ay 2 ay D 〇6 5 uo UGGCuAUCUUuAuAcAuACdTsdT 1 UfGGCUfAUCUUUfAUfACfAUfACdTsdT | JO 6 DUD § 〇i D υ o SD SEQ ID No &lt;N OO § S 3 ΟΟ ο &lt;N VO OO § 1 436 1 1 .438 I | 440 | L 452 I 1 454 | 1 456 I | 458 II 460 I 1 462 I 464 I OO OO § § s 200 | S fN 204 I 206 1 208 | 210 I 212 I 214 I 482 | 484 | Sense stock sequence (5'-3 uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT | uGuucAcuGuucAAAAcGAdTsdT &lt; a &lt; % &lt; 3 o 0 1 so &lt;&lt;&lt;&lt; 3 〇u &lt; 3 a ξ sg H 2 ϋ &lt;&lt;&lt; 3 〇υ &lt; 3 a and O o &lt;&lt;&lt; 3 c| υ &lt; 3 δ 2 ο Η 1 Ο &lt;&lt;&lt; 3 Ο υ &lt; 3 a ο 1 UfGUfUfCfACaJfGUflJfCfAAAACfGAdTsdT | UfGUfUfCfACajfGURJfCfAAAACfGAdTsdT | UfGUfUfCfACfUfGUfUfCfAAAACfGAdTsdT | UfGUfUfCfACfUfOUfUfCfAAAACfGAdTsdT I UfGUfUfCfACfUfGUfUfCfAAAACfGAdTsdT | GuucAcuGuucAAAAcGAAdTsdT j | uucAcuGuucAAAAcGAAGdTsdT | ucAuAcGAAGGAuAcuuucdTsdT | ucAuAcGAAGGAuAcuuucdTsdT j | ucAuAcGAAGGAuAcuuucdTsdT | | ucAuAcGAAGGAuAcuuucdTsdT | cccAGGAcAuGAuAAuAAGdTsdT [cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | cccAGGAcAuGAuAAuAAGdTsdT | s &lt; &lt; &lt; &lt; billion &lt; &lt; ooso GuucAAAAcGAAGAcuAGcdTsdT | GuucAAAAcGAAG AcuAGcdTsdT | GuucAAAAcGAAGAcuAGcdTsdT | GuucAAAAcGAAGAcuAGcdTsdT | H 2 Έ O &lt;&lt;&lt; o &lt;&lt;&lt;&lt; 3 g Ό 6 &lt;〇&lt; u &lt;&lt; o &lt;&lt;&lt;&lt; 3 Ο [eta] write Έ ο | &lt; ο υ &lt; &lt; and ο Η 3 Έ ο &lt; 3 &lt; ο &lt; &lt; &lt; &lt; ο GUfUfCfAAAACfGAAGACfUfAGCfdTsdT | GUfUfCfAAAACfGAAGACfUfAGCfdTsdT | GUajfCfAAAACfGAAGACfUfAGCfdTsdT | GUfUfCfAAAACfGAAGACfUfAGCfdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT I GuAuGuAuAAAGAuAGccAdTsdT | SEQ ID No 5 «Λ1 in s ϊ〇2 1 435 | 1 437 1 1 439 1 •n 5 1 L_457 1 丨459 | 3 o; S; & § 1-^03 1 ” ! 207 | 209 | 213 | 1 The modified sequence of the antisense strands sequences (5 · -3 ·) | UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA | UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA | UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA 1 UCGUUUUGAACAGUGAACA i i UCGUUUUGAACAGUGAACA | | UCGUUUUGAACAGUGAACA | 1 UCGUUUUGAACAGUGAA CA Π 1 UCGUUUUGAACAGUGAACA | | UUCGUUUUGAACAGUGAAC | 1 CUUCGUUUUGAACAGUGAA | [GAAAGUAUCCUUCGUAUGA | | GAAAGUAUCCUUCGUAUGA | | GAAAGUAUCCUUCGUAUGA | | GAAAGUAUCCUUCGUAUGA | 1 CUUAUUAUCAUGUCCUGGG j I CUUAUUAUCAUGUCCUGGG | | CUUAUUAUCAUGUCCUGGG 1 1 CUUAUUAUCAUGUCCUGGG | i CUUAUUAUCAUGUCCUGGG | 1 CUUAUUAUCAUGUCCUGGG | CUUAUUAUCAUGUCCUGGG | CUUAUUAUCAUGUCCUGGG | CUUAUUAUCAUGUCCUGGG | GCUAGUCUUCGUUUUGAAC \ GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC | GCUAGUCUUCGUUUUGAAC 1 GCUAGUCUUCGUUUUGAAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | SEQ ID No tN (N &lt; N (N fM (N &lt; N &lt; N (Ν ( Ν CN (N CN cs fN v〇OO OO OO OO ooooooooo rs &lt;N (N (N ΓΝ &lt;Ν (Ν N (N rs (N (N N 有 stock sequence (5'-3') 1 UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACG A | UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACGA 1 UGUUCACUGUUCAAAACGA | UGUUCACUGUUCAAAACGA | GUUCACUGUUCAAAACGAA 1 UUCACUGUUCAAAACGAAG 1 UCAUACGAAGGAUACUUUC I 1 UCAUACGAAGGAUACUUUC |! UCAUACGAAGGAUACUUUC 1 | UCAUACGAAGGAUACUUUC 1 CCCAGGACAUGAUAAUAAG |! I CCCAGGACAUGAUAAUAAG | 1 CCCAGGACAUGAUAAUAAG] CCCAGGACAUGAUAAUAAG | CCCAGGACAUGAUAAUAAG | CCCAGGACAUGAUAAUAAG | CCCAGGACAUGAUAAUAAG | CCCAGGACAUGAUAAUAAG | CCCAGGACAUGAUAAUAAG | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUUCAAAACGAAGACUAGC | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | SEQ ID No Ui BU p- pitapat billion \ On On O' o Ov 〇\ o 152219.doc -83- 201130494

Cn ί uGGCuAUCOUuAuAcAuACdTsdT | s &lt;&lt; 1 BO | 1 UfGGCUfAUCUUUfAUfACfAUfACfdTsdT | H 2 u 6 D ί USD i&lt; § i DU 〇i2 D 1 uGGCuAUCUUuAuAcAuAcdTsdT | H s &lt;&lt;&lt;&lt;&lt; iui H s &lt; -1 1 3 0 1 § g H | S &lt;&lt;&lt;&lt; 〇 &lt; CJ oaas ί &lt;&lt; 1 3 〇§ 巨 | CCGAUUUCCUUGGUcAAUGdTsdT | I cCGAUUUCCUUGGUcAAuGdTsdT | I CfCGAUUUCCUUGGUCfAAUfGdTsdT | HIS 3 &lt;&lt; 1 § § &lt; ϋ U LV (- 1 QD 1 § y _ g | CfCfGAUOJfUfCfCaJfUfGGUfCfAAUfGdTsdT | | UCCUGCGAcAAAuAGUUUGdTsdT | | UfCCUGCGACfAAAUfAGUUUfGdTsdT | e § O ί D &lt;&lt; U ouo D uy DI UCCUGCGAcAAAuAGUUUGdTsdT | 1 0 1 o &lt;&lt; &lt o 8 DU Ϊ | UfCCUfGCGACfAAAUfAGUUUfGdTsdT | H | § OD &lt;&lt; ί U ou QDU y Q | uCCuGCGAcAAAuAGLTUuGdTsdT | Ο i ο &lt;&lt;&lt;&lt;&lt; ο υ ο ϋ 1 &lt;&lt;&lt; 1 ϋ υ ϋ 1 UGUUCUcAcAGGAGAGAGUdTsdT | 1 UfGUUCUCfACfAGGAGAGAGUfdTsdT | ID Ο &lt; Ο &lt; ϋ &lt; 8 CJ Β ai | UGUUCUcAcAGGAGAGAGUdTsdT | H •σ a &lt; o &lt; a &lt; s &lt;&lt; (J g 〇g | UfGUfUCUCfACfAGGAGAGAGUfdTsdT | Ξ D 〇&lt; o &lt; o &lt; oou l&lt; u D u 2 D s DI UGUUCUcAcAGGAGAGAGUdTsdT | 泽Ό 〇&lt; o &lt; o &lt; 8 | DU δ Ά | UfGUUCUCfACfAGGAGAGAGUfdTsdT | ID ϋ &lt; o &lt; ο &lt; ο ο ι&lt; υ 5S υ δ § 9 D | UGUUCUcAcAGGAGAGAGUdTsdT | HI 〇&lt; o &lt; 0 &lt; 8 &lt; 1 u B 〇| UfGUfUCUCfACfAGGAGAGAGUfdTsdT | H 1 s D ϋ &lt; 〇 &lt; o &lt; oo 6 u ί u D u 2 D a Q | UGUUCUcAcAGGAGAGAGUdTsdT | H 1 〇δ &lt; o &lt; o &lt; o ϋ &lt;&lt; U 3 〇 Giant H 1 o &lt; a &lt; ο &lt; gu iS u DU g S o ? SD 〇&lt; o &lt; o &lt; oou i&lt; y 5 y 2 oe DD 〇&lt; o &lt; o &lt; oou δ δ B es Ξ D 〇&lt; o &lt 0 &lt; 8 ί u S y 2 y 5 D 1 | AAAGCGuAUUGUcAAuAAAdTsdT | I AGUUUGUUGCGAGAGGAAGdTsdT | SEQ ID No § ss 8 s Ό 5 is〇? § 00 (N § o vs. N inch VO S S (Ν &lt;Ν &lt;Ν ίΝ 1 g 00 o (N vt s〇00 vj (N 泠CN 00 &lt;N CM 沄fN CM CN CN NO (N 00 ΓΟ (N § rs 5 Γ4 00 In GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT |! GuAuGuAuAAAGAuAGccAdTsdT | I GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | GuAuGuAuAAAGAuAGccAdTsdT | I cAuuGAccAAGGAAAucGGdTsdT 1 I cAuuGAccAAGGAAAucGGdTsdT | I cAuuGAccAAGGAAAucGGdTsdT | | cAuuGAccAAGGAAAucGGdTsdT _ | 1 cAuuGAccAAGGAAAucGGdTsdT 1 t cAuuGAccAAGGAAAucGGdTsdT | | cAAAcuAuuuGucGcAGGAdTsdT | I cAAAcuAuuuGucGcAGGAdTsdT | | cAAAcuAuuuGucGcAGGAdTsdT | | cAAAcuAuuuGucGcAGGAdTsdT | I cAAAcuAuuuGucGcAGGAdTsdT | 1 cAAAcuAuuuGucGcAGGAdTsdT | | cAAAcuAuuuGucGcAGGAdTsdT | I cAAAcuAuuuGucGcAGGAdTsdT | 1 cAAAcuAuuuGucGcAGGAdTsdT 1 Η 1 • Ό Ο ο &lt; ο around &lt; Η • s ο 1 AcucucuccuGuGAGAAcAdTsdT I 1 AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdTsdT | I AcucucuccuGuGAGAAcAdTsdT I AcucucuccuGuGAGAAcAdTsdT I AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT I AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT 1 AcucucuccuGuGAGAAcAdT sdT I AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT I AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT | AcucucuccuGuGAGAAcAdTsdT &lt; billion &lt; o 0 υ § 3 1 S o H 1 &lt; &lt; &lt; 0 &lt; s § § 3 f 1 | ACnjfCftjfCnjfCfCfUfGUfGAGAACfAdTsdT 1 ACfUfCfUfCfUfCfCfUfGUfGAGAACfAdTsdT; | uuuAuuGAcAAuAcGcuuudTsdT _ cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu cu N fN (N δ &lt; N (S (N &lt; N m ΓΝ fS fN &lt; ίπ &lt; UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | UGGCUAUCUUUAUACAUAC | CCGAUUUCCUUGGUCAAUG | CCGAUUUCCUUGGUCAAUG | CCGAUUUCCUUGGUCAAUG | CCGAUUUCCUUGGUCAAUG | CCGAUUUCCUUGGUCAAUG | CCGAUUUCCUUGGUCAAUG | UCCUGCGACAAAUAGUUUG | UCCUGCGACAAAUAGUUUG | 1 onnnovnvvvDvoDonDon UCCUGCGACAAAUAGUUUG | ;UCCUGCGAC AAAUAGUUUG | i UCCUGCGACAAAUAGUUUG |: UCCUGCGACAAAUAGUUUG | I UCCUGCGACAAAUAGUUUG | 1 UCCUGCGACAAAUAGUUUG | 1 UCCUGCGACAAAUAGUUUG | 1 UGUUCUCACAGGAGAGAGU | 1 UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | | UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | 1 UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | 1 UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | | UGUUCUCACAGGAGAGAGU | 1 UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | | UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | | UGUUCUCACAGGAGAGAGU | I UGUUCUCACAGGAGAGAGU | | AAAGCGUAUUGUCAAUAAA | 1 AGUUUGUUGCGAGAGGAAG | SEQ ID No tj- TT 00 inch SO o NO v〇Ό 00 00 00 00 00 00 00 00 s SSS (N (N δ: m GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAGAUAGCCA | GUAUGUAUAAAG AUAGCCA | CAUUGACCAAGGAAAUCGG | CAUUGACCAAGGAAAUCGG |! CAUUGACCAAGGAAAUCGG | CAUUGACCAAGGAAAUCGG |! CAUUGACCAAGGAAAUCGG | j CAUUGACCAAGGAAAUCGG | | CAAACUAUUUGUCGCAGGA | I CAAACUAUUUGUCGCAGGA | | CAAACUAUUUGUCGCAGGA | 1 CAAACUAUUUGUCGCAGGA | I CAAACUAUUUGUCGCAGGA | 1 CAAACUAUUUGUCGCAGGA | 1 CAAACUAUUUGUCGCAGGA 1 1 CAAACUAUUUGUCGCAGGA | 1 CAAACUAUUUGUCGCAGGA 1 1 CAAACUAUUUGUCGCAGGA | 1 ACUCUCUCCUGUGAGAACA | 1 ACUCUCUCCUGUGAGAACA | I ACUCUCUCCUGUGAGAACA | | ACUCUCUCCUGUGAGAACA | I ACUCUCUCCUGUGAGAACA 1 I ACUCUCUCCUGUGAGAACA 1 I ACUCUCUCCUGUGAGAACA | 1 ACUCUCUCCUGUGAGAACA | 1 ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA_i [ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA |! ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA I ACUCUCUCCUGUGAGAACA l ACUCUCUCCUGUGAGAACA 1 ACUCUCUCCUGUGAGAACA | UUUAUUGACAAUACGCUUU | CUUCCUCUCGCAACAAACU SEQ ID No r·» r*1 m •a «Λ r- 卜卜r- 卜卜卜r- 卜σν Os Os On Os Os ON On On Os On 〇\ O' 〇s On Os On fN -84- 152219.doc 201130494

β: h Co 1 ACUuAuAAuAAAuAUGGUCdTsdT II AGGCCGAUUUCCUUGGUcAdTsdT IH β 〇〇BUB 〇U oo &lt; H 1 •Ό ϋ o D y § &lt; ϋ u § &lt; 1 -〇D 〇S 3 5 yy 2 a D &lt; eyuoo &lt I AGGCCGAUUUCCUUGGUcAdTsdT | HI 〇1 u 1 3 &lt; o § o &lt; 0 〇〇u 1 &lt; O § oa Ό D 〇Q 5 2 yy 2 5 d &lt; ΰ oat 1 AGGCCGAUUUCCUUGGUcAdTsdT | H aogu § 3 &lt; a 〇oo &lt; H 1 8 5 ui &lt; OU ϋ 〇 &lt; Ό £=i D 〇e 2 2 yyaa D &lt; s O &lt; | uAGCuAGUCUUCGUUUUGAdTsdT | I CUUCGuAUGAUGAAGAUUCdTsdT | H ? g &lt;&lt;&lt; D g &lt; 〇u | I *5 &lt; o &lt;&lt; o D &lt; 〇D &lt; (3 uo S ϋ a D &lt; e &lt; a D ey 2 2 u | CUUCGuAUGAUGAAGAUUCdTsdT | *O i &lt; o &lt; o &lt; S &lt; c3 uoo H 1 &lt; 〇 &lt;&lt; o D &lt; 〇o 3 8 D 3 a H 1 S ya D &lt; e D &lt; e D ey 2 Au | CUUCGuAUGAUGAAGAUUCdTsdT | 1 og &lt; 〇 &lt;&lt; 0 D &lt; ϋ D &lt; U 1 H 1 w &lt; 〇 &lt;&lt; o D &lt; 〇D &lt; u 3 ya D &lt;〇&lt;&lt; SD &lt; a D 芑DQ y 2 2 u I AAcAUuAuAGA UCuAUCCCdTsdT 1 I UuAUUCCUGCGAcAAAuAGdTsdT | I AGUcAuAUCUUcAAAuAGAdTsdT I o &lt;&lt;&lt; 5 D &lt;&lt; D 〇&lt;&quot;Ό o SD &lt;&lt; ί y 2 ay DD yd O &lt; AGUcAuAUCUUcAAAuAGAdTsdT | H o &lt &lt;&lt;&lt;&lt; D a D &lt;&lt; D 〇&lt; β •Ό 〇o &lt;&lt; y. a 5 y DDD 〇&lt; AGUcAuAUCUUcAAAuAGAdTsdT | ϋ &lt;&lt;&lt;&lt;&lt; D 5 D &lt; &lt; D square &lt; HU 5 D &lt; &lt; y 2 2 D 6 D s O &lt; UGCGAcAAAuAGUUUGUUGdTsdT | UCCUUCGuAUGAUGAAGAUdTsdT | AAAuAGUUUGUUGCGAGAGdTsdT | UUCGuAUGAUGAAGAUUcAdTsdT | AAGCGAUCUGGAAGGUCUGdTsdT | UGCGAGAGGAAGCGAUCUGdTsdT | GUuAcAGCcAuACCUCuAGdTsdT | AAGCGuAUUGUcAAuAAAUdTsdT | AuAAAGuAAAGCGuAUUGUdTsdT | GCuAGAAAGuAUCCUUCGUdTsdT | UGcACUGGGAGAcAAUUCCdTsdT | SEQ ID No &lt;N ΙΛί (N yn (N Ν 00 CN S fN &lt; N (N ig (N s o fN CN rs rs Ό (N OO &lt;N 〇OO (N &lt;NZ (N 没(N 00 OO fS冢(N &lt;N falling cs fN 茬(N 〇S s 00 o fN mm OO mo (N mv〇(N 00 (N m § (N v〇ΓΛ m 00 o QJ h Cn | GAccAuAuuuAuuAuAAGudTsdT | uGAccAAG GAAAucGGccudTsdT | uGAccAAGGAAAucGGccudTsdT "ΰϋ ccAAGGAAAucGGccudTsdT | uGAccAAGGAAAucGGccudTsdT H 1 •Ό os 〇3 &lt; oo &lt;&lt; % so H 3 *〇us 〇s &lt;&lt;&lt;〇〇&lt;&lt; υ % 〇H 2 • Ό 〇8 u &lt; thousand and &lt; i ο H · 〇〇1 &lt; &lt; oa &lt;? BP o rUfOACfCfAAGGAAAUfCfOGCiCfUfdTsdT rUfOACfCfAAGGAAAUfCfOGCfCaifdTsdT | UfGACfCfAAGGAAAUfCfGGCfCfUfdTsdT | UfGACfCfAAGGAAAUfCfGGCfCOJfdTsdT | ucAAAAcGAAGAcuAGcuAdTsdT | GAAucuucAucAuAcGAAGdTsdT iGAAucuucAucAuAcGAAGdTsdT i | GAAucuucAucAuAcGAAGdTsdT | GAAucuucAucAuAcGAAGdTsdT f- &lt; &lt; 3 &lt; 3 &lt; ! ο &lt;&lt;&lt; 1 υ 1 3 A so H 3 S &lt;&lt; 〇 &lt;&lt; 3 &lt; 3 U 1 and so &lt;&lt; 0 &lt;&lt; 3 &lt ; 3 U 1 spot 2 o [GAAUfCfUaJfCfAUfCfAUfACfGAAGdTsdT | rGAAUfCfUfUfCfAUfCfAUfACfGAAGdTsdT | | GAAUfCfUfUfCfAUfCfAUfACfGAAGdTsdT | rGAAUfCfUfUfCfAUfCfAUfACfGAAGdTsdT | fGGGAuAGAucuAuAAuGuudTsdT | cuAuuuGucGcAGGAAuAAdTsdT | rucuAuuuGAAGAuAuGAcudTsdT | ucuAuuuGAAGAuAuGAcudTsdT | ucuAuuuGAAGAuAuGA cudTsdT | H 1 o &lt;&lt; o &lt; o 3 &lt; u 芝 o H 3 ό a &lt;&lt; a &lt; δ 3 3 &lt; X & so ί- Ι | o &lt;&lt; o &lt; o 3 &lt; shape (- so UfCajfAUfUfUfGAAGAUfAUfGACfUfdTsdT | UfCfUfAUfUOJfGAAGAUfAUfOACfUfdTsdT | UfCfUfAUfUfUfGAAGAUfAUfGACfUfdTsdT | cAAcAAAcuAuuuGucGcAdTsdT | AucuucAucAuAcGAAGGAdTsdT | cucucGcAAcAAAcuAuuudTsdT | uGAAucuucAucAuAcGAAdTsdT | cAGAccuuccAGAucGcuudTsdT | cAGAucGcuuccucucGcAdTsdT | cuAGAGGuAuGGcuGuAAcdTsdT | AuuuAuuGAcAAuAcGcuudTsdT I AcAAuAcGcuuuAcuuuAudTsdT | AcGAAGGAuAcuuucuAGcdTsdT | GGAAuuGucucccAGuGcAdTsdT | SEQ ID No «λ fN (N (N δ On * λ & gt fS &lt;N IS (N i〇(N Os Ό &lt;N 卜&lt;N σ\ &lt;N 00 (N cn 00 &lt;N 00 fN £ &lt;N s &lt;N c?s cs S CN CU 〇 s rs § o &lt;N s ΓΛ σ\ sm wi rn CM &lt;N CN CS Os (N f*·» ro CO r*» 〇\ 5 戟4 ίη 鳟| ACUUAUAAUAAAUAUGGUC | AGGCCGAUUUCCUUGGUCA | AGGCCGAUUUCCUUGGUCA 1 AGGCCGAUUUCCUUGGUCA AGGCCGAUUUCCUUGGUCA I AGGCCGAUUUCCUUGGUCA | AGGCCGAUUUCCUUGGUCA | AGGCCGAUUUCCUUGGUCA | I AGGCCGAUUUCCUUGGUCA | 1 AGGCCGAUUUCCUUGGUCA I AGGCCGAUUUCCUUGGUCA | AGGCCGAUUUCCUUGGUCA | | AGGCCGAUUUCCUUGGUCA | | UAGCUAGUCUUCGUUUUGA j ΓCUUCGUAUGAUGAAGAUUC | | CUUCGUAUGAUGAAGAUUC | | CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | 1 CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | | CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | I CUUCGUAUGAUGAAGAUUC | I AACAUUAUAGAUCUAUCCC | | UUAUUCCUGCGACAAAUAG | 1 AGUCAUAUCUUCAAAUAGA | I AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | AGUCAUAUCUUCAAAUAGA | UGCGACAAAUAGUUUGUUG | UCCUUCGUAUGAUGAAGAU | AAAUAGUUUGUUGCGAGAG | UUCGUAUGAUGAAGAUUCA | AAGCGAUCUGGAAGGUCUG | UGCGAGAGGAAGCGAUCUG | GUUACAGCCAUACCUCUAG | AAGCGUAUUGUCAAUAAAU | AUAAAGUAAAGCGUAUUGU | GCUAGAAAGUAUCCUUCGU | UGCACUGGGAGACAAUUCC | SEQ ID No NO &lt;N OO 00 &lt;N 00 &lt;N 00 (N 00 (N 00 cs 00 (N 00 ΓΜ 〇〇 &lt;N 〇〇(N 〇〇(N 00 fN Pi(N fN cn (N cn &lt;N &lt;N &lt;N fN (N f nN (N 00 m 00 CO 00 00 00 CO 〇〇00 00 00 CO o &lt; N • n 5: 00 s | GACCAUAUUUAUUAUAAGU 1 UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU | UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU | UGACCAAGGAAAUCGGCCU | UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU | UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU 1 UGACCAAGGAAAUCGGCCU | UGACCAAGGAAAUCGGCCU | UCAAAACGAAGACUAGCUA 1 GAAUCUUCAUCAUACGAAG [GAAUCUUCAUCAUACGAAG | GAAUCUUCAUCAUACGAAG | I GAAUCUUCAUCAUACGAAG | | GAAUCUUCAUCAUACGAAG | | GAAUCUUCAUCAUACGAAG | | GAAUCUUCAUCAUACGAAG | I GAAUCUUCAUCAUACGAAG | I GAAUCUUCAUCAUACGAAG | | GAAUCUUCAUCAUACGAAG] I GAAUCUUCAUCAUACGAAG | | GAAUCUUCAUCAUACGAAG | I GGGAUAGAUCUAUAAUGUU] | CUAUUUGUCGCAGGAAUAA | I UCUAUUUGAAGAUAUGACU |! UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGACU | UCUAUUUGAAGAUAUGA CU | CAACAAACUAUUUGUCGCA | AUCUUCAUCAUACGAAGGA | CUCUCGCAACAAACUAUUU | UGAAUCUUCAUCAUACGAA | CAGACCUUCCAGAUCGCUU | CAGAUCGCUUCCUCUCGCA | CUAGAGGUAUGGCUGUAAC | AOUUAUUGACAAUACGCUU | ACAAUACGCUUUACUUUAU | ACGAAGGAUACUUUCUAGC | GGAAUUGUCUCCCAGUGCA |! SEQ ID No XTi fS fN (NR (N (N ss n fs fs On (N cn cn ΓΛ m UI P ; Pi P; P; P; P; P; square \ jn § w- &gt; Bu m 152219.doc -85- 201130494 δ: single my Bookbag Help Co CCCGAAGCUGUGuAGACUGdTsdT | AAAGuAUCCUUCGuAUGAUdTsdT | UCGuAUGAUGAAGAUUcAAdTsdT | CGuAUGAUGAAGAUUcAAAdTsdT] GUUGCGAGAGGAAGCGAUCdTsdT | I AuAGUuAcAGCcAuACCUCdTsdT | I UuAUuAUcAUGUCCUGGGAdTsdT | 1 CUUCCCGAAGCUGUGuAGAdTsdT | I cAAAuAGUUUGUUGCGAGAdTsdT | 1 UCCGGAGUGcAAGUGAUUCdTsdT | I GACUGAuAAUUuAGAUUcAdTsdT | I GAUGUuAUcAGGAGGAUUCdTsdT | I uAGUuAcAGCcAuACCUCUdTsdT | | uAUuAUcAUGUCCUGGGACdTsdT | | UUGuAUCCUUGAUGUuAUCdTsdT | I CCUGCGAcAAAuAGUUUGUdTsdT | | cAAGCuAGAAAGuAUCCUUdTsdT | | CCGGcAUGAAAUUUuAAuAdTsdT | | cAuACCUCuAGGCUGGCuAdTsdT | I UCuACUGGUUcAGcAGCcAdTsdT | | CCGGAGUGcAAGUGAUUCUdTsdT] | CCCGGcAUGAAAUUUuAAUdTsdT | I CGAAGCUGUGuAGACUGcAdTsdT | I AcAGUGAAcAUuAuAGAUCdTsdT | | CCGAAGCUGUGuAGACUGCdTsdT | I GCCCGGcAUGAAAUUUuAAdTsdT | | CUGCGAcAAAuAGUUUGUUdTsdT | | AGCGuAUUGUcAAuAAAUUdTsdT | | GCGCCCGGcAUGAAAUUUUdTsdT | 1 AGGGcAUGCGUcACuAcACdTsdT | 1 GCGuAUUGUcAAuAAAUUUdTsdT | | GCCGAUUUCCUUGGUcAAUdTsdT | ΓGAGGGcAUGCGUcACuAcAdTsdT | | uAuAAuAAAuAUGGUCCGGdTsdT | t CcAuACCUCuAGGCUGGCUdTsdT | [UGAGGGcAUGCGUcACuACdTsdT | | GGGAUUGAGGGcAUGCGUCdTsdT | | CCUUCGuAUGAUGAAGAUUdTsdT | 1 cAAAuAGAGGCCGAUUUCCdTsdT | ΓAGCGAUCUGGAAGOUCUGAdTsdT | | cAGUcAGAAUcAGUcAuAUdTsdT | 1 CUCuACCUCCGGAGUGcAAdTsdT | 1 UCuACCUCCGGAGUGcAAGdTsdT | | GGAUUGAGGGcAUGCGUcAdTsdT | SEQ Π &gt; Νο M mo »nm rs 2 00 in ΓΛ § &lt; N 1 00 VO ro om CN P; s〇00 g (N 00 cn cn s〇00 ro 00 00 o 〇s (S 〇\ m 5 mv〇O' 00 ss 1 1 o rs to 00 inch rN § 5 00 ri 5 inch 5 Cn cAGucuAcAcAGcuucGGGdTsdT | AucAuAcGAAGGAuAcuuudTsdT I uuGAAucuucAucAuAcGAdTsdT | uuuGAAucuucAucAuAc GdTsdT I GAucGcuuccucucGcAAcdTsdT | GAGGuAuGGcuGuAAcuAudTsdT | ucccAGGAcAuGAuAAuAAdTsdT I ucuAcAcAGcuucGGGAAGdTsdT I ucucGcAAcAAAcuAuuuGdTsdT I GAAucAcuuGcAcuccGGAdTsdT I:! UGAAucuAAAuuAucAGucdTsdT I GAAuccuccuGAuAAcAucdTsdT | AGAGGuAuGGcuGuAAcuAdTsdT | GucccAGGAcAuGAuAAuAdTsdT | GAuAAcAucAAGGAuAcAAdTsdT I AcAAAcuAuuuGucGcAGGdTsdT | AAGGAuAcuuucuAGcuuGdTsdT | I uAuuAAAAuuucAuGccGGdTsdT | uAGccAGccuAGAGGuAuGdTsdT | I uGGcuGcuGAAccAGuAGAdTsdT II AGAAucAcuuGcAcuccGGdTsdT | | AuuAAAAuuucAuGccGGGdTsdT | | uGcAGucuAcAcAGcuucGdTsdT | 1 GAucuAuAAuGuucAcuGudTsdT | I GcAGucuAcAcAGcuucGGdTsdT I | uuAAAAuuucAuGccGGGcdTsdT | I AAcAAAcuAuuuGucGcAGdTsdT | I AAuuuAuuGAcAAuAcGcudTsdT | | AAAAuuucAuGccGGGcGcdTsdT | | GuGuAGuGAcGcAuGcccudTsdT I AAAuuuAuuGAcAAuAcGcdTsdT 1 | AuuGAccAAGGAAAucGGcdTsdT 1 uGuAGuGAcGcAuGcccucdTsdT 1 ccGGAccAuAuuuAuuAuAdTsdT | AGccAGccuAGAGGuAuGGdTsdT 1 GuAGuGAcGcAuGcccucAdTsdT I GAcGcAuGcccucAAucccdTsdT | AAucuucAucAuAcGAAGGdTsdT | GGAAAucGGccucuAuuuGdTsdT | ucAGAccuuccAGAu cGcudTsdT | AuAuGAcuGAuucuGAcuGdTsdT | uuGcAcuccGGAGGuAGAGdTsdT I cuuGcAcuccGGAGGuAGAdTsdT | uGAcGcAuGcccucAAuccdTsdT SEQ ID No 〇 〇 \ «η ΙΛ Wi ri Os Ό \〇Pi «Λ P; m 00 CO m 00 00 ro σ' 〇〇ΓΛ 〇ΙΛ 〇〇 \ o 〇o inch 1 inch r- O 'begins § § 5 Validity 9 Cn &lt; Μ CCCGAAGCUGUGUAGACUG I AAAGUAUCCUUCGUAUGAU I UCGUAUGAUGAAGAUUCAA I CGUAUGAUGAAGAUUCAAA I GUUGCGAGAGGAAGCGAUC | 1 AUAGUUACAGCCAUACCUC II UUAUUAUCAUGUCCUGGGA II CUUCCCGAAGCUGUGUAGA II CAAAUAGUUUGUUGCGAGA II UCCGGAGUGCAAGUGAUUC II GACUGAUAAUUUAGAUUCA I t GAUGUUAUCAGGAGGAUUC | | UAGUUACAGCCAUACCUCU II UAUUAUCAUGUCCUGGGAC | I UUGUAUCCUUGAUGUUAUC II CCUGCGACAAAUAGUUUGU II CAAGCUAGAAAGUAUCCUU | I CCGGCAUGAAAUUUUAAUA | 1 CAUACCUCUAGGCUGGCUA | I UCUACUGGUUCAGCAGCCA I | CCGGAGUGCAAGUGAUUCU | I CCCGGCAUGAAAUUUUAAU | I CGAAGCUGUGUAGACUGCA | I ACAGUGAACAUUAUAGAUC II CCGAAGCUGUGUAGACUGC II GCCCGGCAUGAAAUUUUAA | I CUGCGACAAAUAGUUUGUU I 1 AGCGUAUUGUCAAUAAAUU II GCGCCCGGCAUGAAAUUUU | I AGGGCAUG CGUCACUACAC | 1 GCGUAUUGUCAAUAAAUUU I | GCCGAUUUCCUUGGUCAAU | I GAGGGCAUGCGUCACUACA JI UAUAAUAAAUAUGGUCCGG 1 I CCAUACCUCUAGGCUGGCU | I UGAGGGCAUGCGUCACUAC 1 1 GGGAUUGAGGGCAUGCGUC 1 I CCUUCGUAUGAUGAAGAUU | I CAAAUAGAGGCCGAUUUCC I AGCGAUCUGGAAGGUCUGA | CAGUCAGAAUCAGUCAUAU | CUCUACCUCCGGAGUGCAA I UCUACCUCCGGAGUGCAAG | GGAUUGAGGGCAUGCGUCA SEQ ID No s 00 SO o fS v〇00 S 00 00 s 00 ON osso &lt; N \ 〇00 Pi 00 o 5 y Cn CAGUCUACACAGCUUCGGG AUCAUACGAAGGAUACUUU I UUGAAUCUUCAUCAUACGA I UUUGAAUCUUCAUCAUACG GAUCGCUUCCUCUCGCAAC GAGGUAUG &lt; 3CUGUAACUAU I UCCCAGGACAUGAUAAUAA I UCUACACAGCUUCGGGAAG I UCUCGCAACAAACUAUUUG I GAAUCACUUGCACUCCGGA I UGAAUCUAAAUUAUCAGUC I GAAUCCUCCUGAUAACAUC I AGAGGUAUGGCUGUAACUA I GUCCCAGGACAUGAUAAUA I i GAUAACAUCAAGGAUACAA I ACAAACUAUUUGUCGCAGG I! AAGGAUACUUUCUAGCUUG II UAUUAAAAUUUCAUGCCGG I ! UAGCCAGCCUAGAGGUAUG II UGGCUGCUGAACCAGUAGA II AGAAUCACUUGCACCCCGG 1 I AUUAAAAUUUCAUGCCGGG I 1 UGCAGUCUACACAGCUUCG I | GAUCUAUAAUGUUCACUGU II GCAGUCU ACACAGCUUCGG I UUAAAAUUUCAUGCCGGGC I AACAAACUAUUUGUCGCAG II AAUUUAUUGACAAUACGCU II AAAAUUUCAUGCCGGGCGC II GUGUAGUGACGCAUGCCCU II AAAUUUAUUGACAAUACGC i AUUGACCAAGGAAAUCGGC 1 I UGUAGUGACGCAUGCCCUC | I CCGGACCAUAUUUAUUAUA Shu AGCCAGCCUAGAGGUAUGG I GUAGUGACGCAUGCCCUCA GACGCAUGCCCUCAAUCCC AAUCUUCAUCAUACGAAGG I GGAAAUCGGCCUCUAUUUG I UCAGACCUUCCAGAUCGCU AUAUGACUGAUUCUGACUG UUGCACUCCGGAGGUAGAG 1 CUUGCACUCCGGAGGUAGA 1 UGACGCAUGCCCUCAAUCC SEQ ID No Ό * r \ Ό 5 S | Λ square &gt; 00 00 00 〇\ 00 5; Os «/&gt; 〇\ 5 g: ossg - 卜〇\ (N m •86-

152219.doc 201130494

ει &lt; 1 modified sequence of the antisense strands sequences (5 · -3 ·) | UcAGUcAuAUCCUCGAAcATsT | | ACUGCGGUUGuAcAGUGAATsT | | UCUUUUGUcAACGAAGAGATsT | | GAGGGuAGAcAUUUuACuATsT | | UGACGcAAGAGUCUUCUGATsT | | UcAGGuAuAAAGuAAAGCGTsT | | UGuAuAUuAUcAGUCUGGUTsT | | UCGAAcAcAGGCUGUCUUUTsT | | AUUUuACuAUCCUUcAcAGTsT | | AAAGCGUGUUGUcAAuAAATsT | | CUCGGGuAUUCUGUuAUGGTsT | | AuAAAcAUcAUUUCCUUGATsT | | UGCGGUUGuAcAGUGAAGUTsT | | uAUUCCGuAUuACUGCGGUTsT | | AAGAAuAUGAGAUcACUUUTsT | | UUGAAAGcAUcAUCUUCCUTsT | | UUUGAGGCGGCUUUCUUUGTsT | | GUGUUGUcAAuAAAcAUcATsT | [AAGUuAGUGAGAGUGAAcATsT | | GAGGCGGCUUUCUUUGUCCTsT | | UUCCGuAUuACUGCGGUUGTsT | | GGUUUGAGGCGGCUUUCUUTsT | UUCUGAAAGAAuAUGAGAUTsT | GCCUCGGGuAUUCUGUuAUTsT | cAuAUCCUCGAAcAcAGGCTsT | uAAAGCGUGUUGUcAAuAATsT | GAUGuAAGUuAGUGAGAGUTsT | uACUCuAuAAAUcAUGcAGTsT | AuAUUCCGuAUuACUGCGGTsT | GUcAUcAcAAGGCGcAUGUTsT | CGGGuAUUCUGUuAUGGAATsT I AuAUGAGAUcACUUUGuAUTsT | UUGACGcAAGAGUCUUCUGTST | GCuAAUcAUCUUUCUGGAATsT SEQ ID NO | 652 | 654 | 656 | 658 | 660 s〇VO | 664 | 666 ί 00 vo 1 670 1 672 | 1 674 | 1 676 | 1 678 | | 680 | 1 682 | | 684 | | 686 | I 688 | 〇os (N Os VO 694 | 1 696 | 1 698 | 700 | 702 | oooo Bu (N 00 Bu Bu Bu Youyi inch r- v〇 shares sequence (5'-3 ') | uGuucGAGGAuAuGAcuGATsT | uucAcuGuAcAAccGcAGuTsT | ucucuucGuuGAcAAAAGATsT | uAGuAAAAuGucuAcccucTsT | ucAGAAGAcucuuGcGucATsT | cGcuuuAcuuuAuAccuGATsT | AccAGAcuGAuAAuAuAcATsT | AAAGAcAGccuGuGuucGATsT | cuGuGAAGGAuAGuAAAAuTsT | uuuAuuGAcAAcAcGcuuuTsT | ccAuAAcAGAAuAcccGAGTsT | ucAAGGAAAuGAuGuuuAuTsT | | AcuucAcuGuAcAAccGcATsT | | AccGcAGuAAuAcGGAAuATsT | | AAAGuGAucucAuAuucuuTsT | | AGGAAGAuGAuGcuuucAATsT | | cAAAGAAAGccGccucAAATsT | | uGAuGuuuAuuGAcAAcAcTsT | | uGuucAcucucAcuAAcuuTsT | GGAcAAAGAAAGccGccucTsT | cAAccGcAGuAAuAcGGAATsT | AAGAAAGccGccucAAAccTsT | 1 AucucAuAuucuuucAGAATsT | AuAAcAGAAuAcccGAGGcTsT | GccuGuGuucGAGGAuAuGTsT | uuAuuGAcAAcAcGcuuuATsT | AcucucAcuAAcuuAcAucTsT | cuGcAuGAuuuAuAGAGuATsT | ccGcAGuAAuAcGGAAuAuTsT | AcAuGcGccuuGuGAuGAcTsT | uuccAuAAcAGAAuAcccG TsT | AuAcAAAGuGAucucAuAuTsT | cAGAAGAcucuuGcGucAATsT | uuccAGAAAGAuGAuuAGcTsT | SEQ ID NO «Π | 655 | 657 〇\ | 663 | 669 | P VO «η 1 677 | 1 679 | im 00 •n 00 vo 1 687 1 Os OO Ό $ os VO ό 〇\ Ό 1 697 1 ON Os v〇ooooo Factory F: Unmodified sequence antisense strand sequence (5'-3·) ΓUCAGUCAUAUCCUCGAACA | ACUGCGGUUGUACAGUGAA | UCUUUUGUCAACGAAGAGA | GAGGGUAGACAUUUAUACUA | UGAGGCAAGAGUCUUGUGA | UCAGGUAUAAAGUAAAGCG | UGUAUAUUAUCAGUCGUGU | UCGAACACAGGCUGUCUUU j | AUUAUUACUGCUCUACAG | AAAGCGUGUUGUCAAUAAA | | CUCGGGUAUUCUGUUAUGG | | AUAAACAUCAUUUCCUUGA | | UGCGGUUGUACAGUGAAGU | | UAUUCCGUAUUACUGCGGU | | AAGAAUAUGAGAUCACUUU | | UUGAAAGCAUCAUCUUCCU | | UUUGAGGCGGCUUUCUUUG | | GUGUUGUCAAUAAACAUCA | | AAGUUAGUGAGAGUGAACA | | GAGGCGGCUUUCUUUGUCC | | UUCCGUAUUACUGCGGUUG | | GGUUUGAGGCGGCUUUCUU | | UUCUGAAAGAAUAUGAGAU | | GCCUCGGGUAUUCUGUUAU |! CAUAUCCUCGAACACAGGC | UAAAGCGUGUUGUCAAUAA | GAUGUAAGUUAGUGAGAGU | UACUCUAUAAAUCAUGCAG | AUAUUCCGUAUUACUGCGG | GUCAUCACAAGGCGCAUGU | C GGGUAUUCUGUUAUGGAA | AUAUGAGAUCACUUUGUAU | UUGACGCAAGAGUCUUCUG | GCUAAUCAUCUUUCUGGAA | SEQ ID NO o (N | 522 | 524 OO &lt;N | 532 Ό 00 〇1 544 | 1 546 1 丨548 | 1 550 | 1 552 1 1 554 1 1 556 | 00 o 'sO \r\ 1 562 1 s Vi 566 | 00 V) ! 570 | 572 | 00 o 00 582 | s VO 00 stock sequence (5'-3') | UGUUCGAGGAUAUGACUGA ΓUUCACUGUACAACCGCAGU | UCUCUUCGUUGACAAAAGA | UAGUAAAAUGUCUACCCUC | UCAGAAGACUCUUGCGUCA [CGCUUUACUUUAUACCUGA | ACCAGACUGAUAAUAUACA | AAAGACAGCCUGUGUUCGA ICUGUGAAGGAUAGUAAAAU | UUUAUUGACAACACGCUUU | CCAUAACAGAAUACCCGAG | UCAAGGAAAUGAUGUUUAU | | ACUUCACUGUACAACCGCA | | ACCGCAGUAAUACGGAAUA | | AAAGUGAUCUCAUAUUCUU | | AGGAAGAUGAUGCUUUCAA | | CAAAGAAAGCCGCCUCAAA | | UGAUGUUUAUUGACAACAC | I UGUUCACUCUCACUAACUU |! GGACAAAGAAAGCCGCCUC | CAACCGCAGUAAUACGGAA | AAGAAAGCCGCCUCAAACC | AUCUCAUAUUCUUUCAGAA | AUAACAGAAUACCCGAGGC | GCCUGUGUUCGAGGAUAUG | UUAUUGACAACACGCUUUA | ACUCUCACUAACUUACAUC | CUGCAUGAUUUAUAGAGUA | CCGCAGUAAUACGGAAUAU | ACAUGCGCCUUGUGAUGAC | UUCCAUAACAGAAUACCCG AUACAAAGUGAUCUCAUAU | CAGAAGACUCUUGCGUCAA | UUCCAGAAAGAUGAUUAGC | SEQ ID NO | 519 | 523 (N 1 529 m 1 533 ♦n 1 537 | Os 1 545 | 1 547 | 丨549 1 »r&gt; 1 553 | Γ55Τ1 丨557 1 1 559 | 565 | 1 567 | 1 569 | 丨573 | 1 575 1 I 577 | L579I 00 m 00 00 152219.doc -87- 201130494 Modified sequence antisense strand sequence (5'-3') 1 UUGAUcAAuAUcAGUcAuATsT | I CUCuAuAAAUcAUGcAGCCTsT II GGUUGuAcAGUGAAGUCGGTsT II AGGGuAGAcAUUUuACuAUTsT II CUUUGAUcAAuAUcAGUcATsT I 1 cAGGCGAGGUcAUcAcAAGTsT II AuAUcAGUcAuAUCCUCGATsT II AAAuAcAGGCGAGGUcAUCTsT II AAAuAAACGUGUUuACUCUTsT I 1 ACuAUCCUUcAcAGAGAGGTsT | 1 UGUUGUcAAuAAAcAUcAUTsT | I AAGUCGGCcAAAGUUGUCUTsT I UCGGGuAUUCUGUuAUGGATsT I CGuAUuACUGCGGUUGuACTsT I 1 GGCGcAUGUGUGCuAAUcATsT | 1 GCGcAUGUGUGCuAAUcAUTsT I 1 UUcAGGuAuAAAGuAAAGCTsT | 1 UuACUCuAuAAAUcAUGcATsT | 1 AcAGUGAAGUCGGCcAAAGTsT | I UcAAuAUUUUcAGGUGGAUTsT I 1 AGUGAGAGUGAAcAUuAcATsT | 1 UcAUcAAuAUUUUcAGGUGTsT | 1 GCGGUUGuAcAGUGAAGUCTsT | 1 AGCCUCGGGuAUUCUGUuATsT | 1 cAcAGCcAGUCCUCUuA CUTsT | 1 AUUCCGuAUuACUGCGGUUTsT | 1 UuAcAGGAGAGGGuAGAcATsT | 1 GAAGUCGGCcAAAGUUGUCTsT | 1 cAUGcAGCCUCGGGuAUUCTsT | 1 ACCuAACUUUGAUGuAAGUTsT | 1 AGGCGcAUGUGUGCuAAUCTsT | CcACCuAACUUUGAUGuAATsT | SEQ ID NO 1 720 II 722 1 1 724 II 728 1 1 730 I 1 732 I 1 734 1 VO § Bu Bu thousand and 1 742 1 748 1 750 I 1 752 I 754 1 756 I 1 758 760 s 1 764 1 1 770 1 1 772 1 774 1 778 Sense strand sequence (5'-3'&gt; 1 uAuGAcuGAuAuuGAucAATsT | I GGcuGcAuGAuuuAuAGAGTsT II ccGAcuucAcuGuAcAAccTsT I AuAGuAAAAuGucuAcccuTsT II uGAcuGAuAuuGAucAAAGTsT II cuuGuGAuGAccucGccuGTsT I 1 ucGAGGAuAuGAcuGAuAuTsT I 1 GAuGAccucGccuGuAuuuTsT I | AGAGuAAAcAcGuuuAuuuTsT | | ccucucuGuGAAGGAuAGuTsT | 1 AuGAuGuuuAuuGAcAAcATsT | I AGAcAAcuuuGGccGAcuuTsT I uccAuAAcAGAAuAcccGATsT | GuAcAAccGcAGuAAuAcGTsT | 1 uGAuuAGcAcAcAuGcGccTsT | 1 AuGAuuAGcAcAcAuGcGcTsT I 1 GcuuuAcuuuAuAccuGAATsT I uGcAuGAuuuAuAGAGuAATsT | 1 cuuuGGccGAcuucAcuGuTsT I 1 AuccAccuGAAAAuAuuGATsT | 1 uGuAAuGuucAcucucAcuTsT | 1 cAccuGAAAAuAuuGAuGATsT | 1 GAcuuc AcuGuAcAAccGcTsT | | uAAcAGAAuAcccGAGGcuTsT | | AGuAAGAGGAcuGGcuGuGTsT | 1 AAccGcAGuAAuAcGGAAuTsT | 1 uGucuAcccucuccuGuAATsT | 1 GAcAAcuuuGGccGAcuucTsT | | GAAuAcccGAGGcuGcAuGTsT | 1 AcuuAcAucAAAGuuAGGuTsT | | GAuuAGcAcAcAuGcGccuTsT | uuAcAucAAAGuuAGGuGGTsT SEQ ID NO 1 719 1 721 723 (N 1 727 1 729 P 1 733 1 Bu 1 737 1 ON P m 1 745 1 1 747 1 1 749 1 jn ΓΟ jn —757 1 759 1 3 1 769,1 P 1 775 1 1 777 1 On 〇〇Unmodified sequence antisense strand sequence (5'-3·) 1 UUGAUCAAUAUCAGUCAUA | [CUCUAUAAAUCAUGCAGCC | 1 GGUUGUACAGUGAAGUCGG | 1 AGGGUAGACAUUUUACUAU | 1 CUUUGAUCAAUAUCAGUCA | 1 CAGGCGAGGUCAUCACAAG | 1 AUAUCAGUCAUAUCCUCGA | 1 AAAUACAGGCGAGGUCAUC | | AAAUAAACGUGUUUACUCU | 1 ACUAUCCUUCACAGAGAGG | 1 UGUUGUCAAUAAACAUCAU | DUDCDD a 1 uuaau D a UCGGGUAUUCUGUUAUGGA 1 CGUAUUACUGCGGUUGUAC | 1 GGCGCAUGUGUGCUAAUCA | 1 GCGCAUGUGUGCUAAUCAU | 1 UUCAGGUAUAAAGUAAAGC 1 UUACUCUAUAAAUCAUGCA | 1 ACAGUGAAGUCGGCCAAAG | 1 UCAAUAUUUUCAGGUGGAU | 1 AGUGAGAGUGAACAUUACA | 1 UCAUCAAUAUUUUCAGGUG | 1 GCCGUUGUACAGUGAAGUC | 1 AGCCUCCCGUUCUCCUUAUA | | CACAGCCAGUCCUCUUACU | 1 AUUCCGUAUUACUGCGGUU | 1 UUACAGGAGAGGGUAGACA | 1 GAAGUCGGCCAAAGUUGUC | 1 CAUGCAGCCUCGGGUAUUC | 1 ACCUAACUUUGAUGUAAGU | 1 AGGCGCAUGUGUGCUAAUC | CCACCUAACUUUGAUGUAA SEQ ID NO 1 588 1 1 590 1 (N Os ON VO ON yri 1 598 1 1 600 1 1 602 1 1 606 1 1 608 1 〇&lt;N 5 VO s 1 618 1 1 &lt;N &lt;N v〇3 丨626 | 1 628 1 1 630 1 &lt;N cn v〇丨634 | 1 636 1 〇 〇mv〇1 640 1 (N s 1 648 1 0 Ό SO stock sequence (5'-3') 1 UAUGACUGAUAUUGAUCAA | 1 GGCUGCAUGAUUUAUAGAG | 1 CCGACUUCACUGUACAACC | 1 AUAGUAAAAUGUCUACCCU | 1 UGACUGAUAUUGAUCAAAG | 1 CUUGUGAUGACCUCGCCUG | 1 UCGAGGAUAUGACUGAUAU | 1 GAUGACCUUCUGCUAUUU | 1 AGAGUAAACACGUUUAUUU | 1 CCUCUCUGUGAAGGAUAGU | 1 AUGAUGUUUAUUGACAACA | 1 AGACAACUUUGGCCGACUU | UCCAUAACAGAAUACCCGA | GUACAACCGCAGUAAUACG | 1 UGAUUAGCACACAUGCGCC | 1 AUGAUUAGCACACAUGCGC | 1 GCUUUACUUUAUACCUGAA | 1 UGCAUGAUUUAUAGAGUAA | 1 CUUUGGCCGACUUCACUGU | | AUCCACCUGAAAAUAUUGA | 1 UGUAAUGUUCACUCUCACU | 1 CACCUGAAAAUAUUGAUGA | 1 GACUUCACUGUACAACCGC | | UAACAGAAUACCCGAGGCU | 1 AGUAAGAGGACUGGCUGUG | 1 AACCGCAGUAAUACGGAAU | 1 UGUCUACCCUCUCCUGUAA | 1 GACAACUUUGGCCGACUUC | 1 GAAUACCCGAGGCUGCAUG | 1 ACUUACAUCAAAGUUAGGU | 1 GAUUAGCACACAUGCGCCU | UUACAUCAAAGUUAGGUGG SEQ ID NO Shu 587,115,891 square \ Os Os Os * 0 ss V〇 1 607 1 1 609 1 v〇VO Bu v〇Os s 1 623 1 1 625 1 Bu (N 1 629 1 sm 1 635 1 I 637 1 1 639 1 i 5 VO 1 645 | P- s 〇\ ·88· 152219.doc 201130494

dsRNA SEQ ID 255/256 selected off-target human interleukin 18 (interferon gamma-inducing factor) (IL18), mRNA human mannosidase a, species 2A, member 1 (MAN2A1), mRNA human vacuoles Sorting protein 24 homolog (S. cerevisiae) (VPS24), transcript variant 1, mRNA human vacuolar sorting protein 26 homolog B (S. pombe) (VPS26B) , mRNA Human guanine nucleotide binding protein (G protein) yl3 (GNG13), mRNA human ankyrin repeat containing 2 and LEM domain (ANKLE2), mRNA human HBS1-like (Saccharomyces cerevisiae) (HBS1L), transcript variant 1, mRNA Human kinesin family member Cl (KIFCl), mRNA prediction: human hypothesis LOCI00290412 (LOC 100290412), miscRNA human solute carrier family 35, member C2 (SLC35C2), transcript variant 1, mRNA &lt; 1 δ 潦Η Τ3 cC 3 ¥ 凛m &lt; Human TSPY-like 4 (TSPYL4), mRNA Human leucine-rich repeat of 16A (LRRC16A), mRNA Human Rho guanine nucleotide exchange factor (GEF) 5 (ARHGEF5) , mRNA contains the human retrotransposon gag domain (RGAG4), mRNA accession number ΝΜ_001562.2 NM—002372.2 ΝΜ_016079. 2 NM—052875.3 NM 016541.2 — ....___1 NM_015114_1 NM_006620.3 NM—002263.3 XR—079415.1 NM_173179.2 NM_020127.2 NM_021648.4 ΝΜ_017640.4 NM_005435.3 NM_001024455.2 Antisense Target Antisense Target 1 Antisense Off-target 2 antisense target 3 antisense target 4 antisense target 5 antisense target 6 antisense target 7 antisense target 8 antisense target 9 antisense target 10 antisense target 11 antisense target 12 sense off target 13 sense off target 14 152219.doc •89- 201130494 dsRNA SEQ ID 239/240 selected off-target human interleukin 18 (interferon gamma-inducible factor) (IL18), mRNA human GTP-binding protein 2 (GTPBP2), mRNA human AHNAK nucleoprotein 2 ( ΛΗΝΑΚ2) , mRNA Human serologically defined colon cancer antigen 3 (SDCCAG3), transcript variant 1, mRNA prediction: human putative protein LOC100288296 (LOC100288296), mRNA human olfactory receptor, family 51, subfamily I, member 2 (OR51I2 ), mRNA contains 5A human hemophilic factor A domain (VWA5A), transcript variant 1, mRNA human alpha kinase 1 (ALPK1), transcript variant 1, mRNA human 10 from 0100 (10^0100), 1111^ Eight human collagen, type XXVIII, al (COL28Al), mRNA Triad-like peptide repeat domain 14 (TTC14), transcript variant 1, mRNA 12 human thioredoxin domain (endoplasmic reticulum) (TXNDC12), mRNA human zer-Ι homolog (C. elegans )) (ZERl), mRNA human capsid protein IV (CPNE4), mRNA human CD109 molecule (CD109), transcript variant 1, mRNA accession number NM_001562.2 NM_019096.3 NM-138420.2 ΝΜ_001039707.1 XM_ 002343072.1 NM_001004754.1 ΝΜ_014622 .4 NM_025144.3 ΝΜ_014680.2 NM_ 001037763.2 NM_133462.3 NM_015913.2 NM—006336.2 NM_130808.1 NM_133493.3 Antisense Target Antisense Target 1 Antisense Target 2 Antisense Target 3 Antisense Target 4 Antisense Target 5义 off target 6 antisense off target 7 antisense off target 8 antisense off target 9 antisense off target 10 antisense off target 11 antisense off target 12 sense off target 13 sense off target 14 -90- 152219.doc 201130494

dsRNASEQ ID 165/166 selected off-target human interleukin 18 (interferon gamma-inducing factor) (IL18), mRNA, human retinol-binding protein 1, cell (RBP1), transcript variant 1, mRNA, human SET containing 4 Domain (SETD4), Transcriptional Variant 1, mRNA Human Transmembrane Protein 41A (TMEM41A), mRNA BRCA1 Gene 1 Human Adjacent Protein (NBR1), Transcriptional Variant 1, mRNA Human Zinc Finger Protein 697 (ZNF697), mRNA Human Single-induced proliferation-associated 2 (SIPA1L2), mRNA human Golgi-localized protein (GOLSYN), transcript variant 1, mRNA human pear-shaped stone (Drosophila) (BOLL), transcription Variant 1, mRNA Human solute carrier family 30 (zinc transporter), member 8 (SLC30A8), mRNA Human gamma aminobutyric acid (GABA) A receptor, s (GABRE), mRNA Human DnaJ (Hsp40) homolog , subfamily C, member 6 (DNAJC6), mRNA containing human pleckstrin homology domain, family A (phosphoinositide binding specificity) member 3 (PLEKHA3), mRNA human retinoblastoma binding Protein 4 (RBBP4), transcriptional variant 1, mRNA, human centromere protein E, 312kDa (CENPE), mRNA accession number ΝΜ_00 1562.2 NM—002899.3 ΝΜ_017438.2 NM_080652.3 NM_005899.3 ΝΜ 001080470.1 NM_020808.3 ΝΜ_001099744.1 NM_197970.2 NM—l 73851.2 NM_004961.3 NM_014787.2 ΝΜ_019091.3 NM_005610.2 NM_001813.2 Antisense target antisense target 1 antisense target 2 1 antisense target 3 antisense target 4 antisense target 5 antisense target 6 antisense target 7 antisense target 8 antisense target 9 antisense target 10 antisense target 11 antisense off target 12 sense off target 13 sense off target 14 152219.doc • 91 201130494 π &lt; antisense shares sequence (5'-3 ') GCCUGCGGCAAAGUGUUUCdTdT GCCUGCGCCAAAUUAUUUCdTdT CCCUGCGGUAAAUAGUCUGdTdT UCCUGCCACAAAGAGUUUCdTdT ACCUGUGACAAAAAGUUUCdTdT GCCUGCAACAAAUUGCUUUdTdT UCCUGUGACAAAUUCUUUAdTdT UCCUGCAACAAGUAGAUUAdTdT UCCUGCAACCAAUGGUUUUdTdT CCCUGCCACACUUAGUUUCdTdT GCCAGCGCCAAAUACUUUGdTdT UUCUGCGUCAAAUAGUAUGdTdT UAAACUAUUUGUUUUAGGAdTdT | AAAACUAGUUGUUACAGGAdTdT CGGCUAUCUUUUUAUAUUUdTdT UGGCUAUCUUUAUUAAAAGdTdT UGGCUAUCUUCUUCCAUAUdTdT GGGCUAUCUUAAGAAAUAUdTdT UGGCUAUCUUGUUACAUGAdTdT AGGCUAUCAUAAUAUAUAUdTdT GGGCUAUGUUUCUAAAUACdTdT AGUCUAUCUUUAUGCAUAUd TdT GUGCUAUCUUUUUACAUAUdTdT AGGUUAUCUUAAUACAUAAdTdT UGGCCAUCCUUAUACAUACdTdT UGUCUCUCUUUAUACAUAUdTdT UUAAGUAUAAAAAUAGCCUdTdT UUGUGUAUAGAGAUAGCCUdTdT UUUAUUAUCAUGUCAUUUGdTdT SEQ ID NO oo in 00 〇VO OO CN v〇oo OO OO 00 VO 00 870 872 874 876 OO oo 880 882 &lt; 50 VO 00 00 00 00 oo 890 892 894 VO On 00 00 〇00 900,902,904,906,908 〇912 914 shares a sense sequence (5'-3 ·) GAAACACUUUGCCGCAGGCdTdT GAAAUAAUUUGGCGCAGGCdTdT CAGACUAUUUACCGCAGGGdTdT GAAACUCUUUGUGGCAGGAdTdT GAAACUUUUUGUCACAGGUdTdT AAAGCAAUUUGUUGCAGGCdTdT UAAAGAAUUUGUCACAGGAdTdT UAAUCUACUUGUUGCAGGAdTdT AAAACCAUUGGUUGCAGGAdTdT GAAACUAAGUGUGGCAGGGdTdT CAAAGUAUUUGGCGCUGGCdTdT CAUACUAUUUGACGCAGAAdTdT UCCUAAAACAAAUAGUUUAdTdT UCCUGUAACAACUAGUUUUdTdT AAAUAUAAAAAGAUAGCCGdTdT CUUUUAAUAAAGAUAGCCAdTdT AUAUGGAAGAAGAUAGCCAdTdT AUAUUUCUUAAGAUAGCCCdTdT UCAUGUAACAAGAUAGCCAdTdT AUAUAUAUUAUGAUAGCCUdTdT GUAUUUAGAAACAUAGCCCdTdT AUAUGCAUAAAGAUAGACUdTdT AUAUGUAAAAAGAUAGCACdTdT UUAUGUAUUAAGAUAACCUdTdT GUAUGUAUAAGGAUGGCCAdTdT AUAUGUAUAAAGAGAGACAdTdT AGG CUAUUUUUAUACUUAAdTdT AGGCUAUCUCUAUACACAAdTdT CAAAUGACAUGAUAAUAAAdTdT SEQ ID NO 00 OS 00 CO VO oo OO OO 869 yr) 879 OO OO 00 00 vn oo 00 00 ON 00 00 1—^ ON 00 00 On 00 1 ON a\ 00 s ON s On ON OS 5: 152219.doc ·92· 201130494 Η ΐ 〇Η Τ ϋ ϋ ϋ & & & α lt &lt;&lt; lt Ρ Ρ & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & Ρ 口 口 口 mouth mouth &mouth; o ϋ ο ϋ ο ο ο ο ϋ 5 口ο Ρ Ρ ρ Ρ Ρ 〇ο &lt; υ &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; ρ ρ υ υ υ &lt; υ υ υ υ ο ο &lt;&lt; Μ Ρ &lt; υ Ρ ρ D υ υ c &lt;&lt;&lt;&lt; υ &lt; &&lt;&lt;&lt;&lt; ο Ρ Ρ mouth &lt; ρ Ο Ρ ο ρ 口Ρ ο 〇ο &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; ρ &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&gt;&gt; υ α P 5 ρ υ υ υ D υ U υ υ υ υ &lt; Ο &lt; ο &lt; υ &lt; Ο z Q n VO 00 α\ ΟΝ 〇\ 艺Ον ΟΝ 00 ο m Ον (Ν Os ν〇 m Os 00 ο &lt; Η &quot;Ο Η Τ3 Η Τ3 Η Τ3 Η -3⁄4 Η ό ο ϋ ϋ &lt; ϋ &lt;! υ Ρ &lt; υ Ο &lt;&lt;&lt; & ζ Ο ϋ ο &lt;&lt; ο Ο &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; υ ο υ ih &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; υ &lt; υ υ &lt; Ο D ρ &lt;&lt;&lt;&lt; Ο &lt;&lt;&lt;&lt;&lt; Ο ο Domain: 〇 ο ο ο ϋ ο ο ϋ ρ ο ο ρ mouth; D ϋ Ρ Ρ &lt; C &lt;&lt; υ &lt; c &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; υ υ U υ &lt; υ ο υ υ υ υ υ U &lt; 杷u &lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt; ϋ &lt; ο o ο ο ο ϋ ϋ ο ο ϋ 口 &lt; D ο &lt; ϋ ο ο ο ϋ ο ϋ u &lt;&lt;&lt;&lt; &Lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;&lt;; ο ο 口 &lt; υ o Q ΟΝ ΟΝ &lt;^ 5: m ΟΝ ΟΝ σ\ m ΓΛ ΟΝ 5: Ρ: ΟΝ 〇\ m ΟΝ Ifl -93 152219.doc 201130494 291^ 甽 _ _ s s goose 00 00 Oo cs v〇ON Ο OO ro 00 00 5 芝 I ^ί% m CN 04 oo On so oo ON C\ 00 VO oo oo 00 Ο ΟΝ suitable isl) CO QU CDS 00 QU 00 QU 00 QU 00 Q 〇00 QU 00 QU | 3UTR 1 3UTR 1 3UTR 3UTR 1 oo Q 〇CDS 1 1 CDS 1 rn BH •®宝1 9 10 18 8 14 17 89 11 19 1 89 10 19 ON rH fH m rH 69 19 5 15 16 19 1 6 。 ON ON ON 丨 丨 ON ON .oo | 1 11.25 ! 12.00 | 12.20 | | 12.20 1 | 12.25 j 1 12.25 1 20.00 11.00 11.00 WnS · According to 5^ TGACCAAGGAAATCGGCCT TCACCAAGGGCATCGGCCA TGCCCGAGGAAGTCGGCCT AGACCAAGAACCTCGGCC T AGACCAAGGGCCTCGGCCG AGACAAAGGAAATCCGCCG AGACCAAGGACATGGGCCT AGAGGAAGGAAATCAGCCT AGACCCAGGGAATGGGCCC TGAGCAAGTAAATTGGCCT ACACCAAGGATATCGGCAC CTACCAAGGATATCAGCCT AGACCAAGGAAATGGCCCG AGGCCGACTTCCTTGGTGG AGGCCTATTTCCTTGGTAG accession number NM 001562.2 NM 019096.3 NM 138420.2 NM 001039707.1 XM 002343072.1 NM 001004754.1 NM 014622.4 NM 025144.3 NM 014680.2 NM 001037763.2 NM 133462.3 NM 015913.2 NM 006336.2 ΝΜ 130808.1 NM 133493.3 dsRNA Seq ID 255/256 Antisense target antisense target 1 antisense target 2 antisense target 3 antisense target 4 antisense target 5 antisense target 6 antisense target 7 antisense target 8 antisense target 9 antisense target 10 antisense target 11 antisense Off-target 12 antisense off target 13 antisense off target 14

152219.doc -94- 201130494

(q 9I&lt;Hot sm yn H 00 〇\ Ο ί-Η 00 (N VO 〇 inch fSi § w * 1 sg 73 2 pen v〇(N Ο Os 00 ON s &lt;N as CTN as οο Ο s ON 00 00 〇\ 嗵lEll 00 QU 3UTR | 3UTR | 3UTR | 3UTR QU 3UTR ζΛ Q υ QU 3UTR 3UTR 3UTR 00 〇a 00 QU 3UTR in ^ ^ ^ im OH 12 15 16 19 11 13 15 1 ON Ό 00 00 1-H Inch yn 1 2 12 19 1 2 16 19 1 6 16 19 7 15 19 (N yn Ον inch CN 1 2 10 19 ON VO 〇\ m rH an o inch m CN CN inch inch m inch inch m inch 1 specific score _ioo Ο rn ro cn 11.00 li.oo | 11.00 11.00 11.00 11.00 11.00 11.00 11.20 Η έΙ ft ACTCTCTCCTGTGAGAACA TCTGGCTACTGTGAGAACA ACTCCCACTTGTGAGAACA CCTTTCTTCTGGGAGAACT ACTCTATCCTGTGAGACCA ACTGTCTCCTGTGAAAACA CCTCTCTACTGTGAGAAAT CCTGTCTCCTGTGAGAAAG CCTTTCTCCTGTGTGAACT TCTCGCTCCTGTTAGAACA TCTCTCTGCTGTGAAAACT TCTCTGTCCTGTGAGAAGC CCTCTCTCCAGTGAGAATC GGTTCTCACAGGACAGAGC AGTTCTGAGAGGAGAGAGG accession number NM 001562.2 NM 002372.2 NM 016079.2 NM 052875.3 NM 016541.2 NM 015114.1 NM 006620.3 ΝΜ 002263.3 XR 079415.1 NM 173179.2 NM 0 20127.2 NM 021648.4 NM 017640.4 NM 005435.3 NM 001024455.2 ζΛ Μ &lt; as *y 2 ^ is antisense target antisense target 1 antisense target 2 antisense target 3 antisense target 4 antisense target 5 antisense target 6 antisense off target 7 antisense off target 8 antisense off target 9 antisense off target 10 antisense off target 11 antisense off target 12 antisense off target 13 antisense off target 14 152219.doc -95- 201130494 (o9I&lt; CN 〇 〇 \ ON (N inch m 卜卜Vn Ο f Si δ « ^ CN oo ON Os OO cn ON 00 00 VO &lt;N v〇s I2i) 1 CDS | 1 3UTR 1 1 3UTR 1 1 3UTR 1 3UTR | 3UTR | CDS | 3UTR 1 3UTR 3UTR 1 3UTR 3UTR I CDS I 3UTR I 1 CDS un ira ΌΠ rn 1 13 14 17 00 CN On 00 OO Q\ m 00 Q\ CN 00 ON Bu 128 00 m cn 3 17 18 2 13 17 1 28 12 m CN 1 12 13 18 19 9 17 18 {θ ππ o inch inch yn inch m cn inch m &lt;nm specific score oo Ο cn ΓΟ CO o cn 〇rn I li.oo ! | 11.50 | | 12.00 I 12.00 | 12.00 1 12.50 20.00 〇CO (N Rn Target/Off-target site [Sense, 5'-3'] TGTTCACTGTTCAAAACGA TGATCTGTGTTCAAAACGT TTTTCACCTTTCAAAACGG ATTTCATTGTTTAAAACGT CGTTCATTATTTAAAACGT GGTTCACC CTTGAAAACGT AGCTCACTGTTCAAAAAGT TGTTCACTGTTTAAAACCG CATTCATTGTTCAAAAGGT TAATCACTGTTCAAAAGGA TGCTCAGTGTTCAAAACCA TGTTCACAGTTTAAAACAT TGTTCACTGTTCAAAAAAT AAGTTTATAACAGTGAACT TTATTTTGAAAAGTGAACA accession number NM 001562.2 NM 002899.3 NM 017438.2 NM 080652.3 NM 005899.3 NM 001080470.1 NM 020808.3 NM 001099744.1 NM 197970.2 NM 173851.2 NM 004961.3 NM 014787.2 NM 019091.3 NM 005610.2 NM 001813.2 dsRNA Seq ID 165/166 antisense Target antisense target 1 antisense target 2 antisense target 3 antisense target 4 antisense target 5 antisense target 6 antisense target 7 antisense target 8 antisense target 9 antisense target 10 antisense target 11 antisense target 12 Antisense off target 13 antisense off target 14

152219.doc -96- 201130494

% Μ ti W average maximum inhibition [%] 〇〇〇〇m/A average IC80 [ηΜ] 2.3108 m/A Delete A -δ- Μ — &lt; average IC50 [ηΜ] 0.0235 m/A m/A Average IC20 [ ΜΜ] 0.0004 #N/A m/A Host No. 00 001562.2 NM 019096.3 NM 025144.3 255/256 Antisense Target Antisense Target 1 Antisense Target 7 Μ Si φή Average Maximum Suppression [%] CN m/A Average IC80 [ηΜ ] 4.3625 m/A m/A m/A 43⁄4 &lt; Average IC50 [nM] 0.3339 m/A m/A m/A Average IC20 [nM] 0.0275 11.5950 m/A m/A Registration number NM 001562.2 NM 019096.3 NM 025144.3 NM 130808.1 239/240 Antisense target 1 antisense target 7 antisense target 13 w 鹚φ4 i? 溆 average maximum inhibition [%1 #Ν/Α m/A average IC80 [ηΜ] 0.4388 #Ν/Α m/A m/A -6- Μ &lt; average IC50 [nMJ 0.0012 #Ν/Α m/A 18.2843 Average IC20 [ηΜ] 0.0000 #Ν/Α m/A 0.2750 Registration number 00 001562.2 ΝΜ 138420.2 NM 025144.3 NM 006336.2 165 /166 Antisense target 2 antisense off target 2 antisense off target 12 152219.doc -97- 201130494 8I&lt; SEQ ID No 942 On 944 JO o OnOn On 948 949 950 as 952 m 954 955 VO 〇\ 957〇〇\ 959 960 s Os 962 m 964 965 966 967 00 VO ON Ώ) cd 00 total cd S) ωι cd S) ϋύ ϋύ a cd bO g) cO oo Ώ) CO through ϋ from W) s 8 §S cd To cd S Οβ 1 磬ui O ϋ ω) s 0 tb 1 8 〇tb 1 s S) W) oe HH 芘OD Ώ) DO S 芘ο to 1 or) I 蓉 o From S: gg λ ω) S) bO 笤cd &amp; CiO 芘cd 0Λ 1 | is 0 1 ω na cd ω ο _ Η ω ω ω to Ci〇1 ο §8 S) &amp; a 8 cd 〇ΰ 5) ωι 1 E 0JD U Λ S) Σ3 S) Si i 8 cd S) 5 too E oa U) 6 Pan 8 W) 1 S) e O δ Si s Forgo S) S) i W) cd ab〇g) § W) g) υ ω) S ω is 芘s S) S) wear cd §S &amp; % i BS) s (DX) H &amp; B Daddy S) S) s &amp; CiO 芘0 ΰ〇λ cd Total Λ op Η Η 1 GJO Λ b0 苕ω) W) &amp; g) i 8 cd DO E g S o to cd wear S) W) o 〇0 Λ Λ cd 萏cd 笤Η Η ο ο dad ο cd ο nuο Λ ω) S) 1 Ο Λ S) ω) Ε total δ tb I 4—· υ ω) 〇 c〇S 〇〇 — I3 μ 〇S ig) S) 0D W) OX) Solanum DO ti Ώ) tb s S) 1 i 00 f OX) i 8 cd b〇E tsfi tb if 8 S) 13 8 〇Si ω cd 萏ao gs s S) ss 5 t! g W) § E Η ti 00 tb Ϊ 8 2 O g) M s S) 苕S: (b) W) bp 8 S) 8 i 8 cd S) § &amp;β EH 1 Nu SS &quot;S &amp; W) Wear cd 萏8 S) Sb S3 Pan O o Dad ω) Function OQ DQ S UJ 〇ω ο SS PQ U soss S ss -I ω -1 W *) S ω ω η4 S ss PQ ss ω hj FPL name off target-1 hGTPBP216 hGTPBP221 hGTPBP23 hGTPBP24 hGTPBP213 hGTPBP217 hGTPBP218 hGTPBP222 hGTPBP225 hGTPBP228 hGTPBP21 hGTPBP22 hGTPBP25 hGTPBP26 hGTPBP27 hGTPBP28 hGTPBP29 hGTPBP210 hGTPBP211 hGTPBP212 hGTPBP214 hGTPBP215 hGTPBP219 hGTPBP220 hGTPBP223 hGTPBP224 hGTPBP226 hGTPBP227 152219.doc -98- 201130494

6I&lt; SEQ ID No a\ V〇ON o ON r—^ Os CN ON cn ON inch ΐ 976 977 978 979 980 00 ON 982 m 00 984 00 Os 986 987 00 00 ON On 990 ON 992 〇\ §: v〇 On a\ sequence ooaoo to DO C cd 萏I OJ) ubiquitous S) ί§ ω as 〇H C3 Ώ) Λ SSW) W) another tb a λ «s OJQ cd Λ DJO _g) o § HH o So Λ S Dad ω) λ cd σ3 tb σ3 bC CJO tb cd s W) Λ 00 ω) ο Moss Η g) § ο &amp; 〇β bO to t: i 〇Η Ε tb cd S) ο a λ ω) ο Ωι &amp;〇λ cd cd 00 cd cd cd DO CU) Labor H 00 c3 00 o 0 1 b〇cd CO b0 a &amp; square ο cd Ώ) 5 S) § Sd 〇H i 6 GO &amp; 00 〇 Λ bO ο ο cd 00 cd ο cd t5 ω) υ td bJ) dad ο 1 ω) cd cd Η Η Η amp &amp; cd ο ο 笤 &amp; cd 00 cd cd ο cd cd υ ο Si cd S) H卜[: aa U) S1 〇e cd 运 ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ό ) ) ) ) ό ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ^dC 〇 Η Η η ο ο GO ω ω 3 3 3 3 3 3 3 3 3 3 cd cd cd cd cd cd cd cd cd cd υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ υ s OD s -4-&gt; ooso S & cd (Λ tuo g HHHS) 8 MS) ccctcagggacgccagtaacTTTTTgaagttaccgtttt goods W) λ λ 诖cd Ci〇wu HHH όβ Λ GO do 芘ω) 00 negative OX) ω) a 00 8 ο i ο Λ S) DO &amp; Λ 芘 ss S5 δ o 萏b〇S cd 萏 3) s HH 8 parts S 8 ωι S) 萏 column T3 W) § wear GO HHH [: S) bfi H 〇〇 β cd bfl bO ob labor 03 U) ss DO S) HHW) W) Οΰ S) op dfl 1 gg) Λ S) § toO _ 芘S) W) W) 菱 o OX) a Λ cd u Λ HP HH λ g) cd 0 Ήΰ Λ W) 〇1 bO Λ cd i OS) § bO S) 〇W) o S o OX) Λ Λ cd o 芘a top Giant H o bi) bil cd o U) cd Other &amp; υ e cd o Function μ-J 0Q μ-1 m ω u W Ο WU ω υ ω υ mu ω υ ω U ω hj ω ω ω W hJ ω ω hJ w hJ S ω S s ω hj ω vl S PQ S ω FPL name ALPK14 ALPK127 ALPKll ALPK15 ALPK110 ALPK115 ALPKll 8 ALPK121 ALPK124 ALPK128 ALPK12 ALPK13 ALPK16 ALPK17 ALPK18 ALPK19 ALPK111 ALPK112 ALPK113 ALPK114 ALPK116 ALPKll 7 ALPK119 ALPK120 ALPK122 ALPK123 ALPK125 ALPK126 152219.doc -99- 201130494 0(N&lt; SEQ ID No ON ON OO On ON C\ oo * | 1 〇S 〇S ο Ο 〇〇O os OO o Ο (N 〇Γ&lt;Ί inchΟ m iH Ό Ο ο 00 o 1—Η ?—Η oo 〇Λ I sb〇1 cd 芘Λ ο i •4-» υ &0 &amp;0 Λ &amp; 00 Tb S) a S) as S) cd ο δ sj ω) b〇e bb cd ϋ 1 ί5 S ω) S) ω 1 ω ω SS SS) tb Λ s CD 1 Μ ο 8 dD a &quot;cd * -* 'aa bJO W) 0 § cd 1 ω) ο S Η bb 1 U) S) ωι § S3 I ts §§ S s〇Λ 〇S) SW) α 运 1 tb SS) cd ο So i tb S) e 8 S o W) i 8 cd i) § OX) 芘ss 萏I o ; ω) cd 3) g E CH 芘S) be 0 1 io t5 i 0 g» W) cd Sb cd 1 8 Λ to ω C^ total S) H bp dad S) — 1 5 1 8 cd 00 to 00 〇Μ § 3 tb S) Ϊ W) ω Ο So ω) 1 00 目 &amp; 〇 00 rt ο ϋ Λ ωι ο goods 1 萏S) 1 ϋ Sj dad s 1 cd ; b〇i O ao E ω) § S) 0β S ο ω 芘 )S) s cd 萏Si λ t3 •|-* 5 cd 洤S) i 8 Λ OJO to ο with Ofl §s ϊ ωSpecial 芘W) CQ S) Η ES) I 1 Si δ 00 i ο Λ to _ §S cd tb 1 bfl 13 00 ¢0 WJ wear cd even W) cd S to S) rt i b0 c3 wear 8 i OS) § HH 均8 S) 〇o W) ω S cd 萏S) 1 S to B&gt; 〇i hJ PQ k4 CQ 8 SS Ο ω υ 8 ω U ω u S ss ω -1 S ω j W Η -1 W hJ S wj S s ω j ω hj S ω Mixed Plh *&quot;HF-H &lt;3 &lt;N ! 00 &lt; (N 1 1 ! 〇\ &lt;Ν νο &lt; (Ν 2 &lt;卜S r»*H CN CN 1 inch | 卜1 ΟΟ &lt; (Ν 1 ο ψ Ή C &lt;Ν 1 &lt; (N 1 ΓΛ S inch η s ο FH s S 1 Ή 5 S s yn (N 1 152219.doc •100· 201130494

1(N&lt; SEQ ID No C^i S inch SS s 5ν ο OO CN o (N 〇o ο (N CO 〇〇〇m 〇VO ΓΛ 〇P; o OO m 〇C\ soo inch oo 5 o JO OO o 〇Λ Ο cd ο ο ο ο d〇ό〇00 C10 oc ΰύ σ3 Οΰ ϋ0 σ5 Ο ωι υ ο 〇ΰ ΰύ ω) 芘cd cd cd 00 cd c〇cd OX) ω) o 荅H o &amp; Bp 〇υ o cd oooo Ώ) cd cd cd 0J) a λ λ b〇W) oe H u if oo tb 8d b〇όΰ Λ ο ό0 σ3 Λ Gt〇ω) cd cd cd &amp;0 cd cd cd OD W H bp S) bJO bp 1 o 8 op bfl Λ σ3 (3) S cd όΰ bp o I HHHH ci cd (3) ap S) 0ΰ BW) bO cd W) tofi cd cd cd DO s cd &amp; 0 o 荅HH a λ λ ο bJ) (3) ω) cd b£) Q ω) &amp; £) bfi bb cd 磬ο 苕Η Η So σ3 8 &amp; W) Ώ) § cd § ο Η Η Η Η i to wear So cd So Ώ) cd cd cd W) 1 W) W) | HHS) 灿 bO W) o 0 cd 1 op Λ oi 8 cd i) DO H H sb SS) ib 00 W) S) Dad ob〇Λ Cd Λ o cib (Λ op HHH 13 oc^ W) dD 00 cd o cd dfi cd W) (2) gJ o cd υ υ eg W) 运too to 0 S) 1 &amp;0 ω cd 萏δ £ Η (b) Β ω ) ss &amp; 孽 S • 4-1 eg) &gt;· S) H [: S) ci S) 8) W) W) ts S) 芘o 00 cd Dad 0 bb 叻bp HH a cd t 1 σ3 OX) s 8 〇W i O § όύ Η Η Η α bO 8 tb S3 o S) 芘s Λ 萏g HH 8 1 o W) to bfi i O ^b〇HHH ^) 8 8 square W) § os S) s cd 萏Si H part S1 0 1 tb U) 〇β t: t: W) S) W) H (di) glucoside aa gg S) a cd cd o bh cd ap H 匕cd O ooo W) cd oos 60 cd o W) +- » i OS) CC cd 00 HHE 芘c« 00 Λ ω) cd O oo cd oo Λ o cd υ OJO c3 t: 〇芘Μ cd cd Λ 〇tJ) d op H Sj cd bJ) 芘o cd cd Λ O CQ os 50 cd W) S) 8 C〇S) S 0D E bud Ο α I Μ a ω 穿 C〇Ο )ί) α 〇β ί: Η Η wa 0Χ) ΟΧ) CU0 ed 如钰c3 00 cd OX) Cd 狰b〇Λ cQ c3 CQ PQ WU ω υ ω u ω u WU ω υ ω u WU ω ω ω sw ω ώ ω s ω WWW s ω 1-) cone Ο 3 ι—Η tL( 3 i—H Uh s inch υ S ub O 1-H EXi S inch r H &amp; s § υ s (SU (X. s V〇(N u 3 (N CO 3 s VO s 00 s as § s CN iH Pl s y -^ Ui 3 PL, S 3 〇s 00 r«H Ph 3 (N (N u Uh 3 m (N U-H (X, s [Χι 3 &lt;n (NU 3 152 219.doc -101 - 201130494 s&lt; SEQ ID No 1049 1050 1051 1052 1053 1054 1055 1_ 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 Sequence Ο ο ο CO 芘dp ωο ο ο ο ο cc cc cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd cd GO ) ) ) ) ) ) ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' £ a O o another ao 磬 oe 0 1 i bp o S) — i CU) 1 磬og Ώ) s 8 ua dp o 8 〇tb (3⁄4 5 dJO cd &amp;X) W) | 6 W) 〇o Λ g3 ooo (J Λ 00 GJ} tb s Λ ο ο ο bfi δ 8 cd S 00 1 磬υ 8 〇W) DO S) tb 1 Οΰ 1 磬ο 8 W) 〇〇W) o sweep o W) g § 〇β bO E bX) Dad i ω) ω § 93 Total S) β s Η Η 1 S) • S g§ cd ω) ο ο tb bp i ο 00 § ω) a &amp;〇tb B | 〇 CO) Λ Λ 爸 Dad cd 迓 OJO ao OJO 8 Sweep W) 8 KJ i 0 1 00 ωι S) s υ ο 1 -4-· § Si 1 Si E g) W) ϋ 扛ωι ο te ω cccatcggcacaaacatcctTTTTTgaagttaccgtttt MS cd Total Si i § B ϋ i) — 1 i O OJO EHS o 芘ω 8 OW) Dad cd S) c i 0 1 8 〇to i 0 α 1 u 8 Ο Λ 8 Ο ω dad cd ο tb Λ W) Η Η S) ο ο ο ο ο ο ο 1 Ο g S) § 00 Η Η [: 1 ο ο ο § Ο ο ο μ wear cd Ο ω) a S) cd S) di) name i O 〇β 0 1 ο 芳 cd s ϋ e cd 诖 cd 笤Η ω) ο ο 芘 00 t3 8 λ e 8 square function m Ffl DQ a m S ω u W u SW uss mountain US ω s ω s PJ S ss ω 3 ω ω ·_! ω 3 tQ FPL name ARHGEF54 ARHGEF510 ARHGEF513 ARHGEF523 ARHGEF53 ARHGEF57 ARHGEF514 ARHGEF517 ARHGEF520 ARHGEF524 ARHGEF527 ARHGEF528 ARHGEF51 ARHGEF52 ARHGEF55 ARHGEF56 ARHGEF58 ARHGEF59 ARHGEF511 ARHGEF512 ARHGEF515 ARHGEF516 ARHGEF518 ARHGEF519 ARHGEF521 ARHGEF522 ARHGEF525 ARHGEF526 152219.doc •102- 201130494

Ez&lt; SEQ ID No SEQ oo o On 〇 o SO CN OO o ro oo ozo U^) 00 o Ό 00 o O 00 oo o ON 00 o ο O (N On 〇m 〇&gt; o ο OS o 〇 \ oo 00 On 〇On 〇\ 〇oo T—^ ο r—H ο ο BS) W) Οΰ g) a ο b〇t3 ο ο wear DX) cd cd cd a cd cd W) W) cd bfi op 0 1 sao DO Λ 8 W) wear oa bb cd cd cd CJ) cd cd Λ (3) ω) § b bfi 〇8 ω) ο 芘ο ts cd S3 Ώ) § Si _g) ϋ e HHU) s S) cd S) Ua όΧ ) ) ) ) ) ) ) ) όΰ $ $ $ όΰ $ όΰ όΰ 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 03 Bo cd cd to 〇〇β t»0 § 00 (3⁄4 cd cd U cd § C5〇cd W) _g) 0 β HE: H 1 S) 1 ο 扛ο &amp; bb 5 λ CJ) Λ aa GO W ) ae H cd wear GO cd 00 Λ cd d〇Λ {SO Λ 6 &amp; 00 cd 00 cd a ob cd W) wear KJ 0JD W) 〇H fc g) S) ob GO I g) tib cd cd cd b0 (3⁄4 0D 〇吾HHH o i2 ci ω) cd ooo bfl bfi DO 〇op ω) § i) § HHH cd W) 00 oo cd S) Pan S) ci W) so ci cd W) g HHH fe) Ώ) W) bi) o | W) SSS) i ο i) (b) t: W) cd Ώ) § ω) Tb 芘bb cd goods o 50 Λ Λ Λ Λ Λ t 苷 cd ο S) bi) cd ΟΧ) Gfi cd (DO bX) 芘00 cd I g) 1 ^bO HH to b0 cd b〇υ e W)芘o 芘ω S cd 萏Λ GJ) s [: H soa bb M dad S3 8 •4-1 i 8 cd S) HHW) o W) W) Wear W) s S) cd cd cd ou cd bp HH Λ & & & & & & & & ) ) Σ3 tb square cd 00 as DO i O § Η Η wi Β ο ubi S ω) &amp; S cd 萏S) H 1 g) o tb i 8 cd SS 0X) [: HHS) S) S) W) rt db υ 萏 萏 )) Ο CJ) ξ§ S Guide dp ω) λ 1 &amp; 0 13 g) §8 tb ο 1 ο S) Οβ § 1 dad ω) a, s cd 萏t HH 13 CJ ti i S) ω s Ώ) 1 Λ ffl H-) CQ PQ wu ω u ω u WU ω υ ω u ω u ω u ω ω ω h-1 W ω ω hj W hJ ω ω ω hj ω ω hj ω hj ω hi ω ω 练 Clh inch QH ω X/l tp—HQHW m QH tq C/DQH ω c/o QH s, etc. QH* WC/D (N inch QH ω mm inch Q Η WV〇i—HQHWC/D QQH ω QHW ΚΠ QH ω CO QH ω 00 QH ω a) QH ω 00 QH ω oo 吞 Q ω mo QHW ai ^-HQHWC/D 卜QH ω 00 oo QH PQ ζΛ inch Q Η m QHWC/D QQ ω ω 00 inch Q Η ω χη Q ω m inch QH s 152219.doc •103- 201130494 t7(N&lt SEQ ID No Ο oo oo ο o ο O ^•H CN m inch Ι^Μ ν〇1-Η 卜r· Η 00 ON •r^ r^3 r*H (N CN CN CN T—H 00 CN OS &lt;N omt··^ ΓΛ όΰ d〇C〇0 cd 00 1 芘dD 00 op 1 — cd ib 芘o cd 0£) cd cd o W) o Buckle 0 1 DO 5 &amp;p Ώ) ω §8 &amp;0 i GO ω) cd ed cd OD d£ &amp;0 aoo OX) DO Λ wear bD 1 碧ο _ S) S) Potential ο a tb σ3 &D 1 磬Ο ϊ ω) ω) ο 00 DC u § S) i 磬0 g) CJ) 1 wen 8 S) wear f Λ I face do § 2 5 00 gg 〇 &quot;Sd cd § 碁 _ W) S) gg 磬ωο Bb cd wear DD calendar ω) W) 〇DD 〇Q ω) δ S 〇8 Ώ) cd § Μ Ο e &amp;D i ω) s if ο cd Μ 1 磬ο 2 §0 s 8) 芘S) I 0D 1 ΟΧ) 〇〇e ω) 00 § λ ο SS) Jun a dad cd f W) top side o ub sc^ 00 i 8 C〇 〇β W) 5) ω) W) so 8 S) s cd 萏λ sb〇 To to Sb cd & 8 〇i O i) 5 bQ HHHH o W) | rt a 6 § I5 σ3 Si S) Ώ) Ώ) 仁 W) 8 op Si i 0 S) S bG _ 8 1 8 a S) na 〇J〇s cd u S) 目 ω) 8 运b〇ω) s &amp ; 1 &D Η W) S) a ·&lt;-» as Ώ Ώ s t3 o CJ S) o S) Total Λ ω) op op i 1 bO _ bp S) cd i & 〇β &amp Island cd Ώ) δ g H | oeoosoo to i 8 cd S, S 00 H o Pan U) W) 萏s&gt; bJ) t3 8) Wear cd 萏&amp;&quot;G oe 8 o 0 1 S5 sogg) u E (2) DJO aa W) o ϋ 8 ΐό S o td ω S Λ 萏 s> H s ts o OD Ώ) W) o -1 ffl Hl PQ CQ , -1 ffl ω υ s 8 UJ US PQ U ω υ ω υ S ta s ω ω ω ss S ω η-IS ω hj ω hJ ω ω tij 练P mg C/D hJ 〇ϋ 00 i GO 〇o Os i C/) hJ 〇ϋ (N 00 〇〇mg CO ο VO 00 00 〇ϋ GO GO GO 〇 〇 〇 CO CN CN CN CN CN CN CN CN CN CN 〇00 〇〇00 5 00 oo a&gt; CO 〇〇00 o 〇(Ν , 00 Ο ϋ in , 00 〇ϋ v〇t 00 〇〇on § 00 〇ϋ oo in hJ 〇o GO 〇o 00 o ϋ 152219 .doc •104· 201130494

SEQ ID No CN ΓΟ r·^ m co inch ΓΟ mm Γ- γο 〇〇CO 0\ m 〇1-H iH inch CN inch m inch inch inch v inch inch 00 a\ inch 0 1··Η &lt;N t— H m inch &lt;n « ^ in l〇v〇卜 yr\ calving 00 r—H ON T*~H sg] ω: CUD ΰΰ ω) S) CQ b£ W) oooo OX] Μ W) o &amp o 83 gD &amp; S) S3 ooo Si a | &amp; ooo 0 1 o cd tb if oo W) soe O ts OS] a ts § o to s 13 e 〇CQ draw 0 1 1 if si W1 § s 5 § Sd ωι 0 E a cd aa Sq 1 a tb U δι ωι ο Ε Η S) knot ο Μ e ο &amp; such as to u 3d § Si ωι o P o wear W3 cd M S1 o tb cd cd cd bC cd cd Cd ec 迓B &amp;〇〇〇〇爸爸&amp; 5§ S) W3 〇I 〇〇〇&amp; S) δ ο ο cd 1 Λ Sweep S) 1 0£ 1 u Μ f Ο ί Η &amp; Lane Si ο ο ο ο ο ο ο i CJ cd i) CJ] Giant H &amp; tfl W3 &amp; td S) Taste 3 萏δ a &amp;&amp; 1 &amp; i 〇cd S 5 0 _ ed a £P 6 knot W3 ts &amp; 5 Λ 萏Sa _ 6 a knot u 13 u tb 0£ ai O cd Ac tb 0£ c« td b£ &amp; o W3 s WQ ts W) cd eQ ce 〇tb cd ap 1 00 cd W) cd cd 0 d Λ d ed ce Λ ϋ i 〇 cd &amp; δ£ ο s § Sa CQ uniform δ 13 W) wear cd 萏cd 茗Ο td Ο Ο 1 cd e 〇O i 〇Cd S&gt; cd C3 b£ — — — -H c 爸 c c〇〇 cd ce ts CQ W) 13 &amp; cd s total cd 苕b£ O | S) 3d ai 〇cd i) 00 〇1 0 o 0 0 W) 0 CQ CQ 0Q hJ CQ CQ hJ PQ hJ PQ hJ CQ cn ω u tQ U ω u U ω U s ω ο us 3 PQ ω s tD w ω ω hJ PQ tQ HJ PQ ω hJ 铢mm S tQ hJ cu ON s ω 0-. ro cn s tq PQ CU m ω Oh (N m ί αί oo (N ms € m ί S 0. 芝 S a ω € ω (x 00 ms ω om ί PQ CU to HI s ω CU ?! m ί νη (Ν m ua CU o ΓΛ m ω CU ms 3 CU CN m ί w € ms W 0- P; S ω r-&gt; s 3 CU &lt;NS 卜 ί w iJ 0-1 00 S iJQ CU σ\ S ω 〇(N cn ί ω hJ CU ΓΛ s αί s s ω CU 152219.doc •105- 201130494 SEQ ID No 1161 1162 1163 Sequence ts W) u Dad ao S] sou S] i 〇cd to — 60 ed is bD U3 bJO ed OD Λ to cd another o td S) Wear C3 萏e〇 Ft 60 eQ W3 Λ B 5 &amp;p W) 1 6 ts Function 3 hJ FPL name PLEKHA327 PLEKHA331 PLEKHA332

152219.doc -106- 201130494

9&lt;n&lt; SEQ ID No inch v〇v〇 Bu VO oo On ο 卜 (Ν 1-^ rn 寸 卜 JO 00 ON 卜 o 00 00 (N OO m 00 1—^ cd 1 cd te 00 ϊ Μ -j -» 1 α cd ο i ο Ώ) 0 cd cd Ofi a 00 cd cd DO 1 萏ω) Ο to cd Λ cd OX) cd cd cd Ofl W) o I H 荏 cd W) ao W) cd o 00 C3 £ S) 〇cd ο Η Η Η cd Si ω) a ti) da t3 cd 迓3) cd 0 H 1 M bD S) S) e Pan a S) λ u t3 H 1 S) a ϋ ο ; a 1 b£) S cd DO bp o HHH ts Dad op ωι o ti § § S c« b〇W) o £ H 8 όβ cd 萏&amp;b cd 〇1 〇Ρ Η Η Η if ο i cd bfi cd OJD toi ) dp S) ts M cd to Λ OJQ g HHH cd W) OD 60 cd W) &amp;0 s 8) Λ &amp; 1 〇〇C0 运 C0 cd Η Η Η S) cd cd W) o CJ υ t : oo υ t: 0 § S) H 8 00 1 S3 3) ti〇1 〇β ig) § bO W) bJ) 8 Special 5 13 〇 6 M wear cd 萏S) ω si) 60 | c 萏i S i 8 a S) HHH b〇S) sss S) 1 § a dad cd 0 &quot;So cd bO HH cd cd 萏1 &quot;Sb o bO Λ CO cd pull cd cd Λ bitter S) gg) 1 S) GO (2) HH 0 ο 芘ο 1 ui CiO td 0 00 Λ Ώ) 3) -♦-* 1 Kt § s S) ω S 1 CIO s-* &amp; 8 cd % ω) forget u Μ s S) s tb s ω ι 芘 0 OD § cd 荔st 00 DD tuo 1 GO cd PQ OQ ω u PQ U ω u ω υ WU ω U ω ω W ω h-3 W sa ω W ω PQ kJ ω 铢CM 00 s HH m 00 5 2 00 00 οο 2 〇 OO 2 00 2 OO 3 (Ν 00 〇 00 2 g 5 00 00 ON 00 2 〇SS oo 2 CN OO 2 m 00 卜^-H 00 2 00 00 152219.doc -107· 201130494

Lz¥ SEQ ID No in 00 v〇00 oo 1-^ 00 00 On 00 Ο σ\ *—Η 〇Ν Η ON m OS 1&quot; — r*H in ON Os ON o fH oj S CN s (N 〇 e Λ 爸 dad i 1 a 00 o 00 cd o S) o 0D Λ B cd tb ΰβ ci λ s &amp;β IM 〇 _ 1 I gg &amp; a 00 Sb cd bud s ω 0 目 0β S) ω) DO 1 bb cd S GO &lt;au OQ W) oet § 25 〇CO) S) 0 1 o Ώ) cd wear bD 1 蓉 a &amp; 〇§8 δ i total ΰΰ cd DO cd Λ Λ ό〇 ω) 1 C3 00 〇β Ο a Ώ) ω) λ 8 tb 1 1 u ί ο Β ϊ 0D a&gt; η W) i S) 00 § s 00 13 W) s cd 荔S) s Nie 1 OX) op W) g) i O § b〇EW) g) ωι DO bO W) ω s tb s&gt; E tb b〇芘8 8 Ο i 0 cd S bO (b) &amp; 0 1 8 W) a S3 υ ts ω η S) ί S ) 芘dp ο S) a U) cd i α cd 钰00 CJ) i, Λ 芘ts 8 wear cS tb Μ S &amp; cd cd 1 00 00 to GO Gfl IS 8 ω i 0 1 s bO HH sos, 8 o 8) § bp 芘a 1 falls S) t 00 i 1 gs ao OJO to ω) i 8 cd ω) Η S) όβ υ 8) Β part b〇td ω s Ώ) Si H si W) 8 〇 g) VJ m hJ PQ ω u ω υ au ω ο ω υ S s ω hJ Pl ω hj S ω hJ ss PJ hJ ω hj ω h -i ω N N-1 OKQ o Os SQ Oh &lt; 〇k Q o 寸 κ Q o 卜 XQ Oh &lt; o ι^Η XQ PL, &lt; Ο inch κ Q Ο XS &lt;N ffi Q 〇ma Q (3⁄4 &lt; 〇Q (X &lt; 〇VO ffi Q o 00 XQ &lt; 〇On ffi Q cu &lt; ϋ rs XQ o ro SQ CL, C 〇ms Q 〇VO ffi Q o 卜ffi Q O. &lt; 〇00 XQ cu &lt; 〇 152219.doc -108- 201130494 [Table Description] Table 1 - Unmodified dsRNA targeting human IL-18 gene. Uppercase alphabets indicate RNA nucleotides; Table 2 - Modified dsRNAs that target the human IL-18 gene. Uppercase letters indicate RNA nucleotides, lowercase letters "c", "g", "a" and "," indicate 2, 〇 _ methyl modified nucleotides, "s" indicates phosphorothioate, "dT" indicates Deoxythymidine, "OMedT" means 5,-〇-mercapto-deoxythymidine, "p" means 5, the terminal 5,-phosphate group of each φ dsRNA strand, and rf" represents the aforementioned symbol 21-fluoro modification of the indicated nucleotides; Table 3 - Characterization of dsRNA to stem of human IL-18: Activity assay for dose response in HCT-116 cells. 1C 50 : 50% inhibitory concentration, 1C 80 : 80% inhibitory concentration, ic 20 : 20% inhibitory concentration; Table 4 - Characterization of dsRNA targeting human IL-18: stability and cytokine induction. 11⁄2: half-life of one strand as defined in the example, PBMc: human peripheral blood mononuclear cells; φ Table 5 - unmodified dsRNA targeting the murine IL-18 gene. Uppercase alphabets indicate RNA nucleotides; Table 6 - Modified dsRNAs that target the murine IL-18 gene. Uppercase letters indicate RNA nucleotides, lowercase letters "c", rg", ra" and ru" indicate 2, 〇-methyl modified nucleotides, "s" indicates phosphorothioate, and "dT" indicates Oxythymidine; Table 7 - Characterization of dsRNA of stem murine IL-18: Activity assay for dose response in RAW264.7 cells. 1C 50 : 50% inhibitory concentration, 1C 80 : 80% inhibitory concentration, ic 20 : 20% inhibitory concentration. Stability and cells 152219.doc -109- 201130494 Hormone induction. : half-life of one strand as defined in the example, PBMC: human peripheral blood mononuclear cells; Table 8 - Sequence of bDNA probes for the determination of human IL-18; LE = label extender, CE = Capture extension agent, BL = blocking probe; Table 9 - Sequence of the bDNA probe used to determine human GAPDH. LE = label extension, CE = capture extension, BL = blocking probe; Table 10 - sequence for determination of murine IL-1 8 bDNA probe; LE = label extension "CE = capture extension, Bl = blocking probe; Table 11 - Sequence of the bDNA probe used to determine murine GAPDH. LE = label extension, CE = capture extension, bl = blocking probe; Table 12 - unmodified dsRNA directed to the human IL-1 8 gene and its modified counterpart. Uppercase letters indicate RN A nucleotides, lowercase letters "c", "g", "a" and "u" indicate 2, 〇_曱-modified nucleotides, and "s" indicates phosphorothioate 'dT "Deoxy Thionine, "5,-〇MedT" means 5·-0-methyl-deoxythymidine'"p" means 5, the 5, the phosphate group, And "f" represents a 2,-fluoro modification of the nucleotide represented by the aforementioned symbol; Table 13 - Unmodified dsRNA to the murine il-18 gene and modified counterpart thereof. Capital letters indicate RNA nucleotides, lowercase letters r ^", "g", "a", and "u" indicate 2, 〇-methyl modified nucleotides, "s" indicates thio acid filling, "dT "Deoxythymidine; Table 14 - Bioinformatics selection of potential off-targets; Table 15_ Ideally matched siRNAs for predicting off-target sites; Table 16_ Potential off-target target sites, mismatched sites, and (medium target) off-target activity 1522l9.doc •110- 201130494 Table 17-A43 Dose response analysis of selected off-targets in 1 cell; Table 18 - bDNA probe set for endogenous analysis of dsRNA comprising paired sequence 239/240 off-target-1; Table 19 - bDNA probe sets for endogenous analysis of dsRNAs containing paired sequence 239/240 off-target-7; Table 20 - bDNA for endogenous analysis of dsRNA containing paired sequence 255/256 off-target-1 Probe set; φ Table 21 - bDNA probe set for endogenous analysis of dsRNA containing paired sequence 255/256 off-target-7; Table 22 - Internal for dsRNA containing paired sequence 255/256 off-target-13 BDNA probe set for source analysis; Table 23 - bDNA probe set for endogenous analysis of dsRNA containing paired sequence 165/1 66 off-target-2; Table 2 4-BDNA probe set for endogenous analysis of dsRNA containing paired sequence 165/1 66 off-target-7; φ Table 25 - Endogenous analysis of dsRNA containing paired sequence 165/166 off-target-12 bDNA probe set; Table 26 - bDNA probe set for endogenous analysis of human IL-18; and Table 27 - bDNA probe set for endogenous analysis of human GAPDH. [Simplified Schematic] Figure 1 - dsRNA targeting human IL-18 gene ("IL-18 siRNA") inhibits LPS-induced IL-18 protein secretion and mRNA expression in THP-1 cells. 152219.doc 201130494 &lt;110&gt;Swiss Business Herfoe Menglaruo Co., Ltd. &lt;120&gt; Composition and method for inhibiting IL-18 gene expression &lt;130&gt; 26499 &lt;140&gt; 099144039 &lt;141&gt; 2010-12- 15 &lt;150&gt; 09179873.6 &lt;151&gt; 2009-12-18 &lt;160〉]203

&lt;210> 1 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 1 uguucacugu ucaaaacga 19 &lt;210 〉 2 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 2 ucguuuugaa cagugaaca 19 &lt;210> 3 &lt ;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 3 guucacuguu caaaacgaa 19 152219 - Sequence Listing.doc 201130494 &lt; 210> 4 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 4 uucguumiga acagugaac 19 &lt;210> 5 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 5 uucacuguuc aaaacgaag 19 &lt;210&gt; 6 &lt;211&gt 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 6 cuucguuuug aacagugaa 19 &lt;210&gt; 7 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA's sensible stock &lt;400&gt; 7 152219· Sequence Listing.doc 201130494 ucauacgaag gauacuuuc 19 &lt;210&gt; 8 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense of dsRNA Shares &lt;400&gt; 8 gaaaguaucc uucguauga 19

&lt;210> 9 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 9 cccaggacau gauaauaag 19 &lt;210 〉 10 &lt;211> 19 &lt;212> RNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400> 10 cuuauuauca uguccuggg 19 &lt;210> 11 &lt ;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt;220> 152219·Sequence list.doc 201130494 &lt;223> Description of artificial sequence··ssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssssss ; 210> 12 &lt; 211 > 19 &lt; 212 &gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Antisense Strand of dsRNA &lt;400 &gt; 12 gcuagucuuc guuuugaac 19 &lt;210&gt; 13 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 13 guauguauaa agauagcca 19 &lt;210&gt; 14 &lt; 211 &gt; 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Unit Meaning &lt; 400 &gt; 14 uggcuaucuu uauacauac 19

&lt;210&gt; 15 &lt;211> 19 &lt;212&gt; RNA 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 15 cauugaccaa ggaaaucgg 19 &lt;210&gt; 16 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence_ &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 16 ccgauuuccu Ugucuaug 19 &lt;210&gt; 17 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA

&lt;400> 17 caaacuauuu gucgcagga 19 &lt;210> 18 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 18 uccugcgaca aauaguuug 19 152219-sequence table.doc 201130494 &lt;210> 19 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: meaning of dsRNA Stock &lt;400&gt; 19 acucucuccu gugagaaca 19 &lt;210&gt; 20 &lt;211&gt; 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt;&lt;220&gt;&lt;223&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 20 uguucucaca ggagagagu 19 &lt;210&gt; 21 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; 223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400> 21 Uuuauugaca auacgcuuu 19 &lt;210> 22 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;400> 22 152219 List .doc 201130494 aaagcguauu gucaauaaa 19 &lt;210> 23 &lt;211> 19 &lt;212> RNA &lt;213 〉Artifical sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA sine stock &lt;400> 23 cuuccucucg caacaaacu 19

&lt;210&gt; 24 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 24 aguuuguugc gagaggaag 19

&lt;210&gt; 25 &lt;211&gt; 19 ^ &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 25 gaccauauuu auuauaagu 19 &lt;210&gt; 26 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence&lt;220> 152219-SEQ ID NO: doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 26 acuuauaaua Aauaugguc 19 &lt;210&gt; 27 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA's sensible stock &lt;400> 27 ugaccaagga aaucggccu 19 &lt ;210> 28 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 28 aggccgauuu ccuugguca 19 &lt;210> 29 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sensed strand of dsRNA &lt;400&gt; 29 ucaaaacgaa gacuagcua 19

&lt;210> 30 &lt;211> 19 &lt;212&gt; RNA 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 30 uagcuagucu ucguuuuga 19 &lt;210> 31 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence^ &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 31 gaaucuucau Cauacgaag 19 &lt;210> 32 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;400> 32 cuucguauga ugaagauuc 19 &lt;210> 33 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400 〉 33 gggauagauc uauaauguu 19 152219-sequence table.doc 201130494 &lt;210&gt; 34 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense of dsRNA Stock &lt;400> 34 aacauuauag aucuauccc 19 &lt;210> 35 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt; 400> 35 cuauuugucg caggaauaa 19 &lt;210> 36 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; Uuauuccugc gacaaauag 19 &lt;210&gt; 37 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> <223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 37 •10·

152219 - Sequence Listing.doc 201130494 ucuauuugaa gauaugacu 19 &lt;210> 38 &lt;211&gt; 19 <212> RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt; 400> 38 agucauaucu ucaaauaga 19

&lt;210&gt; 39 &lt;211&gt; 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA sine stock &lt;400&gt; 39 caacaaacua uuugucgca 19 &lt;210 〉 40 &lt;211> 19 • &lt;212> Legs&lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 40 ugcgacaaau aguuuguug 19 &lt;210> 41 &lt;211> 19 &lt;212&gt; RNA <213>Artificial sequence &lt;220> • 11 152219 - Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 41 aucuucauc-a Uacgaagga 19 &lt;210> 42 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 42 uccuucguau gaugaagau 19 &lt ;210> 43 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 43 cucucgcaac aaacuauuu 19 &lt;210〉 44 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: d Antisense stock of sRNA &lt;400〉 44 aaauaguuug uugcgagag 19

&lt;210> 45 &lt;211&gt; 19 &lt;212&gt; RNA 12·

152219-Sequence List.doc 201130494 &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 45 ugaaucuuca ucauacgaa 19 &lt;210> 46 &lt;211> 19 &lt ; 212 &gt; RNA &lt; 213 &gt; 213 > Artificial Sequence Call &lt; 220 > &lt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 46 uucguaugau gaagauuca 19 &lt;210> 47 &lt;211> 19 &lt;212 〉 RNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA

&lt;400&gt; 47 cagaccuucc agaucgcuu 19 &lt;210> 48 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400 〉 48 aagcgaucug gaaggucug 19 •13 152219-sequence table.doc 201130494 &lt;210&gt; 49 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: dsRNA Sense stock &lt;400&gt; 49 cagaucgcuu ccucucgca 19 &lt;210&gt; 50 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 50 ugcgagagga agcgaucug 19 &lt;210> 51 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 51 cuagagguau ggcuguaac 19 &lt;210> 52 &lt;211> 19 &lt;212> RNA &lt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 52 - 14 152219-SEQ ID NO.doc 201130494 guuacagcca uaccucuag 19 &lt;210&gt; 53 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 53 auuuauugac aauacgcuu 19

&lt;210&gt; 54 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 54 aagcguauug ucaauaaau 19 &lt;210&gt 55 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 55 acaauacgcu uuacuuuau 19 &lt;210&gt; 56 &lt 211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt;220&gt; -15 152219·SEQ ID NO: doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 56 auaaaguaaa gcguauugu 19 &lt;210> 57 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 57 acgaaggaua cuuucuagc 19 &lt;210&gt 58 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 58 gcuagaaagu auccuucgu 19 &lt;210&gt; 59 &lt;;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence The dsRNA sense Unit &lt; 400> 59 ggaauugucu cccagugca 19

&lt;210&gt; 60 &lt;211> 19 &lt;212> RNA 16-

152219·Sequence List.doc 201130494 &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 60 ugcacuggga gacaauucc 19 &lt;210> 61 &lt;211> 19 &lt ;212&gt; RNA &lt;213>Artificial sequence^&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 61 cagucuacac agcuucggg 19 &lt;210> 62 &lt;211> 19 &lt;212&gt RNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA

&lt;400&gt; 62 cccgaagcug uguagacug 19 &lt;210> 63 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400 〉 63 aucauacgaa ggauacuuu 19 -17 1522〗 9-sequence table.doc 201130494 &lt;210&gt; 64 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Antisense stock of dsRNA &lt;400&gt; 64 aaaguauccu ucguaugau 19 &lt;210&gt; 65 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Stocks &lt;400&gt; 65 uugaaucuuc aucauacga 19 &lt;210&gt; 66 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA ;400&gt; 66 ucguaugaug aagauucaa 19 &lt;210> 67 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 67 -18·

1522丨9_ Sequence Table.doc 201130494 uuugaaucuu caucauacg 19 &lt;210&gt; 68 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense of dsRNA Shares &lt;400&gt; 68 cguaugauga agauucaaa 19

&lt;210> 69 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 69 gaucgcuucc ucucgcaac 19 &lt;210&gt 70 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 70 guugcgagag gaagcgauc 19 &lt;210> 71 &lt;;211> 19 &lt;212> RNA &lt;213>Artificial sequence <220> •19 152219-Sequence table.doc 201130494 &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 71 gagguauggc uguaacuau 19 &lt ;210> 72 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 72 auaguuacag ccauaccuc 19 &lt;210〉 73 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 73 ucccaggaca ugauaauaa 19 &lt;210&gt; 74 &lt; 211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Anti-sense stock &lt;400&gt; 74 uuauuaucau guccuggga 19

&lt;210&gt; 75 &lt;211> 19 &lt;212&gt; RNA 20·

152219·Sequence List.doc 201130494 &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 75 ucuacacagc uucgggaag 19 &lt;210> 76 &lt;211> 19 &lt ;212> RNA &lt; 213 > Artificial Sequence • &lt; 220 > &lt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 76 cuucccgaag cuguguaga 19 &lt;210> 77 &lt;211> 19 &lt;212 〉 RNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA

&lt;400&gt; 77 ucucgcaaca aacuauuug 19 &lt;210&gt; 78 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400 〉 78 caaauaguuu guugcgaga 19 -21 152219 · Sequence Listing.doc 201130494 &lt;210> 79 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: dsRNA Sense stock &lt;400&gt; 79 gaaucacuug cacuccgga 19 &lt;210&gt; 80 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 80 uccggagugc aagugauuc 19 &lt;210> 81 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 81 ugaaucuaaa uuaucaguc 19 &lt;210&gt; 82 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 82 - 22 152219-Sequence table.doc 201130494 gacugauaau uuagauuca 19 &lt;210〉 83 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 83 gaauccuccu gauaacauc 19

&lt;210> 84 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 84 gauguuauca ggaggauuc 19 &lt;210 〉 85 &lt;211&gt; 19

• &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 85 agagguaugg cuguaacua 19 &lt;210> 86 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt;220> -23- 152219-SEQ ID NO.doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 86 uaguuacagc cauaccucu 19 &lt;210> 87 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 87 gucccaggac augauaaua 19 &lt;210&gt; 88 &lt;211 〉 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 88 uauuaucaug uccugggac 19 &lt;210> 89 &lt;211> 19 &lt ;212&gt; RNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 89 gauaacauca aggauacaa 19

&lt;210> 90 &lt;211&gt; 19 &lt;212&gt; RNA -24 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> <223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400 〉 90 uuguauccuu gauguuauc 19 &lt;210> 91 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence

&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 91 acaaacuauu ugucgcagg 19 &lt;210> 92 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 92 ccugcgacaa auaguuugu 19 &lt;210> 93 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 93 aaggauacuu ucuagcuug 19 -25 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 94 &lt;211> 19 &lt;212&gt; RNA &lt;213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 94 caagcuagaa aguauccuu 19 &lt;210> 95 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 95 uauuaaaauu ucaugccgg 19 &lt;210> 96 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 96 ccggcaugaa auuuuaaua 19 &lt;210> 97 &lt;211 〉 19 &lt;212> RNA &lt; 213 > Artificial Sequence &lt; 220 > &lt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 97 -26 152219 · Sequence Listing.doc 201130494 uagccagccu agagguaug 19 &lt;210&gt; 98 &lt;211> 19 &lt;212> RNA &lt; 213 &gt; 213 &gt; 221 &lt; 223 &gt; 223 &gt; Description of artificial sequence: antisense strand of dsRNA &lt;400 &gt; 98 cauaccucua ggcuggcua 19

&lt;210> 99 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 99 uggcugcuga accaguaga 19 &lt;210 〉 100 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 100 ucuacugguu cagcagcca 19 &lt;210&gt; 101 &lt;;211> 19 &lt;212> RNA &lt;213>Artificial sequence&lt;220> •27 152219·Sequence table.doc 201130494 &lt;223> Description of artificial sequence: sRNA sine stock &lt;400> 101 agaaucacuii gcacuccgg 19 &lt;210&gt; 102 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 102 ccggagugca agugauucu 19 &lt;210&gt 103 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;400&gt; 103 auuaaaauuu caugccggg 19 &lt;210&gt; 104 &lt;;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223>Artificial sequence Said: dsRNA shares of antisense &lt; 400> 104

Cccggcauga aauuuuaau 19 &lt;210&gt; 105 &lt;211> 19 &lt;212&gt; RNA 28·

152219 · Sequence Listing.doc 201130494 &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400> 105 ugcagucuac acagcuucg 19 &lt;210> 106 &lt;211&gt; 19 &lt ;212> RNA &lt;213> artificial sequence

&lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 106 cgaagcugug uagacugca 19 &lt;210> 107 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400> 107 gaucuauaau guucacugu 19 &lt;210&gt; 108 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 108 acagugaaca uuauagauc 19 •29 152219-sequence table.doc 201130494 &lt;210&gt; 109 &lt;211&gt; 19 &lt;212> RNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 109 gcagucuaca cagcuucgg 19 &lt;210> 110 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 110 ccgaagcugu guagacugc 19 &lt;210&gt; 111 &lt;211> 19 &lt;212&gt; RNA <213>Artificial sequence &lt;220&gt;&lt;223 〉 Description of artificial sequence: sRNA suffix stock &lt;400&gt; 111 uuaaaauuuc augccgggc 19 &lt ; 210> 112 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 112 -30 1522丨9-order List .doc 201130494 gcccggcaug aaauuuuaa 19 &lt;210> 113 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400> 113 aacaaacuau uugucgcag 19

&lt;210> 114 &lt;211> 19 &lt;212> RNA <213> Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 114 cugcgacaaa uaguuuguu 19 &lt;210> 115 &lt;211> 19

• &lt;212&gt; RNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400> 115 aauuuauuga caauacgcu 19 &lt;210> 116 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt;220> -31 152219·SEQ ID NO:doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 116 agcguauugu caauaaauu 19 &lt;210&gt; 117 &lt;;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 117 aaaauuuca.u gccgggcgc 19 &lt;210&gt; 118 &lt; 211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 118 gcgcccggca ugaaauuuu 19 &lt;210> 119 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 119

Guguagugac gcaugcccu 19 &lt;210&gt; 120 &lt;211> 19 &lt;212&gt; RNA 32-

152219-Sequence List.doc 201130494 &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400> 120 agggcaugcg ucacuacac 19 &lt;210> 121 &lt;211&gt; 19 &lt ;212&gt; RNA &lt;213>Artificial sequence

&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 121 aaauuuauug acaauacgc 19 &lt;210> 122 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt; 〉 Description of artificial sequence: antisense stock of dsRNA

&lt;400&gt; 122 gcguauuguc aauaaauuu 19 &lt;210&gt; 123 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 123 auugaccaag gaaaucggc 19 -33· 152219·Sequence list.doc 201130494 &lt;210&gt; 124 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Antisense stock &lt;400&gt; 124 gccgauuucc uuggucaau 19 &lt;210> 125 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: meaning of dsRNA Stock &lt;400&gt; 125 uguagugacg caugcccuc 19 &lt;210> 126 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 400> 126 gagggcaugc gucacuaca 19 &lt;210&gt; 127 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 127 • 34 152219 · Sequence Listing.doc 201130494 ccggaccaua uuuauuaua 19 &lt;210&gt; 128 &lt;211&g t; 19 &lt;212> RNA &lt; 213 > artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 128 uauaauaaau augguccgg 19

&lt;210&gt; 129 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 129 agcca.gccua ga.ggua .ugg 19 &lt;210> 130 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Strand of dsRNA &lt;400&gt; 130 ccauaccucu aggcuggcu 19 &lt;210&gt; 131 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> -35 152219 · Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 131 guagugacgc augcccuca 19 &lt;210&gt; 132 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 132 Ugagggugug cguca.cuac 19 &lt;210> 133 &lt;211&gt; 19 &lt;232&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;400&gt; 133 gacgcaugcc Cucaauccc 19 &lt;210> 134 &lt;211> 19 &lt;212> RNA &lt;213>Artificial Sequence &lt;220> &lt;223>Artificial Sequence Description: antisense stock of dsRNA &lt;400> 134

Gggauugagg gcaugcguc 19 &lt;210&gt; 135 &lt;211> 19 &lt;212> RNA 36-

152219· Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400> 135 aaucuucauc auacgaagg 19 - &lt;210> 136 &lt;211> 19 &lt;212&gt; RNA &lt;213&gt; Artificial sequence 9 &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 136 ccuucguaug augaagauu 19 &lt;210> 137 &lt;211&gt; 19 &lt; 212> RNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA

&lt;400> 137 ggaaaucggc cucuauuug 19 &lt;210> 138 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> <223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 138 caaauagagg ccgauuucc 19 -37 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 139 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: dsRNA Stocks &lt;400> 139 ucagaccuuc cagaucgcu 19 &lt;210&gt; 140 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA ;400&gt; 140 agcgaucugg aaggucuga 19 &lt;210&gt; 141 &lt;211> 19 &lt;212> RNA &lt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: sRNA sensible stock &lt;400> 141 auaugacuga uucugacug 19 &lt;210&gt; 142 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 142 •38 ·

152219 - Sequence Listing.doc 201130494 cagucagaau cagucauau 19 &lt;210> 143 &lt;211&gt; 19 &lt;212> RNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 > Description of Artificial Sequence: Sensed Strands of dsRNA ;400&gt; 143 uugcacuccg gagguagag 19

&lt;210> 144 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 144 cucuaccucc ggagugcaa 19 &lt;210 〉 145 &lt;211> 19 <212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sense of dsRNA &lt;400&gt; 145 cuugcacucc ggagguaga 19 &lt;210> 146 &lt; 211 &gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> -39- 152219 - Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 146 ucuaccuccg gagugcaag 19 &lt;210> 147 &lt;211> 19 &lt;212&gt; RNA <213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 147 ugacgcaugc ccucaaucc 19 &lt;210〉 148 &lt; 211 &gt; 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt; 223 &gt; 223 &gt; 223 &gt; 223 &gt; 223 &gt;&lt;400&gt; 148 ggauugaggg caugcguca 19 &lt;210&gt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description: Sensed Shares of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 55-decanoate group" &lt;220> &lt; 221〉 modified—base -40-

152219-Sequence List.doc 201130494 &lt;222&gt; 1, 3, 4, 5, 7, 8, 10, 11, 12, 17 &lt;223>/modified base = "2'·0· thiol corresponding nucleus "Glycosylation" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;;222>2,6,9,13,14,15,16,18,19&lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 149

Uguacacugu ucaaaacgat t 21 &lt;210> 150 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221 〉 modified-base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 11, 18 &lt; 223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-sulfur Phosphate thymidine" &lt;220> &lt;221> modified_base &lt;221>1, 2, 3, 4, 5, 6,7, 8,9,10, 12,13, &lt;223>/modified Base = "2'-hydroxyl corresponding nucleotide" • 41 · 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 150 ucguuuugaa cagugaacat t 21 &lt;210&gt; 151 &lt;211> 21 &lt;212> DNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base == "nucleotide : Lack of 5'-filled acid base &lt;220〉 &Lt;221> modified-base &lt;222>1,3,4, 5, 7,8,10,11,12, 17 &lt;223>/modified base = "2'-0-methyl corresponding core &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base == "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221〉 modified A base &lt;222>2, 6,9, 13, 14, 15, 16,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 151 uguucacugu ucaaaacgat t 21 &lt;210&gt; 152 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> • 42·152219· Sequence Listing, doc 201130494 &lt;221&gt; modifiedbase &lt;222>1,11,18 &lt;223&gt;/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3, 4, 5, 6, 7, 8,9,10,12,13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400> 152 ucgumiugaa cagugaacat t 21 &lt;210&gt; 153 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221> modified_base &lt;222&gt; 1 ^ &lt;223>/modified base = "nucleotide: lack of 5'-phosphate base" &lt;220> &lt;221> modified-base &lt; 222>1, 3,4, 5, 7, 8, 10, 11,12, 17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/ground base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 6, 9,13 , 14, 15, 16,18,19 &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" -43- 152219 - Sequence Listing.doc 201130494 &lt;400> 153 uguucacugu ucaaaacgat t 21 &lt ;210> 154 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222 〉1, 4, 11,18 &lt;223>/modified base = "25-0 -methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221 〉 modified—base &lt;222>2, 3,5, 6, 7,8,9, 10, 12, 13, 14, 15, &lt;223>/modified base = "2'·hydroxy corresponding nucleoside Acid &lt;400&gt; 154 ucguuuugaa cagugaacat t 21 &lt;210&gt; 155 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" -44- 152219 - Sequence Listing.doc 201130494 &lt;;220>&lt;221&gt; modified_base &lt;222>1,3, 4,5, 7, 8,10,11, 12,17 &lt;223>/modified base = "2'-0-methyl corresponding Nucleotide &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>2, 6, 9,13,14, 15, 16,18, 19 &lt;223>/modified base = "2'· Hydroxyl corresponding nucleotide

&lt;400&gt; 155 uguucacugu ucaaaacgat t 21 &lt;210> 156 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 7,11,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>2, 3, 4, 5, 6, 8 , 9, 10,12, 13,14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 156 ucguuuugaa cagugaacat t 21 -45- 152219 · Sequence Listing.doc 201130494 &lt;210&gt; 157 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4, 5, 7, 8, 10, 11, 12, 17 &lt;223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5s-phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>2, 6,9, 13, 14,15, 16,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt 157 uguucacugu ucaaaacgat t 21 &lt;210> 158 &lt;211> 21 &lt;212&gt; DNA &lt;2]3&gt;Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220 〉 &lt;221〉 modified_base &lt;222>1, 2, 4, 5,6,7, 11,14,18 &lt;223>/modified base == "2'·deoxy-2'-fluorine corresponding Nucleotide -46· 1522〗 9. Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; rnodified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine &lt;220〉 &lt;221&gt; fflodified_base &lt;222>3, 8, 9, 10, 12,13,15,16,17, 19 &lt;223>/modified base = "25-hydroxy corresponding nucleoside Acid &lt;400&gt; 158 ucguuuugaa cagugaacat t 21

&lt;210&gt; 159 &lt;211&gt; 21 &lt;212&gt;212&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt; ' &lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt; 220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "5'-0-mercapto-thymidine" &lt;220> &lt;221> modified-base &lt;222>2,3, 4,5, 7,8, 10,11, 12, 17 &lt;223> / Modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-sulfur Phospho-ester thymidine" &lt;220> &lt;221> modified_base •47· 152219-sequence table.doc 201130494 &lt;222>6, 9,13,14, 15, 16,18, 19 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 159 tguucacugu ucaaaacgat t 21 &lt;210&gt; 160 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modifi Ed_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 59·phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>11,18 &lt;223>/ Modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "55-phosphorothioate thymidine &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3,4,5,6,7,8, 9, 10,12, 13, &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&lt;400&gt; 160 ucguuuugaa cagugaacat t 21 &lt;210> 161 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220> 1522]9·SEQ ID list. ·48· 201130494 &lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: missing 5' -phosphate group" &lt;220> &lt;221> modified_base &lt;221> 1 &lt;223>/modified base = "55-0-mercapto-thymidine" &lt;220> &lt;221> modified one Base

&lt;222>2,3,4, 5, 7, 8, 10,11, 12,17 &lt;223>/modified base = "2'_0·methyl corresponding nucleotide" &lt;220〉 &lt;;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modifiedbase &lt;222>6,9, 13 , 14, 15, 16, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 161 tguucacugu ucaaaacgat t 21

&lt;210> 162 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222>1, 11,18 &lt;223&gt;/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt; -49- 152219 - Sequence Listing.doc 201130494 &lt;221〉 Modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'·deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,4, 5, 6,7, 8, 9,10, 12, 13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 162 ucguuuugaa cagugaacat t 21 &lt;210&gt; 163 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "5'-0 ·曱基·thymidine” &lt;220〉 &lt;221&gt; modified_base &lt;222 2,3, 4,5, 7,8, 10,11,12, 17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; Modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>6,9, 13,14, 15, 16, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -50- 1522丨9· Sequence Listing.doc 201130494 &lt;400&gt; 163 tguucacugu ucaaaacgat t 21 &lt;210&gt; 164 &lt; 211 &gt; 21 &lt;212> DNA &lt; 213 &gt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221> modified_base • &lt;222>1 , 4, 11, 18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/ Modified base == "5'-thiophosphate thymidine" <220> &lt;221&gt; modified_base &lt;222&gt; 2, 3, 5, 6, 7, 8, 9, 10, 12, 13, 14 , 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 164

Ucguuuugaa cagugaacat t 21 &lt;210&gt; 165 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-decarboxylate group" -51 - 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "5'-0-methyl-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 7, 8,10, 11, 12,17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / Modified base = "5'-thiophosphate thymidine" &lt;220> &lt;221> modified_base &lt;222>6, 9, 13,14, 15,16, 18, 19 &lt;223>/ Modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 165 tgmicacugn ucaaaacgat t 21 &lt;210&gt; 166 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of the artificial sequence: antisense stock of dsRNA &lt;220〉 &lt;221〉 modified_base &lt;222>1,7, 11,18 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2, 3, 4, 5, 6, 8 , 9, 10, 12, 13, 14, -52 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "25_hydroxy corresponding nucleotide" &lt;400> 166 ucguuuugaa cagugaacat t 21 &lt; 210> 167 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: sRNA's sensible stock

&lt;220> &lt;221> modified base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "5'·0-methyl-thymidine" &lt;220&gt; <221> modified-base &lt;222>2, 3, 4, 5, 7, 8, 10 , 11, 12, 17 &lt; 223 > / modified base = "25-0 - thiol corresponding nucleotide" &lt; 220 > &lt; 221 > modified_base &lt; 222 > 21 &lt; 223 > / modified base Base = "5'-Dilogenated Phosphate Thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>6,9,13,14,15,16,18,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 167 tguucacugu ucaaaacgat t 21 &lt;210&gt; 168 &lt;211> 21 •53- 152219-sequence table.doc 201130494 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2,4, 5,6, 7,11,14, 18 &lt ;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt; 221 &gt; modified_ba.se &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3, 8,9 , 10,12, 13, 15,16,17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 168 ucguuuugaa cagugaacat t 21 &lt;210> 169 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / Modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4, 5, 7, 8, 10, 11,12 , 17 &lt; 223 > / modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221> modified a base • 54·

152219-Sequence List.doc 201130494 &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,6, 9,13,14,15, 16,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 169 uguucacugu ucaaaacgat t 21

&lt;210> 170 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified-base &lt;222> 11, 18 &lt;223>/ Modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate chest Glycoside &lt;220> &lt;221> modified-base &lt;222>1,2,3,4,5,6,7,8,9,10,12,13, &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 170 ucguuuugaa cagugaacat t 21 &lt;210> 171 -55- 152219-sequence table.doc 201130494 &lt;211&gt; 21 &lt;212> DNA &lt;213&gt; Sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5 '·phosphate group> &lt;220&gt;&lt;221&gt; modif Ied_base

&lt;222>1,3, 4, 5,7, 8, 10, 11, 12,17 &lt;223>/modified base = "2'·degas-2s·fluorine corresponding nucleotide" &lt;220&gt;&lt;221&gt; raodified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 6,9,13,14,15,16,18,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 171 uguucacugu ucaaaacgat t 21

&lt;210> 172 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222>1,11,18 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> • 56 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3,4,5,6,7,8 , 9, 10, 12, 13, 14, &lt;223>/modified base = "Γ·hydroxy corresponding nucleotide" &lt;400> 172 ucguuuugaa cagugaacat t 21 &lt;210&gt; 173 β &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Base = "nucleotide: lack of V-phosphate group" &lt;220〉 &lt;221&gt; modified_base

&lt;222&gt; 1, 3, 4, 5, 7, 8, 10, 11, 12, 17 &lt;223>/modified base = "2'-deoxy-25" fluorine corresponding nucleotide" &lt; 220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,6, 9,13,14,15,16, 18,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 173 uguucacugu ucaaaacgat t 21 -57- 152219 · Sequence Listing. Doc 201130494 &lt;210> 174 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;222>1, 4, 11,18 &lt;223>/modified base = "2^0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; moclified_base &lt;222> 21 &lt;223 〉/modified base==“5′·phosphorothioate thymidine” &lt;220〉 &lt;221&gt; modified_base &lt;222>2,3,5, 6, 7,8, 9,10, 12, 13, 14,15, &lt;223>/modified base = "2; -hydroxy corresponding nucleotide" &lt;400> 174 ucguuuugaa cagug Aacat t 21 &lt;210> 175 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; Modified_base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221> modified_base &lt;222>1, 3,4,5, 7, 8,10, 11, 12,17 &lt;223>/modified base = "2; -deoxy-25·fluorine corresponding nucleotide" •58· 152219·sequence table.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,6,9, 13,14,15,16,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 175 uguucacugu ucaaaacgat t 21

&lt;210&gt; 176 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222>1, 7, 11,18 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified base &lt;223&gt; Modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 3, 4,5,6,8,9, 10, 12,13, 14, &lt;223&gt;/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 176 ucguuuugaa cagugaacat t 21 &lt;210&gt; 177 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; Artificial sequence 59 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base Base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3,4, 5,7, 8,10, 11, 12, 17 &lt; 223>/modified base = "2'-deoxy-2' fluoride corresponding nucleotide" &lt;220〉 &lt;221〉 modified-base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 6, 9,13, 14,15, 16, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 177 uguucacugu ucaaaacgat t 21 &lt;210> 178 &lt;211 〉 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222>1, 2, 4,5, 6,7,11, 14, 18 &lt;223>/modified base = "2'-deoxy-2'·fluorine corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" -60- 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 8 , 9, 10, 12, 13, 15, 16, 17, 19 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 178 ucguuuugaa cagugaacat t 21 &lt;210&gt; 179 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence

&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' Phosphate group" &lt;220> &lt;221> modified_base &lt;222>2,3,4, 6,7, 9,10,11,16 &lt;223>/modified base = "2M3·曱 base Corresponding nucleotides &lt;220&gt;&lt;221> modified_base &lt;223&gt;/modified base == "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1 , 5, 8, 12, 13, 14, 15,17,18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 179 guucacuguu caaaacgaat t 21

&lt;210> 180 &lt;211&gt; 21 &lt;212&gt; DNA •61 · 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA ;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt;&lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5' · Phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;221>1,2, 3, 4,5, 6,7,8,9,10,11,13, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 180 uucguuuuga acagugaact t 21 &lt;210&gt; 181 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate Ester group" &lt;220〉 &lt;221〉 modified Base &lt;222>1,2,3,5, 6,8,9,10,15 -62- 152219-sequence table.doc 201130494 &lt;223>/modified base = "2'·0·曱 base Corresponding nucleotides &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;;222>4, 7,11,12, 13, 14, 16, 17,18, 19 &lt;223&gt; / modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 181 uucacuguuc aaaacgaagt t twenty one

&lt;210> 182 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;221〉 modified-base &lt;222> 13 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt ;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3,4,5, 6, 7,8, 9 , 10, 11, 12, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 182 -63- 152219 - Sequence Listing, doc 201130494 cuucguuuug aacagugaat t 21 &lt;210〉 183 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt ;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 4, 6, 13, 15, 16, 17,18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220〉 &lt;221> modified_base &lt;2 22>3, 5,7,8,9, 10, 11, 12, 14 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 183 ucauacgaag gauacuuuct t 21 &lt;210&gt; 184 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified_base -64-

】52219· Sequence Listing.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221&gt; modified-base &lt; 222> 6, 15 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base Base = "5' · phosphorothioate thymidine" &lt;220〉

&lt;221〉 modified_base &lt;222>1, 2,3, 4,5,7,8,9, 10, 11, 12, 13, &lt;223>/modified base = "2'-hydroxy corresponding core &lt;400&gt; 184 gaaaguaucc uucguaugat t 21 &lt;210&gt; 185 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: meaning of dsRNA Stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222 〉1,2,3,8,10,13, 16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222〉 21 &lt;223>/modified base = "5'·thiolate thymidine" -65- 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>4, 5, 6, 7, 9, 11, 12, 14, 15, 17, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 185 cccaggacau gauaauaagt t 21 &lt;210 〉 186 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; artificial sequence &lt;220&gt;&lt;223 Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lacking 5, phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 6,9 &lt;223&gt;/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,4,5, 7, 8,10,11 , 12,13,14, &lt;223>/modified base = "23-hydroxy corresponding nucleotide" &lt;400> 186 cuuauuauca uguccugggt t 21 &lt;210> 187 &lt;211> 22 &lt;212> DNA &lt;213&gt; 213 artificial sequence 66- 1522丨9-sequence table.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;220> &lt;221&gt; fflodified_base &lt;222&gt; 1 &lt ;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "5 '-0-methyl-thymidine>> &lt;220〉

&lt;221&gt; modified_base &lt;222>2,3,4,9,11,14,17 &lt;223>/modified base = "2'-0_methyl corresponding nucleotide" &lt;220〉 &lt;;221&gt; modified_base &lt;222&gt; 22 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>5, 6, 7 , 8, 10, 12, 13, 15, 16, 16, 19, <223> / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 187 tcccaggaca ugauaauaag tt 22 &lt;210> 188 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; , 3, 5,6,8,9 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" -67· 152219-sequence table.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 7,10, 11,12, 13,14,15,16, 17, 18, &lt;223>/modified base = "2'·hydroxyl "Nucleotide" &lt;400> 188 cuuauuauca uguccugggt t 21 &lt;210&gt; 189 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: dsRNA Sensed stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lacking 55-phosphate group" &lt;220&gt;&lt;221> modified_base &lt; 222>2, 3, 4,9, 15, 16, 19 &lt;223>/modified base = "2'-0.methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222 〉 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,5,6, 7, 8, 10, 11, 12, 13,14,17,18 &lt;223>/modified base = Γ2'-hydroxy corresponding nucleotide" &lt;400&gt; 189 guucaaaacg aagacuagct t 21 -68 - 152219 · Sequence Listing.doc 201130494 &lt; 210> 190 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence <220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221 &gt; modified-base &lt;222&gt; 3 &lt;223>/modified base = "2'-0-fluorenyl corresponding Nucleotide &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'_ phosphorothioate thymidine" &lt;220&gt;&lt;221〉 modified A base &lt;222>1,2,4,5,6,7,8,9, 10, 11, 12, 13, &lt;223>/modified base = "25-hydroxy corresponding nucleotide"

&lt;400> 190 gcuagucuuc guuuugaa.ct t 21 &lt;210> 191 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA stocks &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 •69- 152219-sequence table.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt; 220> &lt;221> modified-base &lt;222>2, 3,4,9, 15,16,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt ;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,5 ,6, 7,8,10,11, 12, 13, 14, 17,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 191 guucaaaacg aagacuagct t. 21 &lt;210&gt; 192 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222>3,6, 19 &lt;223>/modified base = "2 '·0· thiol corresponding nucleotides &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;;221〉 modified_base &lt;222>1, 2, 4,5,7, 8,9, 10, 11,12, 13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid &lt;400&gt; 192 70- 152219· Sequence Listing.doc 201130494 gcuagucuuc guuuugaact t 21 &lt;210&gt; 193 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220〉 &lt;223〉Artificial Description of the sequence: Sensed Shares of dsRNA &lt;220〉 &lt;221&gt; modified_base &lt;222〉 1

&lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>2,3,4, 9, 15,16, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5 '-Thiophosphoryl thymidine 』 &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 5, 6, 7, 8, 10, 11, 12, 13, 14, 17, &lt;223>/ Modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 193 guucaaaacg aagacuagct t 21 &lt;210&gt; 194 &lt;211&gt; 21 &lt;212> DNA <213> Artificial sequence &lt;220&gt;&lt;223 〉 Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_ba.se •71 · 152219-sequence table.doc 201130494 &lt;222>3,6, 15,19 &lt;223>/modified Base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'_ phosphorothioate thymidine &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2,4,5,7,8,9,10 11,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 194 gcuagucuuc guuuugaact t 21 &lt;210&gt; 195 &lt;211> 21 &lt;212&gt ; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "Nucleotide: Lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>2, 3,4, 9, 15, 16,19 &lt;223>/modified base = " 2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>1, 5, 6,7,8,10,11, 12,13,14,17, &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid - 72- 152219 - Sequence Listing.doc 201130494 &lt;400> 195 guucaaaacg aagacuagct t 21 &lt;210&gt; 196 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt; Description of the artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base

&lt;222>2,3,6, 7,8,9,10,12,13,14,15,19 &lt;223>/modified base = "2'-deoxy-oxime-fluorine corresponding nucleoside Acid &lt;220&gt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt;222&gt; 1,4,5,11, 16, 17,18 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 196 gcuagucuuc guuuugaact t 21

&lt;210&gt; 197 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220&gt; •73- 152219-sequence table.doc 201130494 &lt;221&gt; modified_base &lt;222〉 1 &lt;223>/modified base = "5'·0-mercapto-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3,4, 9,15, 16,19 &lt;;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'- Phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>5, 6, 7, 8, 10, 11, 12, 13,14,17, 18 &lt;223>/modified base == "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 197 tuucaaaacg aagacuagct t 21 &lt;210&gt; 198 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of the artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; mod Cated_ba.se &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221> modified-base &lt;222> 3 &lt; 223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt; / repaired; decorated base = "5' -thiophthalate thymidine"-74-

152219-Sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 4,5,6,7, 8, 9, 10, 11, 12, 13, &lt;223>/ Modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 198 gcuagucuuc guuuugaact t 21 &lt;210> 199 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' - Filling acid group" &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "5'-0.methyl-thymidine" &lt;220&gt;&lt; 221〉 modified-base ^ &lt;222&gt; 2, 3, 4, 9, 15, 16, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt;&lt;221&gt; modified_base &lt;222>5, 6,7,8 , 10,11,12, 13,14,17, 18 &lt;223>/modified base = "Γ·hydroxy corresponding nucleotide" &lt;400> 199 tuucaaaacg aagacuagct t 21 -75- 152219- Sequence Listing. Doc 201130494 &lt;210> 200 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222>3,6,19 &lt;223>/modified base = "25-0-thiol corresponding Nucleotide &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222 〉1,2, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 200 Gcuagucuuc guuuugaact t 21 &lt;210&gt; 201 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modifiedjbase &lt;222> 1 -76· 152219 List .doc 201130494 &lt;223>/modified base = "5'-0-methyl-thymidine" &lt;220> &lt;221> modified-base &lt;222>2,3,4,9,15 ,16,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified Base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221> modified_base

&lt;222>5,6,7,8, 10,11, 12,13, 14,17, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 201 tuucaaaacg Aagacuagct t 21 &lt;210&gt; 202 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;221> modified-base &lt;;222&gt; 3, 6, 15, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2,4,5, 7, 8,9, 10, 11 , 12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 202 77 152219 - Sequence Listing.doc 201130494 gcuagucuuc guuuugaact t 21 &lt;210> 203 &lt;211 〉 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/ Modified base == "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "5s-0-mercapto-thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3,4, 9, 15,16, 19 &lt;223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/ Modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>5, 6, 7, 8, 10, 11, 12, 13, 14, 17, 18 &lt;;223>/modified base = "2'. hydroxyl corresponding nucleotide" &lt;400> 203 tuucaaaacg aagacuagct t 21 &lt;210> 204 &lt;211&gt; 21 &lt;212> DNA &lt;213> artificial sequence 78 ·

152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;221&gt; modified_base &lt;222>2,3,6,7,8,9, 10,12,13,14,15,19 &lt;223>/modified base = "2'-deoxy-2' fluoride corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉

&lt;221&gt; modified_base &lt;222>1,4,5, 11, 16, 17, 18 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 204 gcuagucuuc guuuugaact t 21 &lt;210&gt; 20δ &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; Base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221> modified-base &lt;222&gt; 2, 3, 4, 9, 15, 16, 19 &lt;223>/modified base = "2'·deoxy-2'·fluorine corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" • 79· 152219-sequence table.doc 201130494 &lt;220> &lt;221> modified-base &lt;222>1, 5, 6 , 7, 8, 10, 11, 12, 13, 14, 17, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 205 guucaaaacg aagacuagct ΐ 21 &lt;210〉 206 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223 〉 Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt; 220> &lt;221&gt; modified_base &lt;222> 3 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 4, 5, 6, 7, 8,9, 10, 11, ] 2, 13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 206 gcuagucuuc guuuugaact ΐ 21 &lt;210&gt; 207 &lt;211> 21 &lt; 212> DNA &lt;213>Artificial sequence 80·1522丨9·Sequence list.doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221〉modified_ba.se&lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>2, 3, 4, 9, 15, 16,19 &lt;223>/modified base = "Γ-deoxy-2s·fluoro phase Should be nucleotides &lt;220〉

&lt;221〉 modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5: · phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 5, 6,7,8, 10, 11, 12,13,14,17, &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 207 guucaaaacg aagacuagct t 21 &lt;210〉 208 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 > Artificial Sequence &lt; 220 &lt; 223 &gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt; 220 &lt; 221 &gt; modified_base &lt; 222 &gt; 3, 6, 19 &lt; 223 > / modified base = "25-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 2, 4, 5, 7, 8,9,10, 11,12 , 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 208 gcuagucuuc guuuugaact t 21 &lt;210> 209 &lt;211> 21 &lt;212&gt; DNA &lt;;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: dsRNA Sensed stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;;222>2,3,4,9, 15, 16, 19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221〉 Modified_base &lt;222> 21 &lt;223>/modified base = "5'_ phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 5, 6, 7, 8, 10, 11,12,13,14, 17, 18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 209

Guucaaaaccg aagacuagct t 21 &lt;210> 210 &lt;211&gt; 21 &lt;212&gt; DNA 82-152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Reversal of dsRNA Stocks &lt;220&gt;&lt;221&gt; modified_base &lt;222>3,6,15,19 &lt;223&gt;/modified base == "2M&gt; methyl corresponding nucleotide" &lt;220> <221> Modified-base &lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine"

&lt;221&gt; modified_base &lt;222>1, 2,4, 5,7, 8,9,10, 11, 12,13, 14, &lt;223>/modified base = "2'-hydroxy corresponding core "Glycosylation" &lt;400> 210 gcuagucuuc guuuugaact t 21 &lt;210> 211 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence

&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphoric acid Ester group" &lt;220> <221> modified-base &lt;222>2,3,4,9, 15,16,19 &lt;223>/modified base = "2'-deoxy-2'- Fluorine-related nucleotides &lt;220> &lt;221> modified-base &lt;222&gt; 21 .83- 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "5'·phosphorothioate Thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 5, 6,7,8,10, 11,12, 13, 14,17, &lt;223>/modified base = "2 '·Hydroxyl corresponding nucleotides &lt;400&gt; 211 guucaaaacg aagacuagct ΐ 21 &lt;210> 212 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence : antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3,6,7,8, 9,10,12,13,14,15, &lt;223>/modified base = "Γ-deoxy-2' fluoride corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,4, 5, 11, 16, 17 , 18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 212 gcuagucuuc guuuugaact ΐ 21 &lt;210> 213 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA -84· 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Modified base = "nucleotide: lacking 55·phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 2, 4, 6, 8, 14, 17, 18 &lt;223>/modified base Base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine"

&lt;220〉 &lt;221&gt; modified_base &lt;222>1,3,5,7, 9, 10,11, 12,13,15, 16, &lt;223>/modified base = "2'-hydroxyl Corresponding nucleotides &lt;400&gt; 213 guauguauaa agauagccat t 21 &lt;210&gt; 214 &lt;211&gt; 21 &lt;212> DNA &lt;213&gt;

&lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220> &lt;221> modified_base &lt;222&gt; 5, 11, 13, 15, 17 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified-base • 85-152219·SEQ ID.doc 201130494 &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>1,2,3,4,6,7,8,9,10, 12,14,16,18, 19 &lt;223>/modified base = "2' -Hydroxy corresponding nucleotide" &lt;400> 214 uggcuaucuu uauacauact t 21 &lt;210> 215 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,3,4,7,8,16,1 7 &lt;223>/modified base == "25-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5 '-Thiophosphoryl thymidine 』 &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 5,6,9, 10, 11,12, 13, 14, 15,18, 19 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 215 cauugaccaa ggaaaucggt t 21 &lt;210> 216 • 86 -

152219· Sequence Listing.doc 201130494 &lt;211> 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; 221 &lt; 223 &gt; 223 &gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'·filling acid group" &lt;220〉

&lt;221&gt; modified_base &lt;222> 15 &lt;223&gt;/modified base = "2'-0-methyl corresponding nucleoside 睃" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5, 6, 7, 8, 9, 10 , 11, 12, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 216 ccgauuuccu uggucaaugt t 21

&lt;210> 217 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt; -87· 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222 〉1, 5, 6, 8,9,10, 12,13, 15 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;221〉 modified A base &lt;222> 21 &lt;223&gt; / modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3,4, 7,11 , 14,16, 17,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 217 caaacuauuu gucgcaggat t 21 &lt;210> 218 &lt;211> 21 &lt ;212>DNA&lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; Base = "nucleotide: lack of 5' phosphate group" &lt;220 &lt;221&gt; modified_base &lt;222> 9, 13 &lt;223&gt;/modified base = "2'-0-mercapto corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;;223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3,4,5, 6, 7,8,10 , 11, 12, 14, &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" • 88· 152219-sequence table_(1(^ 201130494 &lt;400> 218 uccugcgaca aauaguuugt t 21 &lt ;210> 219 &lt;211> 22 &lt;212> DNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;

&lt;221〉 modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221> modified-base &lt;222 〉 1 &lt;223〉/modified base = "5'-0-mercapto-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,6,7,9,10,11 , 13, 14, 16 &lt; 223 > / modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;223>/modified base = "5 '·Thionothioate thymidine>> &lt;220> &lt;221> modified-base &lt;222>4, 5,8,12,15, 17,18, 19,20 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 219 tcaaacuauu ugucgcagga tt 22

&lt;210> 220 &lt;211> 21 &lt;212&gt; DNA -89- 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA ;220&gt;&lt;221&gt; modified_base &lt;222>1,9,13,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 220 uccugcgaca aauaguuugt t 21 &lt;210&gt; 221 &lt; 211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt; 223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4,5, 6, 7, 8, 9 , 10,12,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide &lt;220&gt;&lt;221> modified_base &lt;222> 21 •90- 1522〗 9. Sequence Listing.doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt ; &lt;221&gt; modified_base &lt;222>1,11,13,14,15,16, 17,19 &lt;223>/modified base = "25_hydroxy corresponding nucleotide" &lt;400&gt; 221 acucucuccu Gugagaacat t 21 &lt;210〉 222 &lt;211〉 21

&lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>7,9 &lt;223>/modified base = "2'-0-methyl Corresponding nucleotides &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; Modified_base &lt;222>1, 2, 3,4, 5, 6, 8,10,11,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;;400&gt; 222 uguucucaca ggagagagut t 21 &lt;210> 223 &lt;211> 21 •91 - 152219·sequence table.doc 201130494 &lt;212> DNA &lt;213>artificial sequence &lt;220> &lt;223> artificial sequence Description: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221&gt; inodified_ba.se &lt;222>2,3, 4,5, 6,7,8,9, 10, 12, 18 &lt;223>/modified base = "2MD-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223 〉/modified base = "55· phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; raodified_ba.se &lt;222&gt; 1, 11, 13, 14, 15, 16, 17, 19 <223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 223 acucucuccu gugagaacat t 21 &lt;210> 224 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220〉 &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220〉 &lt;221〉 modified_base 92-

152219-Sequence List.doc 201130494 &lt;222>1,7, 9,19 &lt;223>/modified base = "2'-deoxy-25-fluoro corresponding nucleotide" &lt;220> &lt;221&gt;; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>2, 3, 4, 5, 6 , 8, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 224

Uguucucaca ggagagagut t 21 &lt;210> 225 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221&gt ; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt; 220> &lt;221> modified_base &lt;222>2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2'-0-mercaptonucleotide corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,11,13,14,15, 16, 17, 19 &lt ;223>/modified base = "2'. hydroxyl corresponding nucleotide" 93- 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 225 acucucuccu gugagaacat t 21 &lt;210&gt; 226 &lt;211> 21 &lt;212&gt ; DNA &lt; 213 > Artificial Sequence &lt; 220 > &lt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221> modified_base &lt;222>], 7, 9, 19 &lt;223> / Modified base = "2'-deoxy-2'_fluorine "Nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-thiolate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 226 uguucucaca ggagagagut t 21 &lt;210&gt; 227 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> •94- 152219·sequence table.doc 201130494 &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2^0-methyl corresponding nucleotide" &lt;220 〉 &lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1, 11, 13, 14, 15, 16, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" A &lt;400&gt; 227 acucucuccu gugagaacat t 21 &lt;210&gt; 228 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA ;220〉 &lt;221&gt; modified_base &lt;222〉 1

&lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>1, 7,9,19 &lt;223>/modified Base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "55 · phosphorothioate thymidine" &lt;220〉 &lt;221> modified_base &lt;222>2, 3,4,5,6, 8, 10, 11, 12, 13, 14,15,16,17,18 &lt;223>/modified base Base = "25 hydroxy corresponding nucleotide" 95- 152219 - Sequence Listing.doc 201130494 &lt;400> 228 uguucucaca ggagagagut t 21 &lt;210> 229 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence &lt;220〉 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of 5 '-Phosphate group> &lt;220> &lt;221> modified_base &lt;222>2,3,4,5,6,7,8, 9,10, 12, 18 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222> 21 &l t;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>1, 11, 13, 14, 15, 16, 17,19 &lt;;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 229 acucucuccu gugagaacat t 21 &lt;210&gt; 230 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence&lt;213&gt;;220>&lt;223> Description of artificial sequence: antisense stock of dsRNA • 96· 152219 - sequence listing. doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 7,9,19 &lt;223 〉/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'- Thiophthalate thymidine "220220" &lt;221&gt; modified__base &lt;222>2, 3,4, 5,6,8,10, 11,12,13,14, 15, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide"

Uguucucaca ggagagagut t 21 &lt;210&gt; 231 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5s-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4 , 5,6, 7, 8, 9, 10,12,18 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,11, 13, 14, 15,16,17 , 19 -97- 152219 · Sequence Listing.doc 201130494 &lt;223〉/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 231 acucucuccu gugagaacat t 21 &lt;210> 232 &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223&gt; / Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1, 3, 7,9, 19 &lt;223>/modified Base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221&gt; mod Iified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 4, 5, 6, 8, 10, 11,12,13,14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 232 uguucucaca ggagagagut t 21 &lt;210> 233 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA • 98· 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221〉 modified— Base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;(221&gt; modified-base &lt;222>2, 3, 4, 5 , 6,7, 8,9, 10,12, 18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222〉 21 &lt;223>/modified base = "5'-phosphorothioate thymidine"

&lt;221&gt; modified_base &lt;222>1,11,13,14, 15, 16,17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 233 acucucuccu Gugagaacat t 21 &lt;210&gt; 234 &lt;211> 21 &lt;212&gt; DNA &lt;213> artificial sequence

&lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222>1,3,7,9, 19 &lt;223>/modified base Base = "2'-deoxy-2'·fluoro corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-thio &lt;220&gt;&lt;221> modified_base •99- 152219-sequence table.doc 201130494 &lt;222>2, 4, 5, 6, 8, 10,11,12, 13, 14, 15 , 16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 234 uguucucaca ggagagagut t 21 &lt;210> 235 &lt;211&gt; 21 &lt;212> DNA &lt;213 〉Artifical sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: Lack of V-phosphate group" &lt;220> &lt;221> modified-base &lt;222>2,3,4,5,6, 7,8, 9,10, 12,18 &lt;223>/modified Base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,11, 13, 14, 15,16,17, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 235 acucucuccu gugagaacat t 21 &lt;210&gt; 236 &lt;211> 21 &lt;212> DNA &lt;213&gt; Sequence &lt;220> -100- 152219 · Sequence Listing.doc 201130494 &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified Base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3, 7, 9,19 &lt;223>/modified base = " 2'-0-methyl corresponding nucleotide" &lt;220〉

&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 4, 5, 6, 8, 10, 11, 12,13, 14, 15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 236 uguucucaca ggagagagut t 21 &lt ;210&gt; 237 &lt;211> 21 &lt;212> DNA <213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7, 8,9, 10, 12,18 &lt;223>/modified base = "2'_0-methyl corresponding nucleotide" &lt;220> -101 - 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,11,13, 14, 15, 16 ,17, 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 237 Acucucuccu gugagaacat t 21 &lt;210&gt; 238 &lt;211> 21 &lt;212> DMA &lt; 213 &gt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: antisense stock of dsRNA &lt;220 &lt; 221 &gt;; modified_base &lt;222>1,3,7,9,19 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 4, 5, 6, 8, 10, 11, 12,13, 14,15,16, 17,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 238 uguucucaca ggagagagut ΐ 21 &lt;210&gt; 239 &lt;211 〉 21 &lt;212> DNA &lt;213> artificial sequence 102·

152219-Sequence List.doc 201130494 &lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 <223> / Modified Base = "Nuclear Glycoside: lack of V-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "5'·0·methyl·thymidine" &lt;220〉

&lt;221&gt; modified_base &lt;222>2, 3,4,5, 6,7,8,9,10, 12,18 &lt;223>/modified base = "2'-0· thiol corresponding nucleus "Glycosylation" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222 〉11, 13,14,15,16, 17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 239 tcucucuccu guga.gaa.cat t 21 &lt;210&gt 240 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base <222&gt; 7,9,19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" -103 - 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt;modified_b&se&lt;222>2, 3, 4, 5, 6, 8,10, 11,12, 13, 14, &lt;223>/modified base == "2'-hydroxy corresponding nucleotide &lt;400&gt; 240 uguucucaca ggagagagut t 21 &lt;210&gt; 241 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt; 220> &lt;221> modified_base &lt;222&gt; 1 &lt; 223>/modified base = "5:-0. methyl-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4, 5, 6,7, 8,9, 10 , 12, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified Base = "5^ phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>11, 13,14,15, 16,17,19 • 104 152219-sequence table.doc 201130494 &lt; 223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 241 tcucucuccu gugagaacat t 21 &lt;210> 242 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt; 220> &lt;223> Description of artificial sequence: the inverse of dsRNA Right stock

&lt;220&gt;&lt;221> modified-base &lt;222>1,3,4,5,6,7, 9,19 &lt;223>/modified base = "25-deoxyfluorinated nucleotide &lt;220〉 &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222 〉2, 8,10,11, 12, 13, 14, 15,16, 17,18 &lt;223>/modified base = "Γ-hydroxy corresponding nucleotide" &lt;400&gt; 242 uguucucaca ggagagagut t 21 &lt;210&gt; 243 &lt;211&gt; 21 &lt;212&gt;212&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA&lt;220&gt;&lt;221&gt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate ester group" -105- 152219-sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 2, 3, 4,5, 6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2'·deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt ; &lt;221&gt; raodified_ba.se &lt;222> 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>1,11, 13, 14,15,16,17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 243 acucucuccu gugagaacat t 21 &lt;210&gt; 244 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt;223 Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,7, 9,19 &lt;223&gt;/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221&gt; Modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3, 4,5, 6,8,10, 11, 12, 13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 244 uguucucaca ggagagagut t 21 •106. 152219-SEQ ID NO. .doc 201130494 &lt;210&gt; 245 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt; Modified_base &lt;222&gt; 1 &lt;223>/modified base Base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221〉 modified-base &lt;222>2, 3, 4, 5,6,7, 8,9, 10, 12,18 &lt;223>/经Ί饰基==“2'·去Oxygen-2'·fluoro corresponding nucleotide &lt;220&gt;&lt;221>modified_ba.se&lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt; 220> &lt;221&gt; modified_base &lt;222>1, 11, 13,14,15,16,17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 245 acucucuccu gugagaacat t 21 &lt;210&gt; 246 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; 221〉 modified-base &lt;222>1, 3,4, 5, 6, 7,9,19-107- 152219-sequence table_doc 201130494 &lt;223>/modified base = "2s•deoxygen- 2'-Fluor corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,8,10, 11,12,13,14, 15,16,17, 18 &lt;223>/modified base = " 2:·hydroxy corresponding nucleotide” &lt;400&gt; 246 uguucucaca ggagagagut t 21 &lt;210> 247 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220&gt;&lt;223&gt; Description: Sensed Shares of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 5, 6, 9, 12, 14,16,17,18, 19 &lt;223>/modified base = "2:-0-methyl corresponding core "Glycolic acid" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5:-thiophthalate thymidine" &lt;220&gt;221&gt; modified_base &lt; 222>4, 7, 8, 10,11, 13,15 &lt;223>/modified base = "2:·hydroxy corresponding nucleotide" &lt;400&gt; 247 -108- 152219 · Sequence Listing.doc 201130494 Uuuauugaca auacgcuuut t 21 &lt;210> 248 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222〉 1

&lt;223>/modified base = "nucleotide: lack of 5'-acid sulfhydryl group" &lt;220> &lt;221&gt; modified_base &lt;222>7, 13,16 &lt;223>/modified base Base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉 &lt;221〉 modified-base &lt;222>1,2,3,4,5,6,8,9,10,11,12,14, &lt;223>/modified base = " 2'·hydroxyl-related nucleotides &lt;400&gt; 248 aaagcguauu gucaauaaat t 21 &lt;210> 249 &lt;211> 21 &lt;212> DNA &lt;213>artificial sequence &lt;220> &lt;223> artificial sequence Description: Sensed strands of dsRNA &lt;220&gt;&lt;221> modified-base •109- 152219-sequence table.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nucleotide: missing 5 '·phosphate group> &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2,3, 4,5,6,7, 8,9, 11,14,18,19 &lt;223>/ Modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; rnodified_base &lt;222>10, 12, 13, 15, 16, 17 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 249 cuuccucucg caacaaacut t 21 &lt;210&gt; 250 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphate group &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1 · 19 &lt;223>/modified base = "2' · hydroxyl corresponding nucleotide" • 110·

152219· Sequence Listing.doc 201130494 &lt;400&gt; 250 aguuuguugc gagaggaagt t 21 &lt;210&gt; 251 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Sense stock of dsRNA &lt;220〉

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3,4, 6,8,9,10,12,13,15,19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222 〉 21 &lt;223〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,5, 7, 11, 14, 16, 17, 18 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400&gt; 251 gaccauauuu auuauaagut t 21 &lt;210> 252 &lt;211> 21 &lt;212&gt; DNA <213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; -111 - 152219_ Sequence Listing.doc 201130494 &lt;221> modified_base &lt;222> 1 &lt;223>/modified Base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>4, 6,9,13 &lt;223>/modified base = "2'- 0·methyl corresponding nucleotide” &lt;220〉 &lt;221&gt; modifi Ed_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 2, 3, 5, 7, 8, 10,11, 12,14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 252 acuuauaaua aauaugguct t 21 &lt;210> 253 &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt; / Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 4,5, 13, 14,17,18, 19 &lt;223 〉/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-thio Phosphate thymidine" -112- 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 6,7,8,9, 10,11,12, 15,16 &lt;;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 253 ugaccaagga aaucgg Ccut t 21 &lt;210&gt; 254 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt;

&lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: absent 55-phosphate group &lt;220> &lt;221&gt; modified_base &lt;222> 18 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221 〉 modified-base &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3, 4,5, 6, 7,8, 9, 10, 11,12, &lt;223>/modified base = "2'_hydroxy corresponding nucleotide" &lt;400&gt; 254

Aggccgauuu ccuuggucat t 21 &lt;210&gt; 255 &lt;211> 21 &lt;212> DNA 113-152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: DsRNA Stocks &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt; 222>1,4,5,13,14, 17, 18,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified one Base &lt;222> 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 6, 7, 8 , 9, 10, 11, 12, 15, 16 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 255 ugaccaagga aaucggccut t 21 &lt;210> 256 &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222>8,18 &lt;223&gt; / Modified base = "2'·0· thiol corresponding Nucleotide &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 •114· 152219·sequence table.doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;;220〉&lt;221〉 modified-base &lt;222>1, 2, 3,4,5,6,7,9, 10, 11, 12,13, &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&lt;400&gt; 256 aggccgauuu ccuuggucat t 21

&lt;210&gt; 257 &lt;211&gt; 21 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1, 4,5,13, 14 , 17, 18, 19 &lt; 223 > / modified base = "2' · 0 · thiol corresponding nucleotide" &lt; 220 > &lt; 221 > modified a base &lt; 222 > 21 &lt; 223 > / Modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,3,6, 7,8,9,10, 11,12,15 , 16 &lt; 223 > / modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 257 ugaccaagga aaucggccut t 21 &lt;210&gt; 258 &lt;211> 21 115- 152219-sequence table.doc 201130494 &lt;;212>DNA&lt;213>Artificialsequence&lt;220>&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222>14,18 &lt;223&gt; Modified base = "2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 4,5, 6, 7,8, 9, 10, 11, 12, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 258 aggccgauuu ccuuggucat t 21 &lt;210&gt ; 259 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222&gt;; 1 &lt;223>/modified base = "nucleotide: lack of 5' decanoate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,4,5,13, 14,17 , 18, 19 &lt; 223 > / modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified base • 116- 152219 - Sequence Listing.doc 201130494 &lt;222 〉 21 &lt;223〉/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3, 6, 7, 8,9,10, 11, 12,15, 16 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400 &gt; 259 ugaccaagga aaucggccut t 21

&lt;210&gt; 260 &lt;211&gt; 21 &lt;212> DNA <213>Artificial sequence &lt;220> <223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 4, 5, 8, 9,10,11, 12, 13,14, 17, 18 &lt;223>/modified base = "2'-deoxy-2'·fluoro corresponding nucleotide" &lt;220&gt ; &lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine"

&lt;221&gt; modified_base &lt;222>1,2,3, 6,7,15,16,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 260 aggccgauuu Ccuuggucat t 21 &lt;210> 261 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;220> 117- 152219-sequence table.doc 201130494 &lt;223> Description of artificial sequence: meaning of dsRNA Stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;;222&gt; 1 &lt;223>/modified base = "5'·0·decyl-thymidine" &lt;220> &lt;221&gt; modified_base

<222> 2,4,5,13,Η 17,18,19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified— Base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>3, 6, 7, 8, 9, 10, 11, 12, 15, 16 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 261 tgaccaagga aaucggccut t 21

&lt;210&gt; 262 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> -118- 152219 · Sequence Listing.doc 201130494 &lt;221> modified-base &lt;222 〉 18 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = " 5'-thiolate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,2,3, 4, 5, 6, 7,8, 9, 10, 11,12, 13, 14,15,16, 17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400&gt; 262 aggccgauuu ccuuggucat t 21 &lt;210&gt; 263 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-decarboxylate group" &lt;220> &lt;221> modified-base &lt;222 〉 1 &lt;223〉/modified base = "5'-0-methyl-thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 4, 5, 13, 14, 17 , 18,19 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-Thiophosphate thymidine" -119- 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>3, 6,7, 8, 9, 10,11,12 , 15, 16 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400> 263 tgaccaagga aaucggccut t 21 &lt;210> 264 &lt;211> 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence·· dsRNA Antisense stock &lt;220> &lt;221&gt; modified_base &lt;222>8,18 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220&gt;&lt;221 〉 modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 4,5 , 6,7, 9, 10,11, 12, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 264 aggccgauuu ccuuggucat t 21 &lt;210&gt; 265 &lt;211&gt 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strands of dsRNA • 120 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 55-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base Base = "5'-0-mercapto-thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 4, 5, 13, 14, 17, 18, 19 &lt;223>/ Modified base = "2'-0·methyl corresponding nucleotide"

&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>3,6, 7, 8,9, 10, 11,12,15,16 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 265 tgaccaagga aaucggccut t 21

&lt;210&gt; 266 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; 223 &gt; 223 &gt; 223 &gt; 223 &gt; 223 > Description of the artificial sequence: antisense stock of dsRNA &lt;220 &lt;221 &lt; 221 &gt; modified_base &lt; 222> 14, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 -121 - 152219 List .doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1,2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 266 aggccgauuu ccuuggucat t 21 &lt;210&gt; 267 &lt;211 〉 21 &lt;212> DNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "5'·0·methyl -thymidine" &lt;220&gt;&lt;221〉 modified a base &lt;2 22>2, 4,5,13, 14, 17, 18,19 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5:-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3,6,7, 8, 9, 10, 11, 12, 15, 16 &lt; 223 > / modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 267 -122- 152219 · Sequence Listing.doc 201130494 tgaccaagga aaucggccut t 21 &lt;210&gt; 268 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base

&lt;222>4,5,8,9, 10,11,12, 13, 14,17, 18 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide &lt;220&gt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_b£Lse &lt;222 〉1,2,3, 6,7, 15, 16,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 268 aggccgauuu ccuuggucat t 21 &lt;210&gt; 269 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221&gt; modified_base -123 - 152219-sequence table.doc 201130494 &lt;222>1, 4, 5 , 13,14, 17,18, 19 &lt;223>/modified base = "2'-degassing-2'·fluorine corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222&gt 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modifi Ed-base &lt;222>2,3,6,7,8,9,10, 11, 12, 15,16 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 269 ugaccaagga aaucggccut t 21 &lt;210&gt; 270 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt;223 Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 18 &lt;223 〉/modified base==“2′-0-methyl corresponding nucleotide” &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-sulfur Phosphate thymidine" &lt;220&gt;&lt;221> modified_base &lt;221>1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, &lt;223>/modified Base == "2'·hydroxyl corresponding nucleotide" -124- 152219 - Sequence Listing.doc 201130494 &lt;400> 270 aggccgauuu ccuuggucat t 21 &lt;210&gt; 271 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: dsRNA Sense Unit &lt; 220>

&lt;221&gt; modified_ba.se &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>1, 4,5,13, 14, 17, 18,19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 6,7,8,9, 10 , 11, 12, 15, 16 &lt; 223 > / modified test base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 271 ugaccaagga aaucggccut t 21 &lt;210> 272 &lt;211&gt; 21 &lt;212&gt ; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> -125- 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>8 , 18 &lt; 223 > / modified base = "2'-0 · methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = " 5'-Thiophosphate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt; 222>1,2,3,4,5,6,7, 9,10, 11,12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 272 aggccgauuu ccuuggucat t 21 &lt;210&gt; 273 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modificd_base &lt;222>1, 4, 5, 13,14, 17, 18, 19 &lt;223>/modified base = "2'-deoxy-2'_fluorine corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt ;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3, 6, 7, 8, 9, 10, 11, 12 ,15,16 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" -126 152219-Sequence table_€1〇〇201130494 &lt;400&gt; 273 ugaccaagga aaucggccut t 21 &lt;210&gt; 274 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of the sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified-base • &lt;222>14,18 &lt;223&gt;/modified base = "2'-0-methyl corresponding nucleotide &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified-base &lt;;222>1, 2, 3,4,5, 6, 7,8,9, 10,11,12, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 274

Aggccgauuu ccuuggucat t 21 &lt;210&gt; 275 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;; modified a base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 55_phosphate group" • 127 · 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified —base &lt;222>1, 4,5,13,14,17, 18, 19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220 〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,3, 6 , 7, 8, 9,10,11, 12, 15, 16 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 275 ugaccaagga aaucggccut t 21 &lt;210&gt; 276 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 5 , 8, 9, 10,11,12,13,14, 17,18 &lt;22 3>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5 '·Thionothioate thymidine” &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3,6,7, 15,16,19 &lt;223>/modified base = "2' ·Hydroxyl corresponding nucleotides" &lt;400> 276 aggccgauuu ccuuggucat t 21 -128·

152219-Sequence List.doc 201130494 &lt;210> 277 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221〉 modified-base &lt;222>1, 2,7, 13,14, 17,18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt ; &lt;221〉 modified_base &lt;222&gt; 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3,4, 5, 6,8, 9, 10,11, 12,15, 16,19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 277 ucaaaacgaa gacuagcuat t 21 &lt;210> 278 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified_base &lt;222&gt; 223>/modified base = "nucleotide · lacking 55-phosphate group" -129- 152219-sequence table.doc 201130494 &lt;220> &lt;221> modified_base &lt;222>1,5 &lt;223 〉/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-thio Phosphate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>2,3,4, 6, 7, 8, 9, 10, 11, 12, 13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 278 uagcuagucu ucguuuugat t 21 &lt;210> 279 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>4, 5, 6, 7, 8, 10, 11, 13, 15 &lt;223>/modified base = "25-0·thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5' - phosphorothioate thymidine" &lt;220> &lt;221> modified-base-130-152219·sequence table.doc 201130494 &lt;222>1,2, 3,9,12, 14, 16,17,18 , 19 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400&gt; 279 gaaucuucau cauacgaagt t 21 &lt;210> 280 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 6 &lt ;223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5 ^Thiophosphoryl thymidine"

&lt;220〉 &lt;221〉 modified-base &lt;222>1,2,3,4,5,7,8,9,10,11,12, 13, &lt;223>/modified base = " 2'-hydroxy corresponding nucleotide" &lt;400> 280 cuucguauga ugaagauuct t 21 &lt;210> 281 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213> artificial sequence &lt;220&gt; 131 · 152219 · Sequence Listing. Doc 201130494 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate Ester group &lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 5,6, 7, 8,10,11, 13, 5 &lt;223>/modified base = "2'-0- Methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; Modified-base &lt;222>1,2,3, 9,12, 14, 16, 17, 18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 281 gaaucuucau cauacgaagt t 21 &lt;210&gt; 282 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt;&lt;220>&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222>1, 2, 6, 19 &lt;223&gt;/modified base = "2 '-0-thiol corresponding nucleotides &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt; 220> -132· 152219·Listing list.doc 201130494 &lt;221&gt; modified_base &lt;222>3,4,5, 7,8,9,10,11,12,13,14,15, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 282 cuucguauga ugaagauuct t 21 &lt;210&gt; 283 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;220> 0 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphoric acid Ester group &lt;220> &lt;221> modified-base &lt;222>4,5,6,7,8,10,11,13,15 &lt;223>/modified base = "2'-0 - thiol corresponding nucleotide" &lt;220&gt;&lt;221> modified a base

&lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1,2,3, 9, 12 , 14,16,17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 283 gaaucuucau cauacgaagt t 21 &lt;210&gt; 284 &lt;211&gt; 21 &lt;;212>DNA&lt;213>Artificial sequence 133- 152219-Sequence table.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1,2,6, 18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt; 223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 3, 4, 5, lt 8, 9, 10, 11, 12, 13 , 14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 284 cuucguauga ugaagauuct t 21 &lt;210&gt; 285 &lt;211&gt; 21 &lt;212&gt; DNA &lt;;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &Lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 4,5, 6, 7, 8,10, 11, 13, 15 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified one Base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" • 134-1522〗 9-sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt; 222>1,2,3,9,12, 14,16, 17,18,19 &lt;223>/modified base = "25. hydroxyl corresponding nucleotide" &lt;400&gt; 285 gaaucuucau ca.ua. Cgaa.gt t 21 &lt;210&gt; 286 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt;

&lt;220〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222>1, 2, 3,4,6,8, 11,17,18 , 19 &lt; 223 > / modified base = "2'-deoxy-2' · fluorine corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base • &lt;222>5,7,9, 10,12, 13,14, 15,16 &lt;223>/ Modified base = "2'_hydroxy corresponding nucleotide" &lt;400&gt; 286 cuucguauga ugaagauuct t 21 &lt;210&gt; 287 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt; -135- 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide : lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "5'-0·decyl-thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>2,4,5, 6, 7, 8,10, 11,13, 1 5 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5 '·Thionothioate thymidine” &lt;220&gt;&lt;221&gt; modified_base &lt;222>3,9,12, 14, 16, 17,18,19 &lt;223>/modified base = "2' "Hydroxyl corresponding nucleotide" &lt;400> 287 taaucuucau cauacgaagt t 21 &lt;210&gt; 288 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; Modified_base &lt;222&gt; 6 &lt;223>/modified base = "2M> thiol corresponding nucleotide" • 136-

152219-Sequence List.doc 201130494 &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> Modified-base &lt;222>1,2,3,4, 5, 7, 8, 9,10, 11,12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400&gt; 288 cuucguauga ugaagauuct t 21

&lt;210> 289 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base φ &lt;222&gt; 1 &lt;223>/modified base = "5'-0-methyl-thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,4,5,6,7, 8, 10,11,13,15 &lt;223 〉/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·thio Phosphate thymidine" &lt;220> &lt;221> modified_base -137- 152219 · Sequence Listing.doc 201130494 &lt;222>3,9, 12, 14, 16, 17,18,19 &lt;223>/modified Base = "2'-hydroxyl corresponding nucleotide" &lt;400> 289 taaucuucau cauacgaagt t 21 &lt;210> 290 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 〉 Description of artificial sequence: antisense stock of dsRNA &lt;220〉 &lt;221&gt; modifie D_base &lt;222>1,2,6,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>3,4,5,7, 8, 9,10 , 11,12, 13, 14, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 290 cuucguauga ugaagauuct t 21 &lt;210&gt; 291 &lt;211> 21 &lt;212 〉 DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222> 1 •138 152219 · Sequence Listing.doc 201130494 &lt;;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "5 '·0·曱基·thymidine>> &lt;220〉 &lt;221&gt; modified^base &lt;222>2, 4,5,6,7,8,10,11, 13,15 &lt;223>/ Modified base = "2'-0. thiol corresponding nucleotide" &lt;220〉

&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>3, 9, 12,14,16,17,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 291 taaucuucau cauacgaagt t 21 &lt;210> 292 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221>modified_ba.se &lt;222>1, 2, 6, 18,19 &lt;223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220> • 139- 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>3,4,5, 7, 8, 9,10, 11,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 292 cuucguauga ugaagauuct t 21 &lt;210> 293 &lt;211&gt; 21 &lt;212 〉 DNA &lt; 213 > artificial sequence &lt; 220 > &lt; 223 > description of artificial sequence : Sense of stranded strands of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220> &lt;221&gt; Modified-base &lt;222> 1 &lt;223>/modified base = "5MD·methyl-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 4, 5, 6,7, 8, 10, 11, 13,15 &lt;223>/modified base == "2'-(&gt;methyl corresponding nucleotide" &lt;220> &lt;221 &gt; modified_ba.se &lt;222〉 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3,9, 12, 14, 16, 17, 18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 293 taaucuucau cauacgaagt t 21 -140- 152219 · Sequence Listing.doc 201130494 &lt;210> 294 &lt;211&gt; 21 &lt;;212> DMA &lt; 213 > artificial sequence &lt; 220 > &lt; 223 > description of artificial sequence: antisense stock of dsRNA &lt; 220 &lt; 221 > modified_ba.se &lt; 222 > 1, 2, '3, 4,6,8, 11, 17, 18,19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleoside "&Lt; 220>

<221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>5,7,9 , 10, 12, 13, 14,15, 16 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 294 cuucguauga ugaagauuct t 21 &lt;210&gt; 295 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223&gt; Modified base = "nucleotide: lack of 55-filler group" &lt;220> &lt;221&gt; modified_base &lt;222>4,5, 6,7,8, 10, 11, 13,15 &lt;223 〉/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" -141 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3,9, 12,14, 16,17, 18,19 &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 295 gaa Ucuucau cauacgaagt t 21 &lt;210> 296 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221 〉 modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 6 &lt;223&gt; / Modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-thiophosphoric acid Ester thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3, 4,5, 7, 8, 9, 10,11, 12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 296 cuucguauga ugaagauuct t 21 -142· 152219 - Sequence Listing.doc 201130494 &lt;210> 297 &lt;211&gt; 21 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: Lack of 5'-phosphate group" &lt;220 &lt;221&gt; modified_base &lt;222>4,5,6, 7, 8, 10, 11,13,15 &lt;223>/modified base = "2'-deoxy-2'·fluoro corresponding nucleoside Acid &lt;220〉 &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified a base &lt;222>1, 2,3, 9, 12, 14,16,17, 18, 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide"

&lt;400&gt; 297 gaaucuucau cauacgaagt t 21 &lt;210&gt; 298 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222>1, 2, 6, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" • 143· 152219 · Sequence Listing. 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 3, 4,5, 7, 8, 9, 10, 11,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 298 cuucguauga ugaagauuct t 21 &lt;210&gt; 299 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA&lt;220&gt;&lt;221&gt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>4, 5, 6, 7, 8, 10,11,13, 15 &lt;223>/modified base = " 2'-Deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉 &lt;221〉 modified-base &lt;222>1, 2, 3,9,12, 14, 16, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding Nucleotide &lt;400> 299 gaaiicuucau cauacgaagt t 21 144- 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 300 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt; 〉 Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221〉 modified_base &lt;222>1,2, 6,18, 19 &lt;223>/modified base = "2'-0- Base corresponding nucleotide" &lt;220〉

&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>3,4, 5,7,8, 9,10,11,12,13,14,15,16,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 300 cuucguauga ugaagauuct t 21 &lt;210> 301 I &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4,5, 6, 7, 8,10, 11, 13,15 •145- 152219-sequence table.doc 201130494 &lt;223>/modified base = "2'·degassing-2'·fluorine corresponding nucleotide" &lt;220〉 &lt;;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 9 ,12, 14, 16,17, 18,19 &lt;223>/modified base = "25·hydroxyl phase Nucleotide "&lt; 400 &gt; 301 gaaucuucau cauacgaagt t 21

&lt;210> 302 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modificd_base &lt; 222>1, 2, 3, 4, 6, 8, 11, 17, 18, 19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt ; &lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>5 , 7, 9, 10, 12, 13, 14, 15, 16 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 302 cuucguauga ugaagauuct t 21 &lt;210&gt; 303 &lt;211〉 21 146-

152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;&lt;223&gt;/modified base = "nucleotide: lack of 5'-lucate group" &lt;220&gt;&lt;221> modified-base &lt;222>5,9, 10,11,13,16 , 18, 19

&lt;223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base == "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 6, 7, 8, 12, 14, 15, 17 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 303 gggauagauc uauaauguut t 21 &lt;210> 304 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of cadaveric-phosphate group" &lt;;220&gt;&lt;221&gt; modifiedbase • 147· 152219-sequence table.doc 201130494 &lt;222>3,6,8, 14 &lt;223>/modified base = "2'-0-methyl corresponding nucleoside Acid &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1,2, 4, 5, 7, 9,10, 11, 12,13, 15, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 304 aacauuauag aucuauccct t 21 &lt;210&gt; 305 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group &lt;220〉 &lt;221> modified_base &lt;222>1,2, 4,5,6, 8,9,11, 17 &lt;223>/modified base = "2'·0-methyl corresponding Nucleotide &lt;220> <221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-thiolate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3,7,10, 12, 13, 14, 15, 16,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -148- 152219-SEQ ID NO. .doc 201130494 &lt;400&gt; 305 cuauuugucg caggaauaat t 21 &lt;210&gt; 306 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220 &lt;223&gt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide·lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,13, 17 &lt;223>/modified base = "2M> thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5' - phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base • &lt;222>1,3, 4,5,6,7,8,9, 10,11,12,14, &lt; 223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 306 uuauuccugc gacaaauagt t 21 &lt;210&gt; 307 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence &lt; 220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> • 149· 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5, phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,2,3,5,6,7,13,15,18, 19 &lt;223> / Modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;22 1> modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>4,8, 9, 10,11, 12, 14,16, 17 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 307 ucuauuugaa gauaugacut t 21 &lt;210&gt; 308 &lt; 211 &gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; / Modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>4, 6,12, 16 &lt;223>/modified base Base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate chest Glycoside" -150-

152219-Sequence table.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 5, 7,8, 9, 10, 11,13,14,15, &lt;223>/ Modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 308 agucauaucu ucaaauagat t 21 &lt;210&gt; 309 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence • &lt;220&gt;;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220〉 &lt;221&gt; modified__base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1,2,3,5, 6,7, 13, 15, 18, 19 &lt;223>/modified base = "2'·0· Sulfhydryl corresponding nucleotides &lt;220〉

&lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>4, 8, 9,10,11, 12,14, 16,17 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 309

Ucuauuugaa gauaugacut t 21 &lt;210&gt; 310 &lt;211&gt; 21 &lt;212>.DNA 151 · 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: dsRNA Antisense stock &lt;220> &lt;221&gt; modified_base &lt;222>4,6,10,12,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3 , 5, 7, 8,9, 11, 13, 14,15, 17, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 310 agucauaucu ucaaauagat t 21 &lt;210&gt; 311 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 <223> / Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2,3, 5, 6, 7,13, 15, 18, 19 &lt;223>/modified base = 2'-〇-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 -152- 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "5'- Phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 8, 9,10,11, 12,14, 16,17 &lt;223>/modified base = "2' -hydroxy corresponding nucleotide" &lt;400&gt; 311 ucuauuugaa gauaugacut t 21

&lt;210&gt; 312 &lt;211> 21 &lt;212&gt; DNA

&lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221> modified-base &lt;222>3,4, 6, 8, 9, 10 , 11, 12, 16 &lt; 223 > / modified base = "2' · deoxy-2' · fluorine corresponding nucleotide" &lt; 220 > &lt; 221 > modified_base &lt; 222 > 21 &lt; 223 > / Modified base = "5'-thiolate thymidine"

&lt;221&gt; modified_base &lt;222>1,2, 5, 7,13,14,15,17,18,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 312 agucauaucu ucaaauagat t 21 &lt;210> 313 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA's stocks • 153· 152219 · Sequence Listing.doc 201130494 &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "55-0. thiol-thymidine" &lt;220&gt;&lt;221&gt; raodified_ba.se &lt;222>2, 3, 5, 6,7, 13, 15, 18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; inodified_base &lt;222>4,8,9,10,11, 12, 14, 16, 17 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 313 tcuau Uugaa gauaugacut t 21 &lt;210> 314 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221 〉 modified-base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221&gt; modified_base •154-

152219-Sequence List.doc 201130494 &lt;222>4, 6, 12,16 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base == "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 5, 7, 8, 9,10,11,13,14,15,17,18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 314

Agucauaucu ucaaauagat t 21 &lt;210&gt; 315 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "5'-0.methyl-thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,5,6,7, 13, 15, 18,19 &lt;223&gt; / Modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·thiophosphoric acid Ester thymidine" -155- 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>4, 8, 9,10,11,12,14, 16, 17 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 315 tcuauuugaa gauaugacut t 21 &lt;210&gt; 316 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222>4,6, 10, 12, 16 &lt;223>/modified base = "2Μ&gt; methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 5,7,8, 9, 11, 13, 14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 316 agucauaucu ucaaauagat t 21 &lt;210&gt; 317 &lt;211> 21 &lt;;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA&lt;220&gt; -156 152219. Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = mercapto group ·Thymidine" &lt;220> &lt;221> modified-base &lt;222>2,3,5,6, 7,13,15, 18,19 &lt;223>/modified base = "2'- 0·thiol corresponding nucleotide

&lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "cadastane thiodecanoate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;4,8,9, 10,11,12, 14,16,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 317 tcuauuugaa gauaugacut t 21 &lt;210> 318 • &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;2> modified-base &lt;222>3, 4,6 , 8, 9, 10, 11, 12, 16 &lt; 223 > / modified base = "2'-deoxy-2 ^ fluorine corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222〉 21 &lt;223>/modified base = "5'-thiophthalate thymidine" -157- 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified_base &lt;222>1,2, 5, 7, 13,14,15, 17, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 318 agucauaucu ucaaauagat t 21 &lt;210> 319 &lt ;211> 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223>People Description of sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221〉modified_ba.se&lt;222>1, 2,3,5,6,7,13, 15,18, 19 &lt;223>/modified base = "2'-deoxy-2'- Fluorine-related nucleotides &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt; A base &lt;222>4, 8, 9, 10, 11, 12, 14, 16, 17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 319

Ucuauuugaa gauaugacut t 21 &lt;210> 320 &lt;211> 21 &lt;212> DNA 158- 152219 · Sequence Listing _doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Reverse of dsRNA Stocks &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt; 222>4,6,12,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide"

&lt;221〉 modified-base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3,5, 7,8,9,10,11, 13,14,15, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 320 agucauaucu ucaaauagat t 21

&lt;210> 321 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 5, 6, 7 ,13, 15, 18, 19 -159- 1522〗 9. Sequence Listing.doc 201130494 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 8, 9,10 , 11, 12, 14, 16, 17 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400&gt; 321 ucuauuugaa gauaugacut t 21 &lt;210&gt; 322 &lt;211&gt; 21 &lt;;212>DNA&lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222>4,6,10,12,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3,5, 7, 8,9,11,13,14,15, 17, &lt;223>/modified base = "25. hydroxyl corresponding nucleotide" &lt;400> 322 agucauaucu ucaaauagat t 21 &lt;210> 323 &lt;211&gt; 21 160-152219 · Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;&lt;221〉 modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base

&lt;222>1,2,3,5,6,7, 13,15,18, 19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;;220>&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'_ phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>4,8 , 9, 10, 11, 12, 14, 16, 17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 323 ucuauuugaa gauaugacut t 21 &lt;210> 324 &lt; 21 &lt;212&gt; DNA <213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 4, 6, 8,9,10, 11,12,16 &lt;223>/modified base = "2'_deoxy-2' fluoride corresponding nucleotide" &lt;220> &lt;221&gt; modified_base -161 - 152219 - Sequence Listing.doc 201130494 &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 5 , 7, 13,14, 15,17, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt 400> 324 agucauaucu ucaaauagat t 21 &lt;210> 325 &lt;2Π&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220 〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of 5s phosphate group" &lt;220> &lt;221> modifiedjbase &lt;222>1,4 , 8, 9, 11, 12,13, 15,16, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 5, 6, 7, 10 , 14, 17, 19 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 325 caacaaacua uuugucgcat t 21 &lt;210&gt; 326 •162·

152219· Sequence Listing.doc 201130494 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lacking 5; -phosphate group" &lt;220> &lt;221> modified-base

&lt;222&gt; 6, 10 &lt;223&gt;/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified") ase &lt;222> 21 &lt;223 〉/modified base = "5'-thiolate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 4,5,7,8,9,11, 12,13, 14, 15, 16,17,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 326 ugcgacaaau aguuuguugt t 21

&lt;210> 327 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lacking 5, phosphate group" &lt;220> -163- 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>2, 3,4,5, 6, 8,9, 11,13 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 7, 10,12, 14,15, 16, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 327 aucuucauca uacgaaggat t 21 &lt;210> 328 &lt;211> 21 &lt;212〉 DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = " Nucleotide: lack of 5'-phosphate group" &lt;220&gt; &l t;221&gt; modified_base &lt;222&gt; 8 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223 〉/modified base = "5'· phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,2, 3, 4, 5,6,7,9, 10 , 11, 12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -164- 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 328 uccuucguau gaugaagaut t 21 &lt;210〉 329 &lt;211> 21 &lt;212> DNA &lt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: sRNA's sensible stock &lt; 220〉

&lt;221〉 modified-base &lt;223&gt;/modified base = "nucleotide: lack of 5'-filling acid group" &lt;220> &lt;221> modified-base &lt;222>1,2, 3,4,5, 7,10,14,15, 17, 18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; Fflodified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>6, 8, 9, 11,12, 13, 16 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400> 329 cucucgcaac aaacuauuut t 21 &lt;210> 330 &lt;211&gt; 21 &lt;212> DNA &lt;213 〉Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA-165- 152219-sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 4 &lt;223>/modified base = "2'·0·methyl Corresponding nucleotides &lt;220〉 &lt;221〉 modified-base &lt;222&gt; 21 &lt ;223>/modified base = "55 · phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3,5, 6,7,8,9,10, 11,12, 13, &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400&gt; 330 aaauaguuug uugcgagagt t 21 &lt;210&gt; 331 &lt;211&gt; 21 &lt;212&gt; DNA &lt;;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 5, 6,7,8,9, 11, 12, 14, 16 &lt;223>/modified base Base == "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 -166- 152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "5'-Thiophosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 10, 13, 15, 17, 18, 19 &lt;223>/modified base = "2~hydroxy corresponding nucleotide" &lt;400&gt; 331 ugaaucuuca ucauacgaat t 21

&lt;210&gt; 332 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>5,18 &lt;223>/ Modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-thiolate Thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3,4, 6, 7,8, 9,10,11,12, 13, &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" &lt;400&gt; 332 uucguaugau gaagauucat t 21 &lt;210&gt; 333 &lt;211&gt; 21 167· 152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence&lt;;220>&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' Phosphate group" &lt;220&gt;&lt;221〉 modified_ba Se &lt;222>1, 5, 6,7,8,9, 10, 14,15, 17,18, 19 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base == "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 2,3, 4,11, 12,13, 16 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 333 cagaccuucc agaucgcuut t 21 &lt;210> 334 &lt;211 〉 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt; 223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221〉 modified_base -168·

152219·Sequence List.doc 201130494 &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 334 aagcgaucug gaaggucugt t 21

&lt;210&gt; 335 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lacking 5:-filling acid group" &lt;220&gt;&lt;221> modified-base &lt;222>1,5,6,8, 9,10, 11,12, 13,14, 13⁄4 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4, 7,17,19 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 335 cagaucgcuu ccucucgcat t 21 &lt;210&gt; 336 -169- 152219-sequence table.doc 201130494 &lt;211&gt; 21 &lt;212> DNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-phosphate group" &lt;220〉 &lt;221&g t; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1. · 19 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 336 ngcgagagga agcgaucugt t 21 &lt;210&gt; 337 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 2,8,10, 13, 14,16, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleoside Acid" &lt;220&gt; •170·

152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base == "55-phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt;222 〉3,4,5,6, 7,9, 11,12, 15, 17,18 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 337 cuagagguau ggcuguaact t 21 &lt;210&gt; 338 I &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt;&lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base • &lt;222>3,5,9, 11,17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'. Phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1,2,4, 6, 7,8,10,12,13, 14, 15, &lt;223> / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 338 guuacagcca Uaccucuagt t 21 • 171 - 152219 - Sequence Listing.doc 201130494 &lt;210> 339 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220〉 &lt;223> Description of Artificial Sequence: DsRNA Stocks &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>2,3,4, 6, 7, 10, 13, 15,17, 18,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1, 5,8, 9, 11,12, 14, 16 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 339 auuuauugac aauacgcuut t 21 &lt;210> 340 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223&gt; / Modified base = "nucleotide: lack of 5'-phosphate group -172·

152219· Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 6, 12, 15 &lt;223&gt;/modified base = "2^0-fluorenyl corresponding nucleotide" &lt;220&gt;;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3 , 4,5,7,8,9, 10,11, 13,14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" ^ &lt;400&gt; 340 aagcguauug ucaauaaaut t 21 &lt ;210> 341 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222 〉 1 stomach &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,5,7,9,10,11 , 12,14, 15,16,17, &lt;223>/modified base = "2^0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221〉 modified-base &lt;222>1,3,4, 6, 8, 13, 18 152219_ Sequence Listing.doc -173- 201130494 &lt;223>/modified base = "2'-hydroxy corresponding core "Glycosylation" &lt;400> 341 acaauacgcu uuacuuuaut t 21 &lt;210&gt; 342 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense of dsRNA Stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222 〉2, 7, 14 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified Base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 15 , &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 342 auaaaguaaa gcguauugut t 21 &lt;210&gt; 343 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: dsRNA The right stock -174- 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt;220&gt;&lt;221〉 modified-base &lt;222>2, 9, 11, 12,13,14, 15, 16,19 &lt;223>/modified base = "2'-0·A The corresponding nucleotide " &lt; 220 > &lt; 221 > modified - base &lt; 222 > 21 &lt; 223 > / modified base = = "5 ' · phosphorothioate thymidine"

&lt;220&gt;&lt;221> modified_base &lt;222>1,3,4,5,6,7, 8,10, 17, 18 &lt;223>/modified base == "2'-hydroxy corresponding core "Glycosylation" &lt;400&gt; 343 acgaaggaua cuuucuagct t 21 &lt;210> 344 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220&gt;221&gt; modified_base &lt;222&gt; 3, 10 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified one Base • 175· 152219 - Sequence Listing.doc 201130494 &lt;222&gt; 21 &lt;223&gt; / modified base = "5'_ phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1, 2,4, 5, 6, 7,8,9, 11,12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 344 gcuagaaagu Auccuucgut t 21 &lt;210&gt; 345 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; Modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>5,6, 8, 9, 10,1], 12, 13,16, 18 &lt;223〉/modified Base = "25-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;;220>&lt;221> modified-base &lt;222>1, 2, 3,4, 7,14,15,17, 19 &lt;223>/modified thiol = "2' hydroxy corresponding nucleotide &lt;400> 345 ggaauugucu cccagugcat t 21 &lt;210&gt; 346 -176- 152219·sequence table.doc 201130494 &lt;211> 21 &lt;212> DMA &lt; 213 &gt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; Description of the sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220&gt ;

&lt;221〉 modified_base <222&gt; 3,13 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,4, 5,6,7, 8,9, 10,11,12,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 346 ugcacuggga gacaauucct t 21

&lt;210&gt; 347 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222> 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> • 177- 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222 〉1, 4, 5,6, 8, 10,13,14,15, 16 &lt;223>/modified base==“2′-0·methyl corresponding nucleotide” &lt;220〉 &lt; 221> modified_base &lt;222> 21 &lt;223>/modified base == "55-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,7,9, 11,12, 17,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 347 cagucuacac agcuucgggt t 21 &lt;210&gt; 348 &lt;211> 21 &lt; 212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5s · acid ester base" &lt;220 &lt;2 21&gt; modified_base &lt;222> 13 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/ Modified base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221> modified-base &lt;221>1,2, 3, 4, 5,6,7, 8,9,10 , 11, 12, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" • 178- 152219-sequence table.doc 201130494 &lt;400&gt; 348 cccgaagcug uguagacugt t 21 &lt;210&gt; 349 &lt ; 21 &lt; 21 &gt; 212 > DNA &lt; 213 > Artificial Sequence &lt; 220 &gt;&lt; 223 &gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt; 220 &lt; 221 &gt; 221 &gt; modified_base φ &lt; 222 &gt; 1 &lt; 223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221> modified-base &lt;222>2, 3, 5, 7, 14, 16, 17 , 18, 19 &lt; 223 > / modified base = "2'·0· thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220&gt;

&lt;221&gt; modified_base <222> 1, 4, 6, 8, 9, 10, 11, 12, 13, 15 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt 349 aucauacgaa ggauacuuut t 21 &lt;210> 350 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA-179- 152219- Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt; 221> modified-base &lt;222&gt; 5, 14 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt ;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1, 2, 3,4,6, 7, 8,9 , 10,11, 12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 350 aaaguauccn]丨lcgua.ugaut t 2] &lt;210> 351 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of the column: Sensed Strands of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 6,7, 8,9,10,12, 13, 15,17 &lt;223>/modified base == "2'-0· thiol corresponding Nucleotide &lt;220&gt;&lt;221> modified_base &lt;222> 21 •180· 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3, 4, 5, 11, 14, 16, 18, 19 &lt;223>/modified base == "2s-hydroxy corresponding nucleotide" &lt;400&gt; 351 uugaaucuuc aucauacgat t 21

&lt;210> 352 &lt;211> 21 &lt;212> DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; Description of artificial sequence: antisense strand of dsRNA &lt; 220 &lt; 221 &lt; 221 &gt; modified jmse &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>4,17 &lt;223>/modified base Base = "Γ-0-曱-based corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;;220&gt;&lt;221〉 modified-base &lt;222>1,2,3,5, 6,7, 8, 9, 10, 11,12, 13, &lt;223>/modified base = "2 '·Hydroxyl corresponding nucleotides &lt;400&gt; 352 ucgua.uga.ug aagauucaat t 21 &lt;210&gt; 353 &lt;211&gt; 21 181 · 152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5 '-phosphate group &lt;220> &lt;221> modified-base &lt; 222>1, 2, 3,7, 8,9, 10,11,13,14,16, &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220 〉 &lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4, 5,6, 12,15, 17,19 &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400> 353 uuugaaucuu caucauacgt t 21 &lt;210&gt; 354 &lt;211> 21 &lt;;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; Base = "nucleotide: lack of 5'-phosphate group &lt; 220> &lt;221> modified-base • 182· 152219-sequence table.doc 201130494 &lt;222&gt; 3, 16 &lt;223>/modified base Base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate chest Glycoside &lt;220> &lt;221> modified-base &lt;222>1, 2, 4, 5,6,7, 8, 9, 10,1 1, 12, 13, 14, &lt;223>/modified base = "2'_hydroxy corresponding nucleotide" &lt;400&gt; 354

Cguaugauga agauucaaat t 21 &lt;210> 355 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA rational stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3,4, 6,7 , 8, 9, 10,11,12,13,14, 16, &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified- Base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 5,15,17, 18 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" -183- 152219 · Sequence Listing.doc 201130494 &lt;400&gt; 355 gaucgcuucc ucucgcaact t 21 &lt;210&gt; 356 &lt;211&gt; 21 &lt;;212>DNA&lt;213>ArtificialSequence&lt;220>&lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220〉

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxyl Corresponding nucleotides &lt;400&gt; 356 guugcgagag gaagcgauct t 21

&lt;210&gt; 357 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt; -184· 152219· Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>5 , 7,10, 11,13,16,17,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222〉 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1, 2, 3, 4, 6, 8, 9, 12,14, 15,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400&gt; 357 gagguauggc uguaacuaut t 21 &lt;210&gt; 358 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1 | &lt;223&gt;/modified base = "nucleotide: lack of 5'-filling acid group" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>2, 6, 8,12,14 &lt;223>/modified base = "25-0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3,4, 5, 7, 9,10,11, 13,15 ,16,17, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" 185- 152219 · Sequence Listing.doc 201130494 &lt;400> 358 auaguuacag ccauaccuct t 21 &lt;210&gt; 359 &lt; 211 &gt; 21 &lt;212&gt; DNA <213> artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: Less 5'·phosphate group” &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3, 4,9, 11, 14, 17 &lt;223>/modified base == "25- 0·methyl corresponding nucleotide” &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt; 221> modified_base &lt;222>5,6,7,8,10, 12,13,15, 16, 18,19 &lt;223>/modified base = "2~hydroxy corresponding nucleotide" &lt;400&gt ; 359 ucccaggaca ugauaauaat t 21 &lt;210> 360 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA •186·

152219·Sequence list.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,5,8 &lt;223&gt;/modified base = "2'-0.methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine"

&lt;221&gt; modified_base &lt;222>1,3,4,6,7, 9,10, 11, 12,13,14, 15, &lt;223>/modified base = "2'·hydroxy corresponding core "Glycosylation" &lt;400&gt; 360 uuauuaucau guccugggat t 21 &lt;210> 361 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence

&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of rosin phosphate group" &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2,3, 5,7,10, 11,12, 13 &lt;223>/modified base = "2'·0·methyl corresponding core "Glycolic acid" &lt;220> &lt;221> modified-base &lt;222> 21 -187- 152219-sequence table.doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4,6, 8,9, 14,15, 16, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid &lt;400> 361 ucuacacagc uucgggaagt t 21 &lt;210&gt; 362 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 16 &lt;223>/modified base = "25-0-fluorenyl phase Nucleotide &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-thiolate thymidine" &lt;220> &lt;221&gt; modified_base &lt;;222>1,2, 3, 4, 5, 6,7, 8, 9,10,11,12, &lt;223>/modified base = "2s-hydroxy corresponding nucleotide" &lt;400〉 362 cuucccgaag cuguguagat t 21 &lt;210> 363 &lt;211&gt; 21 188- 152219 - Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: dsRNA Sensed stock &lt;220&gt;&lt;221&gt; modified_ba-se &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; Modified_base

&lt;222>1,2,3,4,6,9, 13, 14,16, 17,18 &lt;223>/modified base = "2'-0 methyl corresponding nucleotide" &lt;220 〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>5,7 , 8, 10, 11, 12, 15, 19 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 363 ucucgcaaca aacuauuugt t 21 &lt;210&gt; 364 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt; 220 &lt; 221 &gt; 221 > modified - base &lt; 222 > 1 &lt; 223 > / Modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base • 189- 152219 - Sequence Listing.doc 201130494 &lt;222〉 1, 5 &lt;223〉/ Modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "55·deuterated phosphate chest Glycoside &lt;220> &lt;221> modified-base &lt;222>2,3, 4, 6, 7,8, 9, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 364 caaauaguuu guugcgagat t 21 &lt;210&gt; 365 &lt;211&gt; 21 &lt ;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; Base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221&gt; modified_base &lt;222>4,5,7, 8, 9,11, 13,14, 15,16 &lt; 223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-sulfur Phosphate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,2,3,6,10,12,17, 18,19 &lt;223>/modified base = "2'- Hydroxy corresponding nucleotide" -190- 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 365 gaaucacuug cacuccggat t 21 &lt;210> 366 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;2 20〉

&lt;221〉 modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222> 10 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5 '·Thionothioate thymidine” &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, &lt;223> / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 366 uccggagugc aagugauuct t 21 &lt;210> 367 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> • 191 - 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nuclear Glycoside: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,5,6, 7, 11, 12,14, 15' 18, 19 &lt;223>/modified Base = "2'-0-thiol corresponding nucleotide" &lt;220〉 &lt;221 &gt; rao Dified_ba.se &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,4, 8, 9,10, 13,16,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 367 ugaaucuaaa uuaucaguct t 21 &lt;210&gt; 368 &lt;211&gt; 21 &lt; 212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>7,12,18 &lt;223>/modified base = "2'-0-methyl Corresponding nucleotides j &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" -192- 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221> modified_base &lt;222>1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 13, 14, &lt;223>/modified base = "2' ·Hydroxyl corresponding nucleotide" &lt;400&gt; 368 gacugauaau uuagauucat t 21 &lt;210&Gt; 369 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence

&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-discolate Base &lt;220〉 &lt;221&gt; modified_base &lt;222>4, 5, 6, 7,8,9,10,13, 16, 18,19 &lt;223>/modified base = "2'- 0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base <222> 1, 2, 3, 11, 12, 14, 15, 17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 369

Gaauccuccu gauaacauct t 21 &lt;210> 370 &lt;211> 21 &lt;212> DNA 193 · 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: The Reverse of dsRNA Stocks &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt; 222>6,9 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base Base == "5'-Thionothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3, 4, 5, 7, 8,10, 11,ϋ2, 13,14 , &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 370 gauguuauca ggaggauuct t 21 &lt;210> 371 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5 '·Acidate base> &lt;220〉 &lt;221〉 modified_base &lt;222>6, 8, 11, 12, 14,17,18 -194· 152219-sequence table.doc 201130494 &lt;223>human modified base = "2'·0-fluorenyl Corresponding nucleotides &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; Modified_base &lt;222>1, 2, 3,4, 5, 7,9, 10, 13, 15,16,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 371 agagguaugg cuguaacuat t 21

&lt;210> 372 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;220&gt;&lt;221> modified_base &lt;222>1,5, 7, 11,13 &lt;223>/modified base = "2'-0-mercapto corresponding nucleotide" &lt;220〉 &lt;;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5^deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified a base &lt;222> 2, 3, 4, S, 8,9, 10, 12, 14, 15, 16, 17, &lt;223>/modified base = "Γ·hydroxy corresponding nucleotide" &lt;400> 372 -195- 152219· Sequence Listing.doc 201130494 uaguuacagc cauaccucut t 21 &lt;210> 373 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Sensed Strands of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; / modified base = "nucleotide: lacking 5; - phthalate group" &lt;220&gt;&lt;221> modified-base &lt;222 〉2, 3,4,5, 10,12, 15,18 &lt;223>/modified base=methyl corresponding nucleotide” &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223 〉/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modifie D_base &lt;222>1, 6, 7,8, 9,11, 13, 14, 16,17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400〉 373 gucccaggac a.ugauaauat t 21 &lt;210&gt; 374 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221〉modified a ha.se -196-

152219 - Sequence Listing.doc 201130494 &lt;222&gt; 1 &lt;223>/modified base == "nucleotide: lack of 5' phthalate group" &lt;220&gt;&lt;221> modified-base &lt; 222>1,4,7 &lt;223&gt;/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223&gt; / Modified base = "55-phosphorothioate thymidine" &lt;220〉

&lt;221〉 modified-base &lt;222>2, 3,5,6,8,9, 10,11,12,13, 14,15, &lt;223>/modified base = "2'·hydroxyl Corresponding nucleotides &lt;400> 374 uauuaucaug uccugggact t 21 &lt;210> 375 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Sensed stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; / modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modified— Base &lt;222>3, 6,8,9,15,17 &lt;223>/modified base = "25-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222 〉 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" • 197- 152219 - Sequence Listing_如〇201130494 &lt;220&gt;&lt;221&gt; niodified_base &lt;222>1, 2 , 4,5,7,10, 11, 12, 13, 14, 16, 18, &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 375 gauaacauca aggauacaat t 21 &lt;210&gt; 376 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;213&gt;;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' Phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>4,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt ; modified_base &lt;222> 21 &lt;223>/modified base = "5'·thiophthalate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 376 uuguauccuu gauguuauct t 21 &lt;210&gt ; 377 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence 198-152219-sequence table.doc 201130494 &lt;220&gt;&lt;223&gt;223 Description of artificial sequence: sRNA sine stock &lt;220&gt;&lt;;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>2, 6 , 7,9, 10,11,13, 14, 16 &lt;223〉/ Base = "2'-O-methyl nucleotides corresponding to" &lt; 220>

&lt;221&gt; modified_baLse &lt;222> 21 &lt;223&gt;/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,3, 4,5,8, 12,15,17, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 377 acaaacuauu ugucgcaggt t 21

&lt;210> 378 &lt;211> 21 0 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate base" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 8, 12 &lt;223>/ Modified base = "2'-0-fluorenyl corresponding nucleotide" -199- 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-Thiophosphate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2, 3,4,5, 6, 7, 9, 10,11, 13, 14, &lt;;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 378 ccugcgacaa auaguuugut t 21 &lt;210> 379 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;213&gt;;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base == "nucleotide: lack of 55- Phosphate group" &lt;220&gt;&lt;221&gt; modified_bas e &lt;222>6,8, 9,10, 11, 12, 13,16,17,18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt ; &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3 , 4, 5, 7, 14, 15,19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 379 aaggauacuu ucuagcuugt t 21 •200 1522丨9-sequence table.doc 201130494 &lt;210&gt; 380 &lt;211> 21 &lt;212> DMA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &lt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt;220 &lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;220> &lt;221&gt; modified_base &lt;222>1,6,13 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" <220> &lt;221> modified one Base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 3, 4, 5, 7,8,9, 10,11,12, 14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" ^ &lt;400&gt; 380 caagcuagaa aguauccuut t 21 &lt;210&gt; 381 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 - 201 - 152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'·filling acid group" &lt;220&gt;&lt;221> modified-base &lt;222>1, 3, 4,9, 10, 11, 12,14, 16, 17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt; &Lt;221&gt; modified_base &lt;222>2, 5, 6,7,8, 13, 15,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 381 uauuaaaauu ucaugccggt t 21 &lt;210> 382 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified-base &lt;222&gt; 15, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220> • 202- 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>1,2,3,4,6,7, 8, 9,10, 11, 12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 382 ccggcaugaa auuuuaauat t 21 &lt;210&gt; 383 &lt;211&gt; 21 &lt ;212&gt; DNA &lt;213>Artificial Sequence&lt;220〉

&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; inodified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 55-phosphate group" &lt;220〉 &lt;221&gt; modified_base &lt;222>], 4, 5, 8, 9, 10, 16, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 2,3, 6,7, 11,12,13,14, 15, 17,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 383 uagccagccu agagguaugt t 21 &lt;210> 384 &lt;211> 21 &lt;212> DNA &lt; 213> artificial sequence 203 · 152219 · Sequence Listing. doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3,9,18 &lt;223>/modified base = " 2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5^ phosphorothioate thymidine" &lt; 220> &lt;221〉 modified-base &lt;222>2,4, 5, 6, 7, 8, 10,11,12,13, 14, &lt;223>/modified base = "2'·hydroxyl Corresponding nucleotides &lt;400&gt; 384 cauaccucua ggcuggcuat t 21 &lt;210&gt; 385 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt;220 &lt; 223 &gt; 223 &gt; Description of artificial sequence: dsRNA Sensed stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-decarboxylate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1, 4, 5, 7, 8, 12, 13, 16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" -204- 152219 - Sequence Listing. Doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222> 2,3,6, 9, 10, 11, 14,15,17, 18, 19 &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&gt;&lt;400> 385 uggcugcuga accaguagat t 21 ^ &lt;210&gt; 386 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Artificial sequence Description: Antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;

&lt;221〉 modified-base &lt;222>3, 11, 14, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 4, 5, 6, 7 , 8, 9, 10, 12, 13, 15, &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotides" &lt;400&gt; 386 ucuacugguu cagcagccat t 21 • 205 - 152219 - Sequence Listing. Doc 201130494 &lt;210&gt; 387 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; moclified_base &lt;222>5, 6,8,9, 10 , 12, 14, 15, 16,17 &lt;223>/modified base = "2M> thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/ Modified base = "5; - phosphorothioate thymidine" &lt;220> &lt;221> modi Fied_base &lt;222>1,2,3, 4, 7,11,13, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 387 agaaucacuu gcacuccggt t 21 &lt;210> 388 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" -206-

1522丨9-Sequence List.doc 201130494 &lt;220&gt;&lt;221> modified_base &lt;222&gt; 9 &lt;223>/modified base = "2'-0-mercapto corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 4,5, 6,7, 8,10, 11,12, 13,14, 15,16,17,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400> 388 ccggagugca agugauucut t 21 &lt;210&gt; 389 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified base &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>2,3,8, 9,10, 11, 13,15,16 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt; 223>/modified base = "5~ phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base • 207· 152219·sequence table.doc 201130494 &lt;222>1,4,5, 6, 7 , 12, 14, 17, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 389 auuaaaauuu caugccgggt t 21 &lt;210> 390 &lt;211> 21 &lt ;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; Base = "nucleotide: missing 5'- Acidate group &lt;220> &lt;221&gt; modified_base &lt;222>6,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt ; modified_ba.se &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221>modified_ba_se &lt;222>1,2,3, 4 , 5, 7, 8, 9,10, 11, 12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 390 cccggcauga aauuuuaaut t. 21 &lt;210 〉 391 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt; 208-1522丨9·SEQ ID list.doc 201130494 &lt;223> Description of artificial sequence··sense stock of dsRNA&lt; 220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_bs-se &lt;222&gt; 1,3,6,7, 8, 10,12,15, 16,17,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;

&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 4, 5, 9, 11, 13, 14, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 391 ugcagucuac acagcuucgt t 21 &lt;210> 392 &lt;211> 21 &lt;212>DNA&lt;213>Artificialsequence&lt;220>&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; = "nucleotide: lacking 55·phosphate group" &lt;220&gt;&lt;221&gt; tnodified_base &lt;222> 11, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleoside Acid &lt;220> -209- 152219·SEQ ID NO.doc 201130494 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>1, 2,3,4,5,6, 7,8,9, 10,12,13, &lt;223>/modified base = "25-hydroxy corresponding core "Glycosylate" &lt;400&gt; 392 cgaagcugug uagacugcat t 21 &lt;210&gt; 393 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modifiedjbase &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3,4, 5,7, 10,12, 13 , 14, 16, 17, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/ Modified base = "5'-thiophosphate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,2, 6, 8, 9,11, 15, 18 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 393 gaucuauaau guucacugut t 21 -210- 152219 · Sequence Listing.doc 201130494 &lt;210&gt; 394 &lt;211> 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence·· Antisense stock of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-filled acid ester group &lt;220&gt;

&lt;221〉 modified_base &lt;222>2,9,12, 14 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-halogenated phosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4, 5, 6, 7 , 8, 10, 11, 13, 15, 16, &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400&gt; 394 acagugaaca uuauagauct t 21 &lt;210> 395 &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; Modified base = "nucleotide: lack of 5' phosphate group" -211 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 5, 6, 7,9, 11,14, 15,16, 17 &lt;223>/modified base == "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt ;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221 Modified—base &lt;222>1,3,4, 8, 10,12, 13,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 395 gcagucuaca Cagcuucggt t 21 &lt;210&gt; 396 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; Modified_base &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 12 &lt;223>/ Modified base = "25·0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine &lt;220〉 &lt;221> modified_base &lt;221>1, 2,3,4,5, 6, 7, 8, 9, 10, 11, 13, -212- 152219 · Sequence Listing.doc 201130494 &lt; 223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 396 ccgaagcugu guagacugct t 21 &lt;210&gt; 397 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223> Description of artificial sequence: the meaning of dsRNA

&lt;220> &lt;221> modified base &lt;222> 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-filling acid group" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>1, 2,7,8, 9,10,12, 14, 15, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt; 221> modified_base &lt;222> 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>3, 4, 5 , 6,11,13,16,17,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 397 uuaaaauuuc augccgggct t 21 &lt;210> 398 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA-213· 152219-sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 55-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 7, 17 &lt;223>/ Modified base = "2'·0-methyl corresponding nucleotide j &lt;220&gt;&lt;221> modifi Ed-base &lt;222&gt; 21 &lt;223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5,6,8, 9, 10, 11,12,13,14, 15,16,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 398 Gcccggcaug aaauuuuaat t 21 &lt;210&gt; 399 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 &gt; 223 > description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221 〉 modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221> modified-base &lt;222>3, 7,8,10, 11, 12,14, 15,17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified base • 214 · 152219 · Sequence Listing.doc 201130494 &lt;222> 21 &lt;223>/modified base == "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 2, 4, 5,6,9, 13,16,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400&gt; 399 aacaaacuau uugucgcagt t 21

&lt;210&gt; 400 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 7, 11 <223> / modified base Base = "2'-0. thiol corresponding nucleotide"

&lt;221〉 modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1, 2, 3, 4, δ, 6, 8, 9, 10, 12, 13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 400 cugcgacaaa uaguuuguut t 21 &lt ;210> 401 -215- 152219-Sequence table.doc 201130494 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence·· s. 220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lacking 55·phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3, 4,5, 7,8,11,14, 16, 18,19 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,6, 9,10,12, 13,15,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 401 Aauuuauuga caauacgcut t 21 &lt;210&gt; 402 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> -216· 1522〗 9-sequence table.doc 201130494 &lt;221&gt; Modified_base &lt;222>5,11, 14 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;;223>/modified base = "5'. phosphorothioate thymidine" &lt;220&gt; · &lt;221> modified-base &lt;222>1,2,3,4,6, 7, 8, 9,10,12,13,15, &lt;223>/modified base = "2s-hydroxy corresponding nucleotide"

&lt;400&gt; 402 agcguauugu caauaaauut t 21 &lt;210> 403 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>5, 6,7,8, 10,12, 13, 17,19 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222 〉 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1,2, 3,4,9, 11, 14,15, 16,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" • 217- 152219 · Sequence Listing.doc 201130494 &lt;400&gt; 403 aaaauuucau gccgggcgct t 21 &lt;210&gt; 404 &lt;211> 21 &lt;212> DNA &lt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;;223>/modified base = "nucleotide : lack of 55-phosphate group" &lt;220> &lt;221> modified_base &lt;222> 9 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1, 2, 3, 4 , 5, 6, 7, 8, 10, 11, 12, 13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 404 gcgcccggca ugaaauuuut t 21 &lt;210〉 405 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA-218- 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;;221〉 modified-base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5; -phosphate group" &lt;220> &lt;221> modified-base &lt;222>2 , 4, 7, 10,12, 14, 16, 17,18,19 &lt;223>/modified base = "25-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5' · phosphorothioate thymidine"

&lt;221〉 modified_base &lt;222>1,3, 5,6,8,9,11, 13,15 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 405 Guguagugac gcaugcccut t 21 &lt;210> 406 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: absent 55_Acate group" &lt;220> &lt;221> modified-base &lt;222>5,12,15,17 &lt;223>/modified base = "2'·0·methyl corresponding nucleoside Acid &lt;220> &lt;221> modified-base &lt;222&gt; 21 -219- 152219-sequence table.doc 201130494 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220〉 &lt;221〉 modified_base &lt;222>1, 2, 3, 4, 6,7, 8,9, 10, 11, 13,14, &lt;223>/modified base = "25- Hydroxy corresponding nucleotide" &lt;400&gt; 406 agggcaugcg ucacuacact t 21 &lt;210> 407 &lt;211> 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220&gt;&lt;223&gt; Right stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>4,5,6, 8,9,12,15, 17,19 &lt;223>/ Base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-thiophosphoric acid Ester thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 7, 10, 11, 13, 14, 16, 18 &lt;223>/modified base = "2'· Hydroxyl corresponding nucleotides &lt;400> 407 aaauuuauug acaauacgct t 21 &lt;210&gt; 408 &lt;211&gt; 21 152219 · Sequence Listing. doc -220 - 201130494 &lt;212> DNA &lt; 213 > Artificial Sequence &lt; 220〉 &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-caprate Base &lt;220&gt;&lt;221&gt; modified one base &lt;222>4, 10, 13

&lt;223&gt;/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5' - Deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3, 5,6, 7, 8, 9,11, 12, 14,15, &lt;223>/ Modified base = "2'_hydroxy corresponding nucleotide" &lt;400> 408 gcguauuguc aauaaauuut t 21 &lt;210&gt; 409 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dishate group &lt;220&gt;&lt;221> modified_base • 221 · 152219 - Sequence Listing.doc 201130494 &lt;222>2,3,6, 7,15, 16,19 &lt;223>/modified base = "2' "0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "55 · phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,4,5, 8,9,10,11, 12, 13,14,17 18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 409 auugaccaag gaaaucggct t 21 &lt;210&gt; 410 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified__base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: missing 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222> 16 &lt;223>/modified base == "25-0·methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'-thio-sulfonate thymidine" &lt;220> &lt;221>modifiedjbase &lt;222>1,2,3 ,4,5,6, 7, 8,9,10, 11, 12, 13,14,15, 17,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -222· 152219-Sequence table.doc 201130494 &lt;400&gt; 410 gccgauuucc uuggucaaut t 21 &lt;210> 411 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description: Sensed Shares of dsRNA &lt;220〉 &lt;221&gt; mo Dified_base •&lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1,3,6,9, 11,13,15,16,17, 18,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base

&lt;222>2,4, 5, 7,8,10, 12,14 &lt;223&gt; / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 411 uguagugacg caugcccuct t 21 &lt; 210> 412 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; . &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; - 223 - 152219 - Sequence Listing. Doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>6, 13,16, 18 &lt;223>/modified base == "2'-0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified Base = "5'. Phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3, 4,5, 7,8, 9,10, 11, 12,14 , &lt;223>/modified base == "2'·hydroxy corresponding nucleotide j &lt;400&gt; 412 gagggcaugc gucacuacat t 21 &lt;210&gt; 413 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Stocks &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221> modified_base &lt; 222>1,2, 6, 7,9, 11, 12,13, 15, 16, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-thiophthalate thymidine" -224 - 1522丨9_sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>3,4, 5,8, 10, 14, 17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 413 ccggaccaua uuuauuauat t 21 &lt;210> 414 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence • &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222&gt; 1, 3, 6, 10 &lt; 223>/modified base = "2'-0_ thiol corresponding nucleotide" &lt;220〉

&lt;221〉 modified_base &lt;222> 21 &lt;223&gt;/modified base = "5~ phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2, 4,5 , 7, 8, 9, 11, 12, 13, 14, 15, 16, &lt; 223 > / modified base = "25 · hydroxyl corresponding nucleotide" &lt; 400 > 414 uauaauaaau augguccggt t 21

&lt;210> 415 &lt;211&gt; 21 &lt;212> DNA -225 - 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA ;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3 ,Ί,7,8,9,15,17 &lt;223>/modified base == "2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 5, 6, 10, 11, 12, 13, 14, 16, 18, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 415 agccagccua gagguauggt t 21 &lt;210> 416 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nuclear Glycosidic acid: lack of 5'-phosphate group" &lt;220〉 &l t;221> modified_base &lt;222>2,4, 10 -226· 152219·sequence table.doc 201130494 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220 〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 3 , 5, 6, 7, 8,9,11, 12, 13,14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 416 ccauaccucu aggcuggcut t 21

&lt;210> 417 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&lt;221&gt;&lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group"

&lt;220〉 &lt;221〉 modified_base &lt;222>2,5, 8, 10, 12,14,15,16,17,18 &lt;223>/modified base = "25·0·methyl corresponding Nucleotide &lt;220&gt;221&gt; modified_ba.se &lt;222> 21 &lt;223&gt;/modified base = "5'-deuterated phosphate thymidine" &lt;220&gt;&lt;221&gt; A base &lt;222>1,3,4, 6, 7, 9, 11,13, 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 417 • 227 · 152219 - Sequence Listing.doc 201130494 guagugacgc augcccucat t 21 &lt;210> 418 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense of dsRNA Stock &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lacking 5'·stearate group" &lt;220&gt;&lt;221> modified_base &lt; 222>7,14,17 &lt;223>/modified base = "25-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified Base = "5'-thiophosphate thymidine" &lt;220> &lt;221&gt; modifie D_base &lt;222>1,2,3,4,5, 6,8, 9,10, 11, 12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;;400&gt; 418 ugagggcaug cgucacuact t 21 &lt;210&gt; 419 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;;&lt;221> modified base • 228 · 152219 - Sequence Listing.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220&gt;&lt;221〉 modified_base &lt;222>3,5,7,9, 10, 11,12,13⁄4 16, 17, 18, &lt;223>/modified base = "fO-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "55-deuterated phosphate thymidine" &lt;220> &lt;221>modified-base &lt;222&gt; , 2, 4, 6, 8, 14 &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 419 gacgcaugcc cucaauccct t 21 &lt;210> 420 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-can acid ester "220" &lt;221> modified-base &lt;222> 12 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221〉 modified A base &lt;222&gt; 21 &lt;223&gt; / modified base = "5 \ phosphorothioate thymidine" - 229 - 152219 · Sequence Listing. doc 201130494 &lt; 220 > &lt;221 &gt; modified_base &lt; 222 &gt; 1, 2,3,4, 5, 6, 7, 8, 9, 10, 11, 13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 420 gggauugagg Gcaugcguct t 21 &lt;210&gt; 421 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt; Modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222&gt; 3, 4, δ, 6, 7, 9, 10, 12, 14 &lt;223>/modified base = "2'_0_methyl phase Nucleotide &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / modified base = "5' · thiodislate thymidine" &lt;220&gt;&lt;221> modified_base &lt;;222>1,2,8,11, 13, 15,16, 17, 18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 421 aaucuucauc auacgaaggt t 21 &lt;210> 422 &lt;211> 21 &lt;212> DNA &lt; 213 > artificial sequence 230 · 152219 · Sequence Listing. doc 201130494 &lt; 220 > &lt; 223 > Description of artificial sequence: antisense stock of dsRNA ;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 7 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220&gt;

&lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2,3,4, 5, 6,8,9,10,11,12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 422 ccuucguaug augaagauut t 21 &lt;210> 423 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 55-phosphate base" &lt;220> &lt;221&gt; modifiedbase &lt;222>6,7, 10,11,12, 13, 14,16,17,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" -231 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3,4, 5, 8,9,15, 19 &lt;223>/modified base = "2'_hydroxy corresponding nucleotide" &lt;400〉 423 ggaaaucggc cucuauuugt t 21 &lt;210&gt; 424 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base <222> 1,5 &lt;223 〉/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-thio Phosphate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,3, 4, 6, 7,8,9, 10, 11, 12, 13,14, &lt;223>/ Modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 424 caaauagagg ccgauuucct t 21 -232· 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 425 &lt;211&gt; 21 &lt;212> DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide : Lack of 5'-filled acid ester group &lt;;220>&lt;221&gt; mod ifi ed_base &lt;222>1, 2,6,7, 8, 9,10,11, 15, 16,18, &lt;223>/modified base = "2' ·0·曱-based corresponding nucleotide” &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" <220> &lt;221〉 modified-base &lt;222>3, 4, 5,12,13,14,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

Ucagaccuuc cagaucgcut t 21 &lt;210&gt; 426 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222> 1 • 233 · 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 55-phosphate group" &lt;220> &lt;221&gt; modified_base &lt; 222 &gt; 21 &lt; 223 > / modified base = "5' · phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>L. 19 &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" &lt;400> 426 agcgaucugg aaggucugat t 21 &lt;210> 427 &lt;211> 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220> &lt;223&gt; Description: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lacking 5, filling ester group" &lt;220> &lt;;221&gt; modified_base &lt;222>2, 4, 7, 8,11, 12,13, 14, 17, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;221&g t; modified_base &lt;222> 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,3,5, 6, 9 , 10, 15, 16, 19 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt;400&gt; 427 -234- 152219 - Sequence Listing.doc 201130494 auaugacuga uucugacugt t 21 &lt;210 〉 428 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1

&lt;223&gt;/modified base = "nucleotide: lack of 5'-acidate group" &lt;220> &lt;221> modified-base &lt;222>1,5,11,15,17 &lt; 223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5' sulfur Phosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;221&gt;2,3,4, 6,7,8, 9,10, 12,13,14,16,18,19 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 428 cagucagaau cagucauaut t 21 &lt;210> 429 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base • 235 - 152219 - Sequence Listing.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nuclear Glycoside: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,4, 6,7, 8, 9, 15 &lt;223>/modified base = " 25-0 methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223 〉/modified base = "5:-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>3, 5, 10, 11, 12, 13, 14, 16, 17 , 18, 19 &lt;223>/modified base = "2s-hydroxy corresponding nucleotide" &lt;400&gt; 429 uugcacuccg gagguagagt t 21 &lt;210&gt; 430 &lt;211> 21 &lt;212> DNA &lt;213 〉Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222> 4, 17 &lt;223>/modified base = "2^0-methyl corresponding nucleotide" &lt; 220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5\ phosphorothioate thymidine" -236-

152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 5,6, 7,8,9,10, 11,12,13,14, 15,16, 18,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 430 cucuaccucc ggagugcaat t 21 &lt;210> 431 &lt;211&gt; 21 &lt;212> DNA &lt;213 〉Artificial sequence

&lt;220〉 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,5,7,8,9, 10,16 &lt;223>/modified base = "2'-0 "Methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222 〉4, 6,11,12,13,14,15,17,18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 431 cuugcacucc ggagguagat t 21 &lt ;210> 432 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence•237 - 152219-Sequence table_北〇201130494&lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA ;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222 〉3,16 &lt;223〉/modified base=“2 -0-thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;;221〉 modified-base &lt;222>1, 2, 4,5,6,7,8,10,11,12, 13, &lt;223>/modified base = "2'·hydroxy corresponding "Nucleotide" &lt;400> 432 ucuaccuccg gagugcaagt t 21 &lt;210> 433 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Stocks &lt;220〉 &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,4,6,8,10, 11,12,13,14,17, 18, &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" - 238- 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_b〇-se &lt;222&gt; 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt; 220> &lt;221〉 modified-base &lt;222>2, 3, 5, 7,9,15, 16 &lt;223>/modified base Base = "2'-hydroxy corresponding nucleotide" &lt;400> 433 ugacgcaugc ccucaaucct t 21

&lt;210&gt; 434 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base • &lt;222> 11, 18 &lt;223 〉/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'- Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;221>1,2, 3,4, 5, 6,7,8,9, 10,12,13, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 434 ggauugaggg caugcgucat t 21 -239- 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 435 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide : Lack of 5'-phosphate group" &lt;220〉 &lt;221 Modified_base &lt;222>1,2, 4, 6,13, 15, 16, 17, 18, 19 &lt;223>/modified base = "25·0-methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 3, 5, 7, 8, 9, 10, 11, 12, 14 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 435 ucauacgaag gauacuuuct t 21 &lt;210&gt; 436 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&lt;221&gt; modified_base &lt;222&gt;

152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>6,15, 17 &lt; 223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·琉Phospho-ester thymidine" &lt;220〉 &lt;221&gt; modified_base

&lt;222&gt; 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 436 gaaaguaucc uucguaugat t 21 &lt;210> 437 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1, 2,4,6,13,15,16,17, 18,19 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt; -241 · 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified^base &lt;222〉 3, 5, 7, 8, 9,10, 11, 12, 14 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 437 ucauacgaag gauacuuuct t 21 &lt;210〉 438 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 > artificial sequence Description: Antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt; 221> modified-base &lt;222>6,15,17 &lt;223>/modified base = "2'·deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1,2, 3, 4,5, 7, 8, 9, 10,11, 12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 438 gaaaguaucc uucguaugat t 21 &lt;210&gt; 439 &lt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence-242, 152219. Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA sine stock &lt;220&gt;&lt;221&gt; Modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2,4,6 , 13, 15,16, 17,18, 19 &lt;223>/modified base = "2'-0- Corresponding nucleotides &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / modified base = "55 · phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; Base &lt;222>3,5, 7,8, 9,10,11,12, 14 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 439 ucauacgaag gauacuuuct t 21 &lt;210&gt; 440 • &lt;211> 21 &lt;212> DNA &lt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-stearate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt;6,8,9,10, 11,12,13,15,17 &lt;223>/modified base = "2'-deoxy-2' fluoride corresponding nucleotide" • 243 - 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5~ phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5, 7,14,16, 18, 19 &lt;223>/modified base = "2:-hydroxy Corresponding nucleotides &lt;400&gt; 440 gaaaguaucc uucguaugat t 21 &lt;210&gt; 441 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; Description of artificial sequence: dsRNA Sensed stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;;222>1, 3,4,7,8, 16, 17 &lt;223>/modified base = "2M> thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5; - phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 5, 6, 9, 10, 11, 12, 13,14, 15, 18, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 441 cauugaccaa ggaaaucggt t 21 -244- 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 442 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 > artificial sequence &lt; 220 &gt;&lt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt; 220 &lt; 221 &gt; modified_base &lt; 222 > 1 &lt ;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221&gt; modified_base &lt;222>1, 15,18 &lt;223&gt;/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7, 8, 9 , 10, 11, 12, 13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 442 ccgauuuccu uggucaaugt t 21 &lt;210> 443 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; = "nucleotide: lack of 5'-phosphate group" -245 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4, 7, 8,16, 17 &lt;223&gt;/modified base = "2MD·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5; - thio Phosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2 , 5,6,9, 10,11,12, 13,14, 15,18, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 443 cauugaccaa ggaaaucggt t 21 &lt 210> 444 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222 〉 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1, 15, 18 &lt;223>/ Modified base = "2:-deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5^ Phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base-246-152219-sequence table.doc 201130494 &lt;222>2,3, 4, 5, 6, 7, 8,9, 10, 11,12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 444 ccgauuuccu uggucaaugt t 21 &lt;210> 445 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA stocks

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1, 3, 4, 7, 8, 16, 17 <223> / Modified base = "2'·0·methyl corresponding nucleotide" &lt;220> <221> modified-base &lt;222> 21 &lt;223> / Modified base = "5' · phosphorothioate thymidine"

&lt;220〉 &lt;221〉 modified-base &lt;222>2,5, 6, 9,10,11, 12, 13, 14, 15,18, &lt;223>/modified base = "2' -Hydroxy corresponding nucleotide" &lt;400&gt; 445 cauugaccaa ggaaaucggt t 21 &lt;210&gt; 446 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 247-152219 · Sequence Listing.doc 201130494 &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222>1,15,18 &lt;223>/modified base = "2'-0· Methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; Modified_base &lt;222>2, 3, 4,5,6,7, 8, 9,0,11, 12,13, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;;400&gt; 446 ccgauuuccu uggucaaugt t 21 &lt;210&gt; 447 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;;&lt;221&gt; modified_base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>1,3, 4, 7,8,16, 17 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt; -248- 152219-sequence table.doc 201130494 &lt;221> modified_base &lt;222>2, 5, 6, 9, 10,11, 12,13, 14, 15, 18, &lt;223>/modified Base = "2'·hydroxyl corresponding nucleotide" &lt;400> 447 cauugaccaa ggaaaucggt t 21 &lt;210> 448 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1, 15, 18 &lt;223&gt; / modified base = "2'-deoxy-2 '-Fluorine corresponding nucleotides&lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt; 〉 modified—base &lt;222>2, 3,4,5, 6,7, 8, 9,10, 11,12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid &lt;400> 448 ccgauuuccu uggucaaugt t 21 &lt;210&gt; 449 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA &lt;220&gt;&lt;221&gt; modified base -249- 152219. Sequence Listing.doc 201130494 &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4,7, 8, 16, 17 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt ; &lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'- Phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt;222&gt; 2, 5, 6, 9, 10, 11, 12, 13, I4t 15, 18, &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 449 cauugaccaa ggaaaucggt t 21 &lt;210&gt; 450 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; Description of the sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221〉 modified-base &lt;222>1,2, 5, 6, 7,8,9, 10,11, 14,15,18 &lt;223>/modified base = "2' deoxygenation -2'-fluoro corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base == "5'·phosphorothioate thymidine" -250- 152219 · Sequence table.doc 201130494 &lt;220 &lt;221&gt; modified_base &lt;222>3, 4,12, 13, 16, 17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400> 450 ccgauuuccu uggucaaugt t 21 &lt;210&gt; 451 &lt;211> 21 &lt;212> DN A &lt; 213 > artificial sequence

&lt;220〉 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: missing 5'-Late base" &lt;220&gt;&lt;221> modified_base &lt;222>1,2,3, 8,10,13, 16 &lt;223>/modified base = "2'·0· The corresponding nucleotide of thiol group &lt;220> &lt;221> modified_base &lt; 223> / modified base = "5' · phosphorothioate thymidine" &lt;220> &lt;221> modified a base &lt; 222>4, 5,6,7, 9, 11,12,14,15,17, 18, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 451 cccaggacau Gauaauaagt t 21 &lt;210&gt; 452 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence 251 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense of dsRNA Stock &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt; 222>2,3, 5, 6, 8, 9 &lt;223>/modified base = 2'-0-thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt ; &lt;221&gt; modified_base &lt;222>1, 4,7, 10, 11, 12, 13,14, 15, 16,17, &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid &lt;400> 452 cuuauuauca uguccugggt t 21 &lt;210&gt; 453 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1, 2,3,8, 10, 13,16 &lt;223>/modified base = "2M> thiol corresponding nucleotide" -252 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221 〉 modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4,5, 6,7, 9 , 11,12,14, 15, 17,18,19 &lt;223>/modified test base = " 2'-hydroxy corresponding nucleotide" &lt;400> 453 cccaggacau gauaauaagt t 21

&lt;210> 454 &lt; 211 &gt; 211 &gt; 212 &gt; 212 &gt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>2,3,5,6, 8, 9 &lt;223&gt;/modified base = "2'-deoxy-2'·fluoro corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-Thiophosphate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,4, 7, 10, 11, 12, 13, 14,15,16, 17, &lt; 223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 454 cuuauuauca uguccugggt t 21 -253 - 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 455 &lt;211> 21 &lt;212 〉 DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modi fied_ba.se &lt;222> 1 &lt;223>/modified Base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt; &l t;221〉 modified_base &lt;222>1, 2,3, 8, 10, 13, 16 &lt;223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220〉 &lt;;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>4, 5, 6, 7 , 9,11, 12, 14, 15,17, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 455 cccaggacau gauaauaagt t 21 &lt;210> 456 &lt;;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 -254- 152219·Sequence List.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,2,3 , 5,6,8,9 &lt;223>/modified base = "2^0-methyl corresponding nucleotide j &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/ Modified base = "5^ deuterated phosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base

&lt;222>4, 7,10, 11,12,13, 14,15,16,17,18, &lt;223>/modified base = "2:·hydroxy corresponding nucleotide" &lt;400&gt; 456 cuuauuauca uguccugggt t 21 &lt;210&gt; 457 &lt;211> 21 &lt;212> DNA <213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modifietl_ba.se &lt;222>1, 2, 3, 8, 10 , 13, 16 &lt; 223 &gt; / modified base = "25·0· thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'. Phosphorothioate thymidine" &lt;220> -255 - 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>4, 5, 6, 7, 9, 11, 12, 14, 15,17, 18, 19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 457 cccaggacau gauaauaagt t 21 &lt;210> 458 &lt;211> 21 &lt;212&gt ; DNA &lt; 213 > Artificial Sequence &lt; 220 > &lt; 223 > Description of Artificial Sequence: Antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; Modified_base &lt;222>1, 2, 3, 5, 6, 8, 9 &lt;223>/modified base = "2'-degassing-2, fluorine corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4,7, 10, 11, 12 , 13, 14, 15, 16, 17, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 458 cuuauuauca uguccugggt t 21 &lt;210> 459 &lt;211 〉 21 &lt;212&gt; DNA &lt; 213 > Artificial Sequence • 256- 152219 · Sequence Listing. doc 201130494 &lt; 220 > &lt; 223 > Description of Artificial Sequence: Sensed Strands of dsRNA &lt;220&gt;&lt;221&gt; modified_b ^se &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,2,3 , 8, 10, 13, 16 &lt;223>/modified base == "25-0 · thiol corresponding nucleus Glycosylation" &lt;220〉

&lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>4,5,6 , 7, 9, 11,12, 14,15, 17,18, &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 459 cccaggacau gauaauaagt t 21

&lt;210> 460 &lt; 211 &gt; 211 &gt; 21 I &lt;212> DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: antisense stock of dsRNA &lt; 220 &lt; 221 &gt; modified_ba. Se &lt;222>1,2,3,5,6, 8,9 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221〉 modified A base &lt;222> 21 &lt;223&gt; / modified base = "5: - thioate thymidine thymidine" -257 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified-base &lt;222>4, 7,10,11, 12,13,14,15, 16,17, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 460 ciiuauuauca uguccugggt t 21 &lt;210> 461 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt; 221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 8, 10,13,16 &lt;223>/modified base = "2'-0. thiol corresponding nucleoside &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>4 , 5, 6,7, 9,11, 12,14,15, 17,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 461 cccaggacau gauaauaagt t 21 &lt;210&gt; 462 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence -258 - 152219 · Sequence Listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2,3,5, 6,8,9 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleoside Acid &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉

&lt;221〉 modified-base &lt;222>4,7,10, 11, 12,13, 14, 15,16, 17,18, &lt;223>/modified base = "2'-hydroxy corresponding core "Glycosylation" &lt;400> 462 cuuauuauca uguccugggt t 21 &lt;210&gt; 463 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: meaning of dsRNA Stock &lt;220〉 &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221> modified-base &lt;222>1, 2, 3, 8, 10, 13, 16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified one Base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" -259- 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222&gt; 4,5, 6, 7, 9, 11,12, 14, 15,17, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 463 cccaggacau gauaauaagt t 21 &lt;210&gt; 464 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; artificial sequence &lt;220&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt ; &lt;221〉 modified-base &lt;222>1, 2, 3,5, 6, 8, 9,11, 13,14, 15,16 &lt;223>/modified base = "2' · go Gas·2'_Fluorine corresponding nucleotides&lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>4,7,10, 12, 17,18, 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 464

Cuuauuauca uguccugggt ΐ 21 &lt;210&gt; 46δ &lt;211> 21 &lt;212> DNA 260- 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: DsRNA Stocks &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide · lack of 5' phosphate group" &lt;220> &lt;221> modified_base &lt;;222>1,5,6,8,9, 10,12, 13,15 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide"

&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "55-thiolate thymidine" &lt;220&gt;&lt;221&gt; modified_ba,se &lt;222>2, 3, 4,7,11,14, 16,17, 18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 465 caaacuauuu gucgcaggat t 21

&lt;210> 466 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,9, 13, 18 -261 - 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7, 8, 10, 11,12, 14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 466 uccugcgaca aauaguuugt t 21 &lt;210> 467 &lt;211> 21 &lt;212 〉 DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "Nucleotide: Lack of 5'-phosphate group" &lt;220> &lt;22 1> modified_base &lt;222>1,5, 6,8, 9,10,12, 13,15 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220 〉 &lt;221&gt; iD〇dified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3 , 4, 7, 11, 14,16, 17, 18,19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 467 -262· 152219 - Sequence Listing.doc 201130494 caaacuauuu gucgcaggat t 21 &lt;210> 468 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 9, 13,18

&lt;223>/modified base = "2'-deoxy-2'_fluorine corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2,3,4,5,6, 7,8, 10,11, 12, 14, 15, 16, 17,19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 468 uccugcgaca aauaguuugt t 21 &lt;210&gt; 469 &lt;211> 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide : lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base •263 - 152219-sequence table.doc 201130494 &lt;222>1,5,6,8,9,10, 12,13,15 &lt ;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'- Phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 3, 4, 7 , 11, 14, 16, 17, 18, 19 &lt; 223 > / modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 469 caaacuauuu gucgcaggat t 21 &lt;210&gt; 470 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Base = "nucleotide: lack of 5'-decanoate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 9,13,18 &lt;223>/modified base = "2' -0-thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;;221〉 modified_base &lt;222>2, 3, 4, 5, 6,7,8, 10, 11,12, 14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid" -264- 152219 · Sequence Listing.doc 201130494 &lt;400> 470 uccugcgaca aauagiiuugt t 21 &lt;210> 471 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220〉 &lt;221〉 mo Dified one base

&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-decarboxylate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,5, 6, 8, 9,10, 12,13,15 &lt;223>/modified base == "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt ;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2,3, 4,7,11,14,16,17 , 18, 19 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 471 caaacuauuu gucgcaggat t 21 &lt;210&gt; 472 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> • 265 - 152219 - sequence listing.doc 201130494 &lt;221&gt; modified_base &lt;222>1,9, 13 , 18 &lt; 223 > / modified base = "2'-0 methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5 '-Thiophosphate thymidine &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6, 7,8,10,11,12, 14,15, &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 472 uccugcgaca aauaguuugt t 21 &lt;210> 473 &lt ;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223 〉/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; iuodificd_base &lt;222>1,5,6,8,9,10,12,13,15 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5' - phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>2, 3,4, 7, 11, 14,16, 17,18,19 &lt;223>/modified base = "2'. Hydroxy corresponding nucleotide" • 266· 152219 - Sequence Listing. doc 201130494 &lt;400&gt; 473 caaacuauuu gucgcaggat t 21 &lt;210&gt; 474 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt;&lt;220〉&lt;223> Description of artificial sequence: the inverse of dsRNA义股 &lt;220〉

&lt;221&gt; modified base <223> / modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,4,9,13 , 18 &lt; 223 > / modified base = "25 · deoxy-2 '-fluoro corresponding nucleotide" &lt; 220 > &lt; 221 > modified_base &lt; 222 > 21 &lt; 223 > / modified base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3,5, 6,7,8,10, 11, 12, 14,15,16, 〈 223&gt;/modified base = "2:-hydroxy corresponding nucleotide" &lt;400&gt; 474 uccugcgaca aauaguuugt t 21 &lt;210> 475 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA-sense stock-267- 152219·sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "Nucleotide: Lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1,5, 6,8,9,10, 12,13,15 &lt;223>/ Modified base = "2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221> mod Cated_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3,4, 7, 11, 14, 16, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 475 caaacuauuu gucgcaggat t 21 &lt;210&gt; 476 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222>1,4,9,13, 18 &lt;223>/modified base = "2'·degassing-2'·fluorine corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-Thiophosphate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,3,5,6, 7, 8,10, 11, 12,14,15, - 268- 152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 476 uccugcgaca aauaguuugt t 21 &lt;210&gt; 477 &lt;211> 21 &lt; 212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence : sRNA's sensible stock

&lt;221&gt; modified_b3se &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lacking 55·phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,5 ,6,8, 9,10, 12,13,15 &lt;223>/modified base == "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222 〉 21 &lt;223〉/modified base = "5'-phosphorothioate thymidine" &lt;221> modified-base &lt;222>2,3,4,7,11,14, 16,17, 18, 19 &lt;223>/modified base == "2'·hydroxy corresponding nucleotide" &lt;400> 477 caaacuauuu gucgca.ggat t 21 &lt;210> 478 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA • 269- 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221〉 modified_base &lt;222〉 1 &lt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,4, 9,13,18 &lt;223>/ Modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221&gt; _base &lt;222> 21 &lt;223>/modified base = "5'·depletion phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 5, 6, 7, 8,10,11, 12,14, 15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 478 uccugcgaca aauaguuugt t 21 &lt;210> 479 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; nj〇dified_base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>1, 5, 6,8, 9,10, 12, 13, 15 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; rnodified_base • 270· 152219 - Sequence Listing.doc 201130494 &lt;222> 21 &lt; 223>/modified base == "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,3,4,7,11, 14, 16,17 ,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 479 caaacuauuu Gucgcaggat t 21 &lt;210〉 480 &lt;211〉 21

&lt;212> DNA <213> Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222>1, 4, 9, 13, 18 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5' ·Thiophosphoryl thymidine

&lt;220&gt;&lt;221> modified-base &lt;222>2, 3, 5, 6, 7, 8, 10, 11, 12, 14, 15, &lt;223>/modified base = "2' -Hydroxy corresponding nucleotide" &lt;400&gt; 480 uccugcgaca aauaguuugt t 21 &lt;210> 481 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> -271 - 152219 - Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate &lt;220&gt;&lt;221> modified-base &lt;222>2, 4, 6, 8, 14, 17, 18 &lt;223>/modified base = "25-0-methyl corresponding nucleoside Acid &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified__base &lt;222&gt; 1, 3,5, 7, 9,10, 11, 12, 13,15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 481 guauguauaa agauagccat t 21 &lt;210&gt; 482 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220&gt;&lt;221&gt; aioclified^base &lt;222>1,5, 11,13,15, 17 &lt;223>/modified base = "2'·deoxy-2' -Fluorine corresponding nucleotides &lt;220> -272- 152219·SEQ ID NO.doc 201130494 &lt;221&gt; modified_ba.se &lt;222> 21 &lt;223>/modified base = "5'-thiophosphoric acid Ester thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3,4,6,7,8,9,10,12,14,16, 18, &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" &lt;400&gt; 482 uggcuaucuu uauacauact t 21 &lt;210&gt; 483 ^ &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220&gt;&lt;221&gt; modified_base

&lt;222>2, 4,6,8,14, 17, 18 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified one Base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,3,5, 7, 9, 10,11,12, 13, 15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 483 guauguauaa agauagccat t 21 -273 - 152219 · Sequence Listing .doc 201130494 &lt;210> 484 &lt;211> 21 &lt;212> DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: antisense strand of dsRNA &lt; 220 &lt; 221 &gt; Modified_base &lt;222>1,5,1], 13,15,17 &lt;223>/modified base = "25-deoxy-2'·fluorine corresponding nucleotide" &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 6, 7, 8,9,10, 12, 14, 16, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 484 Uggcuaucuu uauacauact t 21 &lt;210&gt; 485 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt;223 Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221 〉 modified_base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>2,4,6 , 8, 14,17,18 &lt;223>/modified base = "2:-0-methyl corresponding nucleotide" • 274-1522] 9-sequence table.doc 201130494 &lt;220〉 &lt;221&gt ; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,3, 5,7 , 9, 10, 11, 12, 13, 15, 16, 19 &lt; 223 > / modified base = = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 485 guauguauaa agauagccat t 21

&lt;210&gt; 486 &lt;211&gt; 21 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lacking 55·phosphate group" &lt;220&gt;&lt;221&gt; modified_base 9 &lt;222&gt; 1, 5, 11, 13, 15, 17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5' - phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>2, 3, 4,6,7, 8, 9,10, 12, 14, 16, 18, &lt;223>/ Modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 486 uggcuaucuu uauacauact t 21 -275 - 152219 · Sequence Listing.doc 201130494 &lt;210> 487 &lt;211> 21 &lt;212&gt; DNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-phosphate group" &lt;220〉 &lt;22 1&gt; raodified_base &lt;222>2,4, 6, 8, 14, 17,18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt ; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3,5, 7,9 ,10, 11,12, 13,15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 487 guauguauaa agauagccat t 21 &lt;210&gt; 488 &lt;211 〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222>1,5, 11, 13, 15, 17 &lt;223> human modified base = "2'·0-fluorenyl corresponding nucleotide" -276- 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222&gt 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>2, 3, 4, 6, 7, 8, 9, 10, 12, 14, 16, 18, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400〉 488 uggcuaucuu uauacauact t 21

&lt;210&gt; 489 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base ^ &lt;222&gt; 2, 4, 6, 8, 14, 17, 18 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/ Modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,3, 5, 7,9,10,11, 12,13, 15, 16, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 489 guauguauaa agauagccat t 21 -277- 152219-sequence table.doc 201130494 &lt;210> 490 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223&gt; Modified base = "nucleotide: lack of 5'-bowl acid ester group" &lt;220> &lt;22 1&gt; modified_base &lt;222>1,5, 11,13,15, 17, 19 &lt;223>/modified base = "2'·deoxy-2'-fluoro corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 6, 7,8,9,10, 12,14,16,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 490 uggcuaucuu uauacauact t 21 &lt;210〉 491 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; 213 > Artificial Sequence &lt; 220 &lt; 223 &gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt; 220 &lt; 221 &gt; 221 &gt; modified_base &lt; 222 &gt; 278·

152219·SEQ ID NO. doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'-acidate group" &lt;220> &lt;221> modified-base &lt;222>2,4, 6,8,14, 17,18 <223> / Modified base = "2'-0-mercaptonucleotide nucleotide" &lt;220&gt;&lt;221&gt; raodified_base &lt;222&gt; 21 &lt;223>/ Modified base == "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified-base • &lt;222&gt; 1, 3,5, 7,9,10,11, 12, 13 , 15, 16, 19 &lt; 223 > / modified base = "2s-hydroxy corresponding nucleotide" &lt;400> 491 guauguauaa agauagccat t 21 &lt;210> 492 &lt;211> 21 &lt;212> DNA &lt ;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;220&gt;&lt;221&gt; modified_base &lt;222>1,5, 11,13,15, 17,19 &lt;223>/modified base = "2'-deoxy-2'-fluoro corresponding nucleoside Acid &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;;222>2,3,4,6, 7, 8, 9,10,12,14,16, 18 &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400&gt; 492 • 279- 152219 - Sequence Listing. doc 201130494 uggcuaucuu uauacauact t 21 &lt;210&gt; 493 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: dsRNA Sensed stock &lt;220〉 &lt;221&gt; iaodified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modified_base &lt;;222>2, 4,6,8, 14, 17, 18 &lt;223>/modified base = "25-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222 〉 21 &lt;223〉/modified base = "55 · phosphorothioate thymidine" &lt;220 &lt;221&gt; modified_base &lt;222>1,3, 5,7, 9,10, 11, 12, 13, 15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400&gt; 493 guauguauaa agauagccat t 21 &lt;210&gt; 494 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 > artificial sequence &lt; 220 &lt; 223 &gt; 223 > description of artificial sequence: antisense stock of dsRNA ;220> &lt;221&gt; modified_base 280- 152219 · Sequence Listing.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;;221〉 modified-base &lt;222>1,5,11, 13,15,17,19 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220〉

&lt;221&gt; modified_base &lt;222>2,3,4,6,7, 8, 9,10, 12,14, 16, 18 &lt;223>/modified base = "2'·hydroxy corresponding nucleoside Acid &lt;400&gt; 494 uggcuaucuu uauacauact t 21 &lt;210&gt; 495 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA sine stock &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 2,4,6, 8,14,17,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "55·deuterated phosphate thymidine" -281 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified_base &lt;222>1,3, 5,7 , 9,10,11,12,13,15,16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 495 guauguauaa agauagccat t 21 &lt;210> 496 &lt;;211> 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&g t; &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; raodified_base &lt;222&gt;1,5,11,13,15, 17, 19 &lt;223&gt; Base = "25-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 3, 4, 6, 7, 8,9,10, 12,14,16,18 &lt;223>/modified base = "2' -Hydroxy corresponding nucleotide" &lt;400> 496 uggcuaucuu uauacauact t 21 &lt;210&gt; 497 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Sense stock of dsRNA &lt;220> -282 · 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate Base &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 4, 6,8,14,17,18 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified Base == "5' · phosphorothioate thymidine"

&lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 5,7,9, 10, 11, 12,13,15, 16, &lt;223>/modified base = "2'·hydroxyl Corresponding nucleotides &lt;400> 497 guauguauaa agauagccat t 21 &lt;210&gt; 498 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Antisense stock &lt;220> &lt;221> modified_base &lt;221>1,5, 9, 11,13, 15, 17 &lt;223>/modified base = "2'·0·methyl corresponding nucleoside Acid &lt;220> &lt;22]&gt; modifiedjbase &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt; 222>2,3,4,6, 7,8, 10,12,14,16,18, &lt;223>/modified base = "2^hydroxyl corresponding nucleotide" - 283 - 152219 - Sequence Listing .doc 201130494 &lt;400> 498 uggcuaucuu uauacauact t 21 &lt;210&gt; 499 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: meaning of dsRNA Stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Decorated base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>2,4,6, 8, 14, 17,18 &lt;223>/ Modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate Thymidine" &lt;220&gt;221&gt; modified_base &lt;222>1,3,5,7, 9,10,11, 12,13,15, 16, &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&lt;400&gt; 499 guauguauaa agauagccat t 21 &lt;210> 500 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence : antisense stock of dsRNA • 284- 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>1,5,10,11, 13,15,17 &lt;223>/modified base Base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220〉 &lt;221〉 modified-base &lt;222>2, 3,4,6, 7,8,9,] 2 14,16, 18, 19 &lt; 223> / = modified base "2 'hydroxy-corresponding nucleotide"

Uggcuaucuu uauacauact t 21 &lt;210&gt; 501 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt; <223> Description of artificial sequence: sRNA's sensible stock &lt;220&gt;

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>2, 4,6,8, 14,17,18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt; 223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,3, 5, 7, 9,10,11,12, 13, 15,16, •285 - 152219·SEQ ID NO:doc 201130494 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 501 guauguauaa agauagccat t 21 &lt;210> 502 &lt; 211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222>1, 5 ,9,10,11,13,15, 17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; m Odified_base &lt;222>2,3,4, 6,7, 8,12,14,16,18, 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400〉 502 uggcuaucuu uauacauact t 21 &lt;210&gt; 503 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-filler group" -286· 152219-sequence table.doc 201130494 &lt;220> &lt;221〉 Modified_base &lt;222>2, 3, 4, 5,6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt 220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'·deuterated phosphate thymidine" &lt;220> &lt;221> modified-base &lt;222 〉1,11, 13,14, 15, 16, 17,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide"

&lt;400&gt; 503 acucucuccu gugagaacat t 21 &lt;210> 504 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221&gt; modified_base 鲁&lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1,7,9, 19 &lt;223>/modified base = "2'-deoxy-2'·fluoro corresponding nucleotide" &lt;220> &lt;221&gt; modified-base &lt;222> 21 &lt;;223>/modified base = "55 · phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified a base • 287 · 152219 · Sequence Listing.doc 201130494 &lt;222> 2, 3, 4, 5, 6,8, 10, 11,12, 13,14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 504 uguucucaca ggagagagut t 21 &lt;210&gt ; 505 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;221&gt; raociified_ba.se &lt;222 〉 1 &lt;223>/modified base = " Glycoside: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3,4, 5,6, 7, 8, 9,10, 12, 18 &lt;223>/ Modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate Thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;221>1, 11,13,14, 15, 16, 17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400&gt; 505 acucucuccu gugagaacat t 21 &lt;210&gt; 506 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt; 288-152219-sequence table.doc 201130494 &lt;223&gt; Description: Antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,7,9,19 &lt;223>/modified base = "2s-de-氡-2'-fluorine corresponding core "Glycosylate" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'·thiolate thymidine" &lt;220> &lt;221〉 modified a base

&lt;222>2,3,4,5,6, 8,10,11,12,13,14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt; 400> 506 uguucucaca ggagagagut t 21 &lt;210> 507 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;221〉 Modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5; -carbonate group" &lt;220> &lt;221> modified-base &lt;222>2, 3, 4, 5,6,7, 8, 9, 10,12, 18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;;222> 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" &lt;220> -289- 152219-sequence table.doc 201130494 &lt;221&gt; modified_base &lt;222>1,11 , 13,14, 15, 16,17,19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 507 acucucuccu gugagaacat t 21 &lt;210&gt; 508 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: dsRNA Antisense stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt ;222&gt; 1, 7, 9, 19 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3,4, 5,6,8, 10,11, 12,13 , 14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 508 uguucucaca ggagagagut t 21 &lt;210> 509 &lt;211> 21 &lt;212&gt; DNA 〈 213&gt;Artificial sequence -290-1522丨9-sequence table, doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 <223&gt ; / Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 2, 3, 4, 5, 6, 7, 8, 9, 10 , 12, 18 &lt;223>/modified base = "2'-0·methyl corresponding nucleoside "&Lt; 220 &gt;

&lt;221〉 modified-base &lt;222> 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 13, 14, 15, 16, 19 &lt;223&gt; / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 509 acucucuccu gugagaacat t 21

&lt;210&gt; 510 &lt;211&gt; 21 ^ &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;;222>1,7, 9,19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223 〉/modified base = "55 · phosphorothioate thymidine" • 291 · 152219 - sequence listing.doc 201130494 &lt;220> &lt;221> modified_base &lt;222>2,3, 4, 5,6, 8,10, 11, 12, 13,14,15,16,17,18 &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 510 uguucucaca ggagagagut t 21 &lt;210&gt ; 511 &lt; 211 > 21 &lt; 212 > DNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt; 220 &gt; 221 > modified_base &lt; 222 &gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4, 5, 6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2'·0-methyl phase Nucleotide &lt;220&gt;221&gt; raodified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt; 222>1,11, 13,14,15,16,17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 511 acucucuccu gugagaacat t 21 &lt;210&gt; 512 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence-292-

152219·Sequence List.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222&gt; 1,3, 7,9, 19 &lt;223>/modified base = "2 '-Deoxy-2'-fluoro corresponding nucleotide" &lt;220&gt;&lt;221>modified-base&lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine &lt;220〉 &lt;221&gt; modified__base &lt;222>2,4,5, 6,8,10,11,12, 13,14,15, &lt;223>/modified base = "2^ hydroxyl Corresponding nucleotides &lt;400&gt; 〇12 uguucucaca ggagagagut t 21

&lt;210&gt; 513 &lt;211&gt; 21 Φ &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; Base &lt;222> 1 &lt;223&gt;/modified base == "nucleotide: lack of 5'-dicarboxylate group" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18 &lt;223>/modified base = "2'·0_ fluorenyl corresponding nucleotide" • 293 · 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt;222&gt; 1,11, 13, 14, 15, 16,17,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 513 acucucuccu gugagaacat t 21 &lt;210> 514 &lt;;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221> modified_base &lt;222>1, 3, 7, 9, 19 &lt;223>/modified base = "2'-deoxy-2s·fluoro corresponding nucleotide &lt;220&gt;221> modified base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; , 4, 5, 6, 8, 10, 11, 12, 13t 14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 514

Uguucucaca ggagagagut t 21 &lt;210&gt; 515 &lt;211> 21 &lt;212> DNA -294· 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: dsRNA Sensed stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;;222>2,3,4,5, 6,7,8, 9,10, 12,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide"

&lt;221〉 modified_base &lt;222&gt;21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&lt;221&gt; modified_base &lt;222>1, 11,13, 14, 15, 16, 17, 19 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 515 acucucuccu gugagaacat t 21

&lt;210> 516 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>1, 3,7,9,19 152219- Sequence Listing.doc -295 - 201130494 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>2,4,5,6,8,10,11,12,13 , 14, 15, 16 &lt; 223 > / modified base = = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 516 uguucucaca ggagagagut t 21 &lt;210&gt; 517 &lt;211&gt; 21 &lt;212〉 DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&g t; &lt;221〉 modified-base &lt;222>2, 3,4, 5,6, 7,8,9,10, 12,18 &lt;223>/modified base = "2'-0- Methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt; 221〉 modified—base &lt;222&gt; 1, 11, 13, 14, 15, 17, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 517 296 · 152219 - Sequence Listing.doc 201130494 acucucuccu gugagaacat t 21 &lt;210> 518 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense of dsRNA Stock &lt;220〉 &lt;221&gt; modified_base &lt;222>1,3,7,9,19

&lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = " 55-thiolate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 4,5,6,8,10, 11, 12,13,14, 15, 16, 17,17 &lt;223&gt;/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 518 uguucucaca ggagagagut t 21

&lt;210> 519 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400> 519 uguucgagga uaugacuga 19 &lt;210&gt ; 520 &lt; 211 > 19 • 297 · 152219 · Sequence Listing. doc 201130494 &lt; 212 &gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt;&lt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400> 520 ucagucauau ccucgaaca 19 &lt;210> 521 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 521 uucacuguac aaccgcagu 19 &lt;210&gt; 522 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 522 acugcgguug uacagugaa 19 &lt;210&gt; 523 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 523 ucucuucguu gacaaaa.ga 19 -298·

152219-Sequence List.doc 201130494 &lt;210&gt; 524 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 524 ucuuuuguca acgaagaga 19 &lt;210> 525 &lt;211> 19 φ &lt;212>瞧&lt;213>Artificial sequence&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 525 uaguaaaaug Ucuacccuc 19 &lt;210&gt; 526 &lt;211> 19 &lt;212&gt; RNA &lt;213> artificial sequence

&lt;220&gt; <223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 526 gaggguagac auuuuacua 19 &lt;210&gt; 527 &lt;211> 19 &lt;212> RNA <213>Artificial sequence &lt;220> 223&gt; Description of artificial sequence·· s. s. s. s. s. s. s. Sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 528 ugacgcaaga gucuucuga 19 &lt;210> 529 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt; 220> &lt;223> Description of artificial sequence: Sense strand of dsRNA &lt;400> 529 cgcuuuacuu uauaccuga 19 &lt;210&gt; 530 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 530 ucagguauaa aguaaagcg 19 &lt;210> 531 &lt;211&gt; 19 &lt;212> RNA &lt;213> artificial sequence • 300 152219 - Sequence Listing. 201130494 &lt;220〉 &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;40 0> 531 accagacuga uaauauaca 19 &lt;210&gt; 532 &lt;211> 19 &lt;212> RNA &lt;213&gt; artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;400> 532 uguauauuau cagucuggu 19 &lt;210> 533 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA sensible stock &lt;400&gt;; 533 aaagacagcc uguguucga 19

&lt;210> 534 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 534 ucgaacacag gcugucuuu 19 &lt;210&gt ; 535 &lt;211> 19 • 301 152219 · Sequence Listing. doc 201130494 &lt;212&gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; Cugugaagga uaguaaaau 19 &lt;210&gt; 536 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 536 auuuuacuau ccuucacag 19 &lt;210&gt; 537 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 537 uuuauugaca acacgcuuu 19 &lt;210&gt ; 538 &lt;211> 19 &lt;212> RNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Antisense Strand of dsRNA &lt;400&gt; 538 aaagcguguu gucaauaaa 19 -302 152219 - Sequence Listing .doc 201130494 &lt;210&gt; 539 &lt;211> 19 &lt;212&gt; RNA &lt;213&gt;&lt;220>&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 539 ccauaacaga auacccgag 19 &lt;210&gt; 540 &lt;211&gt; 19 φ &lt;212>dirty &lt;213>artificial sequence&lt; 220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 540 cucggguauu cuguuaugg 19 &lt;210&gt; 541 &lt;211> 19 &lt;212> RNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: Sense of dsRNA &lt;400&gt; 541 ucaaggaaau gauguuuau 19 &lt;210> 542 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA • 303 152219 · Sequence Listing. doc 201130494 &lt;400&gt; 542 auaaacauca uuuccuuga 19 &lt;210> 543 &lt;211> 19 &lt;212&gt; RNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 543 acuucacugu acaaccgca 19 &lt;210&gt; 544 &lt;211> 19 &lt;212> RNA &lt;213> artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 544 ugcgguugua cagugaagu 19 &lt;210&gt; 545 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 545 accgcaguaa uacggaaua 19 &lt;210&gt; 546 &lt;211> 19 &lt;212> RNA &lt; 213> artificial sequence 152219 - Sequence Listing. 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 54 6 uauuccguau uacugcggu 19 &lt;210> 547 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock

&lt;400&gt; 547 aaagugaucu cauauucuu 19 &lt;210> 548 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt;; 548 aagaauauga gaucacuuu 19

&lt;210> 549 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 549 aggaagauga ugcuuucaa 19 &lt;210 〉 550 &lt; 211 &gt; 19 - 305 152219 · Sequence Listing. doc 201130494 &lt;212&gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400 &gt; 550 Uugaaagcau caucuuccu 19 &lt;210&gt; 551 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 551 caaagaaagc cgccucaaa 19 &lt;210&gt; 552 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 552 uuugaggcgg cuuucuuug 19 &lt;210 〉 553 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 553 ugauguuuau ugacaacac 19 • 306 152219 · Sequence Listing .doc 201130494 &lt;210> 554 &lt;211> 19 &lt;212> RNA &lt;213> human procedure &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 554 guguugucaa uaaacauca 19 &lt;210&gt; 555 &lt;211&gt;21 @ &lt;212>leg&lt;213>artificial sequence&lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 555 uguucacucu cacuaacuu 19 &lt;210&gt; 556 &lt;211> 19 &lt;212> RNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 556 aaguuaguga gagugaaca 19 &lt;210> 557 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt ; &lt;223> Description of artificial sequence: Sense of stranded strands of dsRNA • 307 152219 - Sequence Listing.doc 201130494 &lt;400> 557 ggacaaagaa agccgccuc 19 &lt;210> 558 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213 〉Artificial sequence&lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400> 558 gaggcggcuu ucuuugucc 19

&lt;210&gt; 559 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sensed strand of dsRNA &lt;400&gt; 559 caaccgcagu aauacggaa 19 &lt;210 〉 560 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 560 uuccguauua cugcgguug 19 &lt;210> 561 &lt;;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence 308-

152219-Sequence List.doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence··sense stock of dsRNA&lt;4(8)&gt; 561 aagaaagccg ccucaaacc 19 &lt;210&gt; 562 &lt;211> 19 &lt;212&gt; RNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;400&gt; 562 gguuugaggc ggcuuucuu 19 &lt;210> 563 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt;; 563 aucucauauu cuuucagaa 19

&lt;210&gt; 564 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 564 uucugaaaga auaugagau 19 &lt;210 〉 565 &lt;211> 19 -309 152219 - Sequence Listing.doc 201130494 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; Auaacagaau acccgaggc 19 &lt;210> 566 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 566 gccucgggua uucuguuau 19 &lt;210&gt; 567 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 567 gccuguguuc gaggauaug 19 &lt;210 〉 568 &lt; 211 &gt; 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 > description of artificial sequence: antisense strand of dsRNA &lt;400> 568 cauauccucg aacacaggc 19 • 310 152219 - Sequence Listing .doc 201130494 &lt;210&gt; 569 &lt;211> 19 &lt;212> RNA &lt;213>Artificial Sequence &Lt;220>&lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 569 uuauugacaa cacgcuuua 19

&lt;210&gt; 570 &lt;211&gt; 19 • &lt;212&gt; RNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 570 uaaagcgugu ugucaauaa 19 &lt; 210> 571 &lt;211> 19 <212> RNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 571 acucucacua acuuacauc 19 &lt;210> 572 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt &lt;223> Description of artificial sequence: antisense strand of dsRNA-311 152219-sequence table.doc 201130494 &lt;400&gt; 572 gauguaaguu agugagagu 19 &lt;210&gt; 573 &lt;211> 19 &lt;212&gt; RNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 573 cugcaugauu uauagagua 19 &lt;210> 574 &lt;211> 19 &lt;212&gt; RNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 574 uacucuauaa aucaugcag 19 &lt;210> 575 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 575 ccgcaguaau acggaauau 19 &lt;210> 576 &lt;211> 19 &lt;212&gt; RNA &lt; 213> artificial sequence 1522丨9· Sequence Listing .doc 201130494 &lt;220〉 &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400〉 576 auauuccgua uuacugcgg 19 &lt;210&gt; 577 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA stocks

&lt;400&gt; 577 acaugcgccu ugugaugac 19 &lt;210&gt; 578 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt;; 578 gucaucacaa ggcgcaugu 19

&lt;210&gt; 579 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 579 uuccauaaca gaauacccg 19 &lt;210&gt ; 580 &lt; 211 > 19 • 313 · 152219 · Sequence Listing. doc 201130494 &lt; 212 &gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt;&lt; 223 &gt; 223 Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 580 cggguauucu guuauggaa 19 &lt;210&gt; 581 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213&gt;

&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 581 auacaaagug aiicucauau 19 &lt;210&gt; 582 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt ; &lt;223> Description of artificial sequence: antisense stock of dsRNA

&lt;400> 582 auaugagauc acuuuguau 19 &lt;210&gt; 583 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt;; 583 cagaagacuc uugcgucaa 19 -314· 152219 · Sequence Listing.doc 201130494 &lt;210&gt; 584 &lt;211> 19 &lt;212> RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: dsRNA Anti-sense stock &lt;400> 584 uugacgcaag agucuucug 19

&lt;210&gt; 585 &lt;211&gt; 19 | &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 585 uuccagaaag augauuagc 19 &lt;210&gt; 586 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213&gt;

&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 586 gcuaaucauc uuucuggaa 19 &lt;210> 587 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA - 315- 152219 - Sequence Listing. doc 201130494 &lt;400> 587 uaugacugau auugaucaa 19 &lt;210&gt; 588 &lt;211&gt; 19 &lt;212> RNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 588 uugaucaaua ucagucaua 19 &lt;210&gt; 589 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400> 589 ggcugcauga uuuauagag 19 &lt;210> 590 &lt;211> 19 &lt;212> RNA &lt; 213> artificial sequence &lt; 220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 590 cucuauaaau caugcagcc 19 &lt;210&gt; 591 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213> artificial sequence 316 152219 - Sequence Listing .doc 201130494 &lt;220〉 <223> Description of artificial sequence: sRNA's sensible stock &lt;400 591 ccgacuucac uguacaacc 19 &lt; 210 &gt; 592 &lt; 211> 19 &lt; 212> RNA &lt; 213> Artificial Sequence &lt; 220> &lt; 223> Description of Artificial Sequence of: dsRNA of antisense Unit

&lt;400&gt; 592 gguuguacag iigaagucgg 19 &lt;210&gt; 593 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;400&gt;; 593 auaguaaaau gucuacccu 19

&lt;210> 594 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 594 aggguagaca uuuuacuau 19 &lt;210&gt ; 595 &lt; 211 > 19 • 317 152219 - Sequence Listing. doc 201130494 &lt;212&gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; Ugacugauau iigaucaaag 19 &lt;210> 596 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 596 cuuugaucaa uaucaguca 19 &lt;210&gt; 597 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400> 597 cuugugauga ccucgccug 19 &lt;210&gt 598 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 598 caggcgaggu caucacaag 19 318·

152219·Sequence List.doc 201130494 &lt;210&gt; 599 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 599 ucga.ggauau gacugauau 19

&lt;210> 600 &lt;211&gt; 19 • &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 600 auaucaguca uauccucga 19 &lt; 210> 601 &lt;211> 19 &lt;212&gt; RNA &lt;213> artificial sequence

&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 601 gaugaccucg ccuguauuu 19 &lt;210> 602 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt ; &lt;223> Description of artificial sequence: antisense strand of dsRNA -319 152219-sequence table.doc 201130494 &lt;400&gt; 602 aaauacaggc gaggucauc 19 &lt;210> 603 &lt;211&gt; 19 &lt;212> RNA &lt;213 〉Artificial sequence&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400&gt; 603 agaguaaaca cguuuaumi 19 &lt;210&gt; 604 &lt;211> 19 &lt;212> RNA &lt;213> Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 604 aaauaaacgu guuuacucu 19 &lt;210&gt; 605 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 605 ccucucugug aaggauagu 19 &lt;210> 606 &lt;211> 19 &lt;212> RNA &lt;213> artificial sequence • 320·

152219·Sequence List.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 606 acuauccuuc acagagagg 19 &lt;210&gt; 607 &lt;211> 19 &lt;212&gt; RNA &lt; 213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA's sensible stock

&lt;400> 607 augauguuua uugacaaca 19 &lt;210> 608 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt;; 608 uguugucaau aaacaucau 19

&lt;210&gt; 609 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;400> 609 agacaacuuu ggccgacuu 19 &lt;210 〉 610 &lt; 211 &gt; 19 - 321 152219 - Sequence Listing. doc 201130494 &lt;212 > RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400> 610 Aagucggcca aaguugucu 19 &lt;210> 611 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA sine stock &lt;400> 611 uccauaacag aauacccga 19 &lt;210> 612 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 612 ucggguauuc uguuaugga 19 &lt;210&gt ; 613 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 613 guacaaccgc aguaauacg 19 -322

152219· Sequence Listing.doc 201130494 &lt;210> 614 &lt;211&gt; 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 &gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 614 cguauuacug cgguuguac 19

&lt;210&gt; 615 &lt;211> 19 • &lt;212> RNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; Description of artificial sequence · · dsRNA's sensible stock &lt;400> 615 ugauuagcac acaugcgcc 19 &lt ;210&gt; 616 &lt;211&gt; 19 &lt;212> RNA &lt;213>Artificial sequence

&lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 616 ggcgcaugug ugcuaauca 19 &lt;210> 617 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA - 323 152219 · Sequence Listing. doc 201130494 &lt;400> 617 augauuagca cacaugcgc 19 &lt;210> 618 &lt;211> 19 &lt;212&gt; RNA &lt;213 〉Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 618 gcgcaugugu gcuaaucau 19

&lt;210> 619 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA sine stock &lt;400> 619 gcuuuacuuu auaccugaa 19 &lt;210 〉 620 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 620 uucagguaua aaguaaagc 19 &lt;210&gt; 621 &lt;;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence •324·

1522丨9·Listing list.doc 201130494 &lt;220〉 &lt;223> Description of artificial sequence: Sense of dsRNA &lt;400> 621 ugcaugauuu auagaguaa 19 &lt;210> 622 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA

&lt;400&gt; 622 uuacucuaua aaucaugca 19 &lt;210> 623 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400 〉 623 cuuuggccga cuucacugu 19

&lt;210> 624 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 624 acagugaagu cggccaaag 19 &lt;210&gt ; 625 &lt; 211 > 19 • 325 152219 - Sequence Listing. doc 201130494 &lt;212 > RNA &lt; 213 > Artificial Sequence &lt; 220 > &lt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; Auccaccuga aaauauuga 19 &lt;210> 626 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 626 ucaauauuuu cagguggau 19 &lt;210> 627 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA's sensible stock &lt;400> 627 uguaa.uguuc acucucacu 19 &lt ;210> 628 &lt;211> 19 &lt;212> RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400> 628 agugagagug aacauuaca 19 -326·

152219-Sequence List.doc 201130494 &lt;210&gt; 629 &lt;211> 19 &lt;212> RNA &lt; 213 &gt; 213 &gt;&lt;220&gt;&lt; 223 &gt; 223 &gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 629 caccugaaaa uauugauga 19 &lt;210&gt; 630 &lt;211> 19 @ &lt;212>祖&lt;213>Artificial sequence&lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;400&gt; 630 ucaucaauau Uuucaggug 19 &lt;210> 631 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: sRNA sine stock &lt;400> 631 gacuucacug uacaaccgc 19 &lt;210> 632 &lt;211> 19 &lt;212> RNA &lt; 213> artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA • 327 152219 - sequence listing. doc 201130494 &lt;400&gt; 632 gcgguuguac agugaaguc 19 &lt;210&gt; 633 &lt;211> 19 &lt;212&gt; RNA &lt;213 〉Artificial sequence&lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;400> 633 uaacagaaua cccgaggcu 19

&lt;210&gt; 634 &lt;211> 19 &lt;212> RNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 634 agccucgggu auucuguua 19 &lt;210 〉 635 &lt; 211 &gt; 19 0 &lt; 212 &gt; RNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA &lt;400&gt; 635 aguaagagga cuggcugug 19 &lt;210> 636 &lt;211> 19 &lt;212> RNA &lt; 213 > artificial sequence 328 - 152219 - Sequence Listing. doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;400> 636 cacagccagu ccucuuacu 19 &lt;210> 637 &lt;211> 19 &lt;212&gt; RNA &lt; 213 &gt; artificial sequence &lt;220&gt;

&lt;223&gt; Description of artificial sequence: Sense strand of dsRNA &lt;400&gt; 637 aaccgcagua auacggaau 19 &lt;210&gt; 638 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220&gt; 〉 Description of artificial sequence: antisense stock of dsRNA &lt;400> 638 auuccguauu acugcgguu 19

&lt;210&gt; 639 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;400&gt; 639 ugucuacccu cuccuguaa 19 &lt;210&gt ; 640 &lt;211> 19 - 329- 152219 · Sequence Listing.doc 201130494 &lt;212&gt; RNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;400&gt; 640 uuacaggaga ggguagaca 19 &lt;210> 641 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA's sensible stock &lt;400> 641 gacaacuuug gccgacuuc 19 &lt;210&gt; 642 &lt;211> 19 &lt;212> RNA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; description of artificial sequence · antisense stock of dsRNA &lt;400&gt; 642 gaagucggcc aaaguuguc 19 &lt; 210> 643 &lt;211> 19 &lt;212> RNA &lt; 213> artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;400&gt; 643 gaauacccga ggcugcaug 19 -330 152219-preface List .doc 201130494 &lt;210&gt; 644 &lt;211> 19 &lt;212> RNA &lt;213>Artificial Sequence &l t; 220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 644 caugcagccu cggguauuc 19 &lt;210&gt; 645 &lt;211> 19 φ &lt;212>瞧&lt;213> artificial sequence&lt; 220> &lt;223> Description of artificial sequence: sRNA rational stock &lt;400> 645 acuuacauca. aaguuaggu 19 &lt;210&gt; 646 &lt;211> 19 &lt;212&gt; RNA &lt;213> artificial sequence

&lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 646 accuaacuuu gauguaagu 19 &lt;210&gt; 647 &lt;211&gt; 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA - 331 152219 - Sequence Listing.doc 201130494 &lt;400> 647 gauuagcaca caugcgccu 19 &lt;210&gt; 648 &lt;211> 19 &lt;212> RNA &lt;213 〉Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 648 aggcgcaugu gugcuaauc 19 &lt;210&gt; 649 &lt;211> 19 &lt;212&gt; RNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sense of dsRNA &lt;400&gt; 649 uuacaucaaa guuaggugg 19 &lt;210&gt; 650 &lt;211> 19 &lt;212&gt; RNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;400&gt; 650 ccaccuaacu uugauguaa 19 &lt;210&gt; 651 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence • 332 152219 - Sequence Listing .doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence: sRNA's sensible stock &lt ;220&gt;&lt;221〉 modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'·stearate group" &lt;220> &lt;221&gt; modified_base &lt;222> 1,3, 4,5, 11, 13, 16, 17 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt;

&lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,6, 7,8, 9,10, 12,14,15, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 651 uguucgagga uaugacugat t 21

&lt;210> 652 &lt;211> 21 • &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; Base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,6,8,18 &lt;;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" • 333 · 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223〉 / Modified base = "5'-thiophosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,3,4, 5,7,9, 10,11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 652 ucagucauau ccucgaacat t 21 &lt;210&gt; 653 &lt;211> 21 &lt;212> DNA &lt;213&gt; Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: missing 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3,5,6, 8, 10, 13,14, 16,19 &lt;223>/modified base = "25-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>4, 7,9, 11,12, 15, 17,18 &lt;223>/modified base == "2'·hydroxy corresponding nucleotide" &lt;400> 653 uucacuguac aaccgcagut t 21 -334· 152219 · Sequence Listing .doc 201130494 &lt;210> 654 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; Modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221〉modified_ba.se &lt;222>11,13 &lt;223&gt;/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;££1&gt; modified-base &lt;222> 21 &lt;223&gt;/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5, 6 , 7,8,9, 10,12, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 654 acugcgguug uacagugaat t 21 &lt;210&gt; 655 &lt;211 〉 21 &lt;212> DMA &lt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &gt;&lt; 223 &gt; Description of artificial sequence: sRNA suffix stock &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" - 335 - 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2, 3,4,5 , 6, 7, 9, 10, 13 &lt; 223 > / modified base = "2, 0 · methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt; / Modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_b Ace &lt;222>8,11, 12, 14, 15,16, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 655 ucucuucguu gacaaaagat t 21 &lt;210&gt; 656 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt;;222> 1 &lt;223>/modified base = "nucleotide: lacking 55-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 9 &lt;223>/modified base = "2'-〇-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221〉 modified one base •336·

152219·SEQ ID NO.doc 201130494 &lt;222>1, 2, 3,4,5,6,7,8, 10,11,12,13, &lt;223>/modified base = "2'-hydroxyl Corresponding nucleotides &lt;400&gt; 656 ucuuuuguca acgaagagat t 21 &lt;210&gt; 657 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Righteous stock

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,4, 9,11,12,13,15,16, 17, 18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;;222> 21 &lt;223>/modified base = "5'-thiophthalate thymidine"

&lt;221&gt; modified_base &lt;222&gt; 2, 3, 5, 6, 7, 8, 10, 14 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 657 uaguaaaaug Ucuacccuct t 21 &lt;210&gt; 658 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> - 337 - 152219 - Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: reverse of dsRNA义股&lt;220&gt;&lt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' decanoate group" &lt;220&gt;&lt;221&gt; Modified-base &lt;222>6, 10, 15, 18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1, 2, 3, 4, 5, 7 , 8, 9, 11, 12, 13, 14, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 658 gaggguagac auuuuacuat t 21 &lt;210&gt; 659 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description: Sensed Shares of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'·filling acid group" &lt;220 〉 &lt;221〉 modified-base &lt;222>1, 2, 9,10,11,12,13,15, 17,18 &lt;223>/modified base == "2'·0·methyl Corresponding nucleotides &lt;220> •338· 152219·SEQ ID NO.doc 201130494 &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-diaplated phosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 4, 5, 6, 7, 8, 14, 16, 19 &lt;223>/modified base = "1. hydroxyl corresponding nucleotide" &lt;;400&gt; 659 ucagaagacu cuugcgucat t 21 &lt;210> 660 I &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base

&lt;223&gt;/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 <223> / modified base = "5'- Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified-base &lt;222>1, 2,3,4,5, 7,8,9, 10, 11, 12, 13, . <223&gt; / Modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 660 ugacgcaaga gucuucugat t 21 •339· 152219-sequence table.doc 201130494 &lt;210&gt; 661 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nuclear Glycosidic acid: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>1, 3, 4, 5, 6, 8, 9,10,11, 13,15,16, 17 &lt ;223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5 '-Thiophosphate thymidine &lt;220〉 &lt;221&gt; modified_base &lt;222>2, 7, 12, 14, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 661 cgcuuuacuu uauaccugat t 21 &lt;210> 662 &lt;211> 21 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modifiedjbase &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5 '-Phosphate group> • 340- 152219-Sequence table.doc 201130494 &lt;220> &lt;221> modified_base &lt;222&gt; 2, 6, 8, 13 &lt;223>/modified base = "2'- 0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,3,4, 5, 7,9,10,11, 12,14, 15, 16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide "

&lt;400&gt; 662 ucagguauaa aguaaagcgt t 21 &lt;210&gt; 663 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221> modified_base &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>2,3, 7 , 8, 11, 14, 16, 18 &lt; 223 > / modified base = "2'-0 · methyl corresponding nucleotide" &lt; 220 > &lt; 221 > modified a base &lt; 222 > 21 &lt ;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,4,5,6, 9,10,12, 13 ,15,17,19 • 341 · 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base == "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 663 accagacuga uaauauacat t 21 &lt;210&gt; 664 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;;223>/modified base = "nucleotide: Less 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>3,5, 8, 11 &lt;223>/modified base = "2^0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5: - phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222> 1, 2, 4, 6, 7, 9, 10, 12, 13, 14, 15, 16, &lt;223>/modified base = "2; -hydroxy corresponding nucleotide" &lt;400&gt; 664 uguauauuau Cagucuggut t 21 &lt;210&gt; 665 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA -342 - 152219 - Sequence Listing. Doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>6, 9,10,11,13,15, 16, 17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine"

&lt;220〉 &lt;221〉 modified-base &lt;222&gt; 1, 2, 3, 4, 5, 7, 8, 12, 14, 18, 19 &lt;223>/modified base = "2'· Hydroxyl corresponding nucleotide" &lt;400&gt; 665 aaagacagcc uguguucgat t 21 &lt;210&gt; 666 &lt;211&gt; 21 &lt;212> DNA &lt;213&gt;

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: lack of 5'- Phosphate group" &lt;220> &lt;221> modified-base &lt;222> 6, 8 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220&gt;&lt;;221〉 modified-base - 343 - 152219· Sequence Listing.doc 201130494 &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; Modified_base &lt;222>1, 2,3,4,5, 7, 9, 10,11,12,13,14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt 400> 666 ucgaacacag gcugucuuut t 21 &lt;210&gt; 667 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA's sensible stock &lt;220&gt;;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2 , 4,11,14,19 &lt;223>/modified base = " 2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>3,5,6, 7,8, 9,10, 12, 13,15,16, 17, &lt;223>/modified base = "2'·hydroxy corresponding Nucleotide &lt;400&gt; 667 cugugaagga uaguaaaaut t 21 &lt;210&gt; 668 • 344· 152219· Sequence Listing.doc 201130494 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220> &lt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222> 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt ;220〉

&lt;221〉 modified-base &lt;222>5,8,15,17 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220〉 &lt;221〉 modified —base &lt;222〉 21 &lt;223〉/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3, 4,6 ,7,9,10, 11,12, 13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 668 auuuuacuau ccuucacagt t 21

&lt;210&gt; 669 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> -345 - 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222 〉1, 2, 3, 5, 6, 9,12, 14,16,17,18,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt ; &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>4, 7,8, 10, 11, 13, 15 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 669 uuuauugaca acacgcuuut t 21 &lt;210&gt; 670 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA

&lt;220X &lt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221&gt; modified_base &lt; 222>13, 16 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base Base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3, 4, 5,6,7, 8,9, 10,11,12, 14, &lt;223>/modified base = "2s-hydroxy corresponding nucleotide" -346- 152219 · Sequence Listing.doc 201130494 &lt;400> 670 aaagcguguu gucaauaaat t 21 &lt;210> 671 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified base

&lt;223&gt;/modified base = "nucleotide: lack of 5'-obstructive acid group" &lt;220&gt;&lt;221> modified-base &lt;222>1,2, 4,7, 12, 14 , 15, 16 &lt; 223 > / modified base = "2'-0_ fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221>modified_base &lt;222>3,5, 6,8,9, 10, 11,13,17, 18,19 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 671 ccauaacaga auacccgagt t 21 &lt;210> 672 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA -347-152219 · Sequence Listing.doc 201130494 &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221>mociified_base&lt;222>7, 15 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleoside Acid &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2, 3, 4, 5,6, 8,9, 10, 11,12,13, &lt;223&gt;/modified base = "2'. hydroxyl corresponding nucleotide" &lt;400&gt; 672 cucggguauu cuguuauggt t 21 &lt;210&gt; 673 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt;&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: lack of 5 '-Phosphate group> &lt;220> &lt;221> modified-base &lt;222>1,2,10,13,15, 16,17, 19 &lt;223>/modified base = "2'- 0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 348- 152219-sequence table.doc 201130494 &lt;223>/modified base = "5'-phosphorothioate Thymidine" &lt;220&gt;221&gt; modified_base &lt;222>3, 4,5,6,7, 8,9,11,12, 14, 18 &lt;223>/modified base = "2' -hydroxy corresponding nucleotide" &lt;400&gt; 673

Ucaaggaaau gauguuuaut ΐ 21 &lt;210&gt; 674 &lt;211> 21 &lt;212&gt; DNA

&lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 55-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,6,9 &lt;223>/modified base = "2'-0-methyl corresponding core &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222 〉1, 3,4,5,7, 8, 10,11,12,13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 674 auaaacauca uuuccuugat ΐ 21 &lt;210&gt; 675 &lt;211> 21 349- 152219 - Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sensed Shares of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222&gt; 2,3, 4,5,7, 8,10, 12, 15,16 , 18 &lt; 223 > / modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = " 5'-Thiophosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,6, 9,11, 13, 14, 17, 19 &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&lt;400&gt; 675 acuucacugu acaaccgcat ΐ 21 &lt;210&gt; 676 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; : Antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of phosphate group" &lt;220> &lt;221&gt; modified_base - 350·

1522丨9-Sequence List.doc 201130494 &lt;222> 9, 11 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified a base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2,3,4,5 ,6,7,8,10,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 676

Ugcgguugua cagugaagut t 21 &lt;210&gt; 677 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt;&lt;223&gt; Description of artificial sequence: sRNA's sensible stock &lt;220&gt; 〉 modified_base &lt;222〉 1 &lt;223>/modified base = "nucleotide: lack of 5' disc acid ester group" &lt;220&gt;&lt;221> modified-base &lt;222>2, 3, 5,8,11, 13, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; /modified base == "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,4,6,7, 9, 10, .12,14, 15, 16, 17, &lt;223>/modified base = "2s-hydroxy corresponding nucleotide" • 351 - 152219 · Sequence Listing. doe 201130494 &lt;400&gt; 677 accgcaguaa uacggaauat t 21 &lt;210&gt; 678 &lt;211 〉 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/ Modified base = "nucleotide: missing 5'- Acidate group &lt;220> &lt;221&gt; modified_base &lt;222>1,8,11 &lt;223>/modified base = "2'-0 thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5^ phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 3, 4, 5, 6 , 7, 9, 10,12,13, 14,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" <Current> 678 uauuccguau uacugcggut t 21 &lt;210&gt; 679 &lt ;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> -352· 152219 · Sequence Listing.doc 201130494 &lt;221&gt ; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'·stearate group" &lt;220> &lt;221&gt; modified_base &lt;222>5, 8,9, 10,11, 13, 15, 16, 17,18,19 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222 〉 21 &lt;223〉/modified base = "5'·deuterated phosphate thymidine"

&lt;221〉 modified-base &lt;222>1, 2,3, 4, 6,7,12, 14 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 679 aaagugaucu cauauucuut t 21 &lt;210&gt; 680 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;〇&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lacking 55 · cleavage ester group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 6, 14 &lt; 223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5' - thioate thymidine thymidine" - 353 - 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 2,3, 4,5,7, 8, 9,10, 11,12,13, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 680 aagaauauga gaucacuuut t 21 &lt;210> 681 &lt;211> 21 &lt;212> DNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: d Sense of sRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; Modified_base &lt;222&gt; 8, 11, 13, 14, 15, 17 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2,3,4,5,6 , 7, 9, 10, 12, 18, 19 &lt; 223 > / modified base = "25 · hydroxyl corresponding nucleotide" &lt; 400 > 681

Aggaagauga ugcuuucaat t 21 &lt;210&gt; 682 &lt;211> 21 &lt;212> DNA -354- 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: dsRNA Antisense stock &lt;220> &lt;221>modified one ba.se &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 8, 11 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide"

&lt;221&gt; modified_base &lt;222> 21 &lt;223&gt; / modified base = "5'_ phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 4,5,6,7,9, 10, 12, 13,14, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 682 uugaaagcau caucuuccut t 21

&lt;210&gt; 683 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1' 10, 11, 13, 14 , 15, 16 -355 - 152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; rnodified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4, 5, 6, 7, 8, 9 , 12, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 683 caaagaaagc c.gccucaaat t 21

&lt;210&gt; 684 &lt;211> 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1.·19 &lt;223>/经^(Activating base = "2'-hydroxy corresponding nucleotide &lt;400&gt; 684 uuugaggcgg cuuucuuugt t 21 &lt;210&gt; 685 &lt;211> 21 -356-

1522]9·Sequence List.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;221&gt; modified_base &lt;222 〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate base" &lt;220> &lt;221> modified_base

&lt;222>1,4,6,7,8,10,11,14,17,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'·thiolate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3 , 5,9, 12, 13, 15,16,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 685 ugauguuuau ugacaacact t 21 &lt;210> 686 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt; 223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220&gt;&lt;221&gt; modified_base • 357· 152219·sequence table.doc 201130494 &lt;222>8,11, 15 , 18 &lt; 223 > / modified base = "2'-0 · methyl corresponding nucleotide" &lt; 220 > &lt; 221 > modified_base &lt; 222 > 21 &lt; 223 > / modified base = " 5'-Thiophosphate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>1,2,3 , 4, 5, 6, 7, 9, 10, 12, 13, 14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 686 guguugucaa uaaacaucat t 21 &lt;210&gt; 687 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-steanate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3,4,5,7,8, 9, 10, 11, 13, 14, 17, &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;;223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2,6,12, 15, 16 &lt;223>/ Modified base = "2'-hydroxyl corresponding nucleotide" -358- 152219 · Sequence Listing.doc 201130494 &lt;400> 687 uguucacucu cacuaacuut t 21 &lt;210> 688 &lt;211> 21 &lt;212> DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;22 0〉

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of V-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>5,18 &lt; 223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5' - phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base &lt;222>1,2,3,4, 6,7, 8,9, 10,11,12,13, &lt;223 〉/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 688 aaguuaguga gagugaacat t 21 &lt;210&gt; 689 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt; -359- 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = " Nucleotide: lack of 5'-filler group" &lt;220> &lt;221> modified-base &lt;222>4, 13, 14, 16, 17,18,19 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220〉 &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3,5, 6,7 , 8,9,10,11,12,15 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 689 ggacaaagaa agccgccuct t 21 &lt;210&gt; 690 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_ba.se &lt;222> 1 &lt;223&gt; / Modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5' · hypophosphorous acid Ester thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" -360-

152219-Sequence List.doc 201130494 &lt;400> 690 gaggcggcau ucuuugucct t 21 &lt;210&gt; 691 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sense stock of dsRNA &lt;220〉 &lt;221〉 modified-base 鲁&lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;;221〉 modified-base &lt;222>1,4,5,7,10, 13, 15 <223> / modified base == "25-0-thiol corresponding nucleotide" &lt;220〉 &lt;;221〉 modified-base &lt;222> 21 &lt;223>/modified base == "5'·phosphorothioate thymidine" &lt;220〉

&lt;221〉 modified-base &lt;222>2,3,6,8,9, 11,12,14, 16,17,18, &lt;223>/modified base = "25·hydroxy corresponding nucleoside Acid &lt;400&gt; 691 caaccgcagu aauacggaat t 21 &lt;210&gt; 692 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense stock of dsRNA • 361 · 152219· Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of phosphate group" &lt;220> &lt; 221> modified_base &lt;222>6,9 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223 〉/modified base = "5'· phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3,4, 5,7,8, 10, 11, 12 , 13,14, &lt;223> human modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 692 uuccguauua cugcgguugt t 21 &lt;210> 693 &lt;211> 21 &lt;212> DNA &lt ;213>Artificial sequence &lt;220> &lt;223> human procedure Description of column: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221〉 modified-base &lt;222>8, 9, 11, 12, 13, 14, 18, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;;220>&lt;221&gt; modified_base &lt;222> 21 •362· 152219·sequence table.doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt; 221〉 modified—base &lt;222>1,2, 3, 4, 5, 6,7,10,15,16,17 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 693

Aagaaagccg ccucaaacct t 21 &lt;210&gt; 694 &lt;211> 21 &lt;212> DNA

&lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nuclear Glycoside: lack of 55·phosphate group” &lt;220> &lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉 &lt;;221&gt; modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 694 gguuugaggc ggcuuucuut t 21 &lt;210&gt; 695 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed stock of dsRNA • 363 · 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 1 · &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221&gt; modified_base &lt;222>2,3, 4, 5, 7,9,10, 11, 12,13, 14, 15 &lt;223>/modified base == "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt; 222> 21 &lt;223〉/modified Base = "5'-deuterated phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 6,8,16,17,18,19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 695 aucucauauu cuuucagaat t 21 &lt;210> 696 &lt;211> 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220> &lt;223&gt; Description: Antisense strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lacking 55·phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 12 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base -364- 152219-sequence table" 201130494 &lt;222> 21 &lt;223>/modified base 5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3, 4,5,6, 7,8,9,10, 11,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 696 uucugaaaga auaugagaut t 21

&lt;210&gt; 697 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>2, 5, 10, 12, 13, 14 , 19 &lt; 223 > / modified base = "2' · 0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = " 5'·Thiophosphate thymidine” &lt;220> &lt;221> modified-base &lt;222>1,3,4,6,7,8,9,11,15,16,17, &lt;223 〉/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 697 auaacagaau acccgaggct t 21 &lt;210&gt; 698 365 - 152219 · Sequence Listing.doc 201130494 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nuclear Glycosidic acid: lack of 5'-decanoate group" &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 9, 17 &lt;223&gt; / modified base = "2'-0. thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2, 3, 4, 5, 6, 7, 8 , 10,11, 12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 698 gccucgggua uucuguuaut t 21 &lt;210> 699 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> -366- 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222>2, 3, 4, 6, 8, 9, 10 ,16,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-thiophthalate thymidine" &lt;220&gt;&lt;221〉 modified_base &lt;;222>1,5,7, 11,12, 13, 14,15,17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400> 699 gccuguguuc gaggauaugt t 21 &lt;210> 700 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 3, 13, 15 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base Base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 4,5, 6,7,8, 9,10,11,12, 14, 16, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -367- 152219 - Sequence Listing.doc 201130494 &lt;400> 700 cauauccucg aacacaggct t 21 &lt;210> 701 &lt;211〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Modified base = "nucleotide: missing 5'- Phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,4,5, 8,11, 13, 15, 16,17, 18 &lt;223>/modified base = "2 '·0-methyl corresponding nucleotides &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>3, 6, 7, 9,10, 12, 14, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 701 uuauugacaa Cacgcuuuat t 21 &lt;210> 702 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA•368·

152219-Sequence List.doc 201130494 &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'·dish acid ester group" &lt;220&gt;;&lt;221〉 modified-base &lt;222>1, 14, 17 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine"

&lt;221〉 modified_base &lt;222>2, 3, 4,5, 6,7, 8,9,10, 11, 12, 13, &lt;223>/modified base = "2'-hydroxy corresponding core "Glycosylation" &lt;400> 702 uaaagcgugu ugucaauaat t 21 &lt;210&gt; 703 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt;

&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' · Phytate base" &lt;220> &lt;221> modified-base &lt;222>2, 3, 4, 5, 6, 8, 9, 12, 13, 14, 16, 18, &lt;223>/ Modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 -369- 152219-sequence table.doc 201130494 &lt;223>/ Modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,7, 10, 11,15,17 &lt;223>/modified base = " 2'·hydroxyl-related nucleotides &lt;400&gt; 703 acucucacua acuuacauct t 21 &lt;210&gt; 704 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Artificial sequence Description: Antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 <223&gt; / modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>5,10 &lt;223&gt;/modified base = "25-0-thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt; 220> &lt;221&gt; modified_base &lt;222>1,2,3,4,6, 7, 8,9, 11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxyl Corresponding nucleotides &lt;400&gt; 704 gauguaaguu agugagagut t 21 &lt;210&gt; 705 &lt;211&gt; 21 370·152219·SEQ ID NO. doc 201130494 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lacking 55·phosphate group" &lt; 220> &lt;221〉 modified-base &lt;222>1,2,4,6,9, 10,11, 13, 18

&lt;223>/modified base == "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5 '·Thionothioate thymidine>> &lt;220> &lt;221> modified-base &lt;222>3,5,7,8, 12,14, 15,16, 17,19 &lt;223>/modified Base = "2'-hydroxyl corresponding nucleotide" &lt;400> 705 cugcaugauu uauagaguat t 21

&lt;210&gt; 706 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of acid ester group" &lt;220&gt;&lt;221> modified_base -371 · 152219 - sequence table.doc 201130494 &lt;222>1 , 6, 8, 13, 17 &lt; 223 > / modified base = "2' · 0 · thiol corresponding nucleotide" &lt; 220 > &lt; 221 > modified a base &lt; 222 &gt; 21 &lt; 223 〉/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3,4,5,7,9, 10,11,12, 14 , 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 706 uacucuauaa aucaugcagt t 21 &lt;210> 707 &lt;211> 21 &lt;212> DNA &lt;213 〉Artifical sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: Lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; Modified_base &lt;222>1, 2,4,7,10, 12, 17, 19 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>3,5,6, 8,9 , 11, 13,14,15, 16,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" -372· 152219 · Sequence Listing.doc 201130494 &lt;400> 707 ccgcaguaau acggaauaut t 21 &lt;210> 708 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base

&lt;223&gt;/modified base = "nucleotide: lacking 55-filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt;2,9,12 &lt;223&gt; = "2M&gt; methyl corresponding nucleotide" &lt;220&gt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221〉 modified-base ^ &lt;222&gt; 1, 3, 4, 5, 6, 7, 8, 10, 11, 13, 14, 15, &lt;223>/modified base = "2'- Hydroxyl corresponding nucleotide" &lt;400> 708 auauuccgua uuacugcggt t 21 &lt;210> 709 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: dsRNA Right stock &lt;220> • 373 · 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,4, 6,8,9, 10, 11, 13, 16, 19 &lt;223>/modified base = "2'·0·A Corresponding nucleotides &lt;220> &lt;221&gt; modified_ba.se &lt;222> 21 &lt;223>/ Modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 3, 5, 7, 12, 14, 15, 17, 18 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 709 acaugcgccu ugugaugact t 21 &lt;210> 710 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221 &gt; modified_ba*se &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5;- Phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3,6,8,15 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt ; &lt;221〉 modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" -374 -

152219-Sequence table.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>1,2,4, 5,7,9,10,11, 12,13,14, 16, &lt;223>/ Modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 710 gucaucacaa ggcgcaugut t 21 &lt;210> 711 &lt;211> 21 &lt;212> DNA &lt; 213> artificial sequence • &lt;220> &lt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;;220&gt;&lt;221〉 modified-base &lt;222>1,2,3,4,6,9,14,16,17,18 &lt;223>/modified base = "2'-0-曱Base corresponding nucleotide" &lt;220〉

&lt;221〉 modified-base &lt;222> 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>5, 7,8 ,10, 11,12,13, 15,19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400&gt; 711 uuccauaaca gaauacccgt t 21

&lt;210&gt; 712 &lt;211&gt; 21 &lt;212&gt; DNA - 375 - 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA ;220&gt;&lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt; 222>5,13 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3, 4,6, 7,8,9, 10,11,12, 14, &lt;223>/modified base = "2^hydroxyl corresponding nucleotide" &lt;400&gt; 712 cggguauucu guuauggaat t 21 &lt;210> 713 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt;213&gt;;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 <223&gt; / modified base == "nucleotide: lack of 5' Filling base" &lt;220&gt;&lt;221〉 mo Dified—base &lt;222>2, 4, 9, 12, 13, 14, 15, 17, 19 152219-sequence table.doc -376- 201130494 &lt;223>/modified base = "2'-0- Methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,3,5,6, 7,8,10, 11, 16, 18 &lt;223>/modified base = "Γ-hydroxy corresponding nucleotide" &lt;400> 713 Auacaaagug aucucauaut t 21

&lt;210> 714 &lt;211&gt;21 &lt;212&gt;212&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group"

&lt;221&gt; modified_base &lt;222&gt; 2, 10, 17 &lt;223&gt;/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1, 3, 4, 5, 6, 7, 8 , 9, 11, 12, 13, 14, &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 714 • 377- 152219-sequence table.doc 201130494 auaugagauc acuuuguaut t 21 &lt ;210&gt; 715 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt ; 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 8, 9, 10, 11, 12, 14, 16,17 &lt;223>/modified base = "2'-0. methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_ba.se &lt;222&gt; 21 &lt;223&gt; Modified base = "5'-phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &Lt;222>2, 3,4, 5,6, 7, 13,15,18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 715 cagaagacuc uugcgucaat t 21 &lt;210&gt; 716 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; One base -378-

152219-Sequence List.doc 201130494 &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 7 &lt;;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 <223> / modified base = "5' - phosphorothioate thymidine" &lt;220> &lt;221>modified-base &lt;222>1,2,3,4,5, 6,8,9,10,11, 12,13, &lt;223 〉/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 716 uugacgCELag agucuucugt t 21 &lt;210> 717 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220 〉

<223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221> modified_base &lt;222>1,2,3, 4, 12, 15,16,19 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide &lt;220〉 &lt;221> modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" • 379- 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>5,6, 7, 8, 9,10,11, 13, 14, 17,18 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 717 uuccagaaag augauuagct t 21 &lt;210> 718 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 3, 7 &lt;223>/modified base = "2'-0· Corresponding nucleotides &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-stealing thymidine j &lt; 220> &lt;221&gt; Modified_base &lt;222>1,2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt 400> 718 gcuaaucauc uuucuggaat t 21 &lt;210> 719 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence 380 - 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence : sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt ; modified_base &lt;222>1, 3,6,7,10, 12,13,16, 17 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220〉

&lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base == "5'·phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2, 4 , 5, 8, 9,11, 14,15, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 719 uaugacugau auugaucaat t 21 &lt;210&gt; 720 &lt;211&gt; 21 &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 &gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified-base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>6,9,12, 16,18 &lt;223>/modified base Base = "2'-0·methyl corresponding nucleotide" -381 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221〉 modified_base &lt;222&gt; 21 &lt;223>/modified base = " 5'-Thiophosphate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,2, 3,4, 5,7, 8,10,11, 13,14, 15, &lt;223 〉/modified base = "2'·hydroxy corresponding nucleotide" &lt;400〉 720 uugaucaaua ucagucauat t 21 &lt;210&gt; 721 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>3, 4, 6, 8, 11, 12, 13, 15 &lt;223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base Base = "5'-thiophosphate thymidine" &lt;220> &lt;221> modified_base &lt;222&gt; 1, 2, 5, 7, 9, 10, 14, 16, 17, 18, 19 &lt;223 〉/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 721 ggcugcauga uuuauagagt t 21 -382 - 152219 - sequence listing.doc 201130494 &lt;210> 722 &lt;211> 21 &lt;212〉 DNA <213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nuclear Glycosidic acid: lack of 5'-phosphate group

&lt;220〉 &lt;221&gt; modified_base &lt;222>4,6, 11, 15 &lt;223>/modified base = "2'·0· thiol corresponding nucleotide" &lt;220> &lt;221&gt ; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>1, 2, 3, 5, 7 , 8, 9, 10,12,13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" φ &lt;400&gt; 722 cucuauaaau caugcagcct t 21 &lt;210> 723 &lt; 211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222> 1 - 383 - 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 5, 6 , 7,8,10,11, 13, 15, 18, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt; &l t;221&gt; modified_base &lt;222>3, 4,9,12,14,16,17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 723 ccgacuucac uguacaacct t 21 &lt;210> 724 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate base" &lt;220> &lt;221&gt; modified_base &lt;222>6,8 &lt;223>/ Modified base = "2'-0-thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate chest Glycoside &lt;220&gt; -384-

152219-Sequence table.doc 201130494 &lt;221&gt; mod ifi ed_bas e &lt;222>1,2, 3, 4, 5, 7, 9,10,11,12, 13, 14, &lt;223>/modified Base = "2'-hydroxy corresponding nucleotide" &lt;400> 724 gguuguacag ugaagucggt t 21 &lt;210&gt; 725 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> $ &lt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt ;220&gt;<221&gt; modified-base &lt;222>2, 5, 10, 12, 13, 14, 16, 17, 18, 19 &lt;223>/modified base = "2'-0-methyl Corresponding nucleotides &lt;220〉 &lt;221〉 modified-base

&lt;222> 21 <223> / modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,3,4, 6,7,8 , 9, 11, 15 &lt; 223 > / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 725 auaguaaaau gucuacccut t 21 &lt;210> 726 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; 213 artificial sequence 385 - 152219 - Sequence Listing. doc 201130494 &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 〉/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>5, 9, 14,17 &lt;223>/modified base Base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "y-phosphorothioate thymidine &lt;220〉 &lt;221> modified-base &lt;222>1, 2, 3, 4,6, 7, 8,10, 11, 12, 13,15, &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 726 aggguagaca uuuuaciiaut t 21 &lt;210> 727 &lt;21 1> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1,4, 5,8, 10, 11, 14, 15 &lt;223>/modified base = "25-0-thiol corresponding nucleotide" -386· 152219-sequence table.doc 201130494 &lt;220〉 &lt;221&gt; modified a base &lt;222> 21 &lt;;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>2,3,6,7,9,12, 13, 16, 17, 18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 727 ugacugauau ugaucaaagt t 21 ^ &lt;210&gt; 728 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nuclear Glycosidic acid: lack of 5'-phosphate group" &lt;220〉

&lt;221〉 modified-base &lt;222>8,11,14,18 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1,2,3,4, 5, 6 , 7, 9, 10, 12, 13, 15, &lt;223>/modified base = "25. hydroxyl corresponding nucleotide" &lt;400&gt; 728 cuuugaucaa uaucagucat t 21 • 387· 152219 - Sequence Listing. 201130494 &lt;210&gt; 729 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,5,8, 11,12, 13,14,16,17, &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt; 221〉 modified-base &lt;222>4, 6, 7,9,10, 15, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 729 cuugugauga ccucgccugt t 21 &lt;210> 730 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified one Base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" • 388 - 152219. Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt; 222>1,11, 14,16 &lt;223>/modified base = "2'-0.methyl corresponding nucleotide" &lt;220> 1 &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223 〉/modified base = "5'· phosphorothioate thymidine" &lt;220〉 &lt;221> modified_base &lt;222>2,3, 4,5, 6, 7, 8, 9,10,12 , 13, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400&gt; 730 caggcgaggu caucacaagt t 21 &lt;210> 731 &lt;211> 21 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 &gt; 223 &gt; Description of artificial sequence: sRNA suffix stock &lt; 220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-luciferate group" &lt;220> &lt;221>modified_ba.se &lt;222 〉1, 2,8,10, 13,14,17, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified-base-389-152219·sequence table.doc 201130494 &lt;222 〉3,4,5, 6,7,9, 11,12, 15,16,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 731 ucgaggauau gacugauaut t 21 &lt;210&gt; 732 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; Base &lt;222> 1 &lt;223>/modified base == "nuclear Glycoside: lack of 5'-caprate group" &lt;220> &lt;221&gt; modified_base &lt;222>2,5,9,11 &lt;223>/modified base = "2'-0-methyl Corresponding nucleotides &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'. phosphorothioate thymidine" &lt;220&gt;221&gt; modified_base &lt;;222>1,3,4, 6, 7, 8,10,12,13,14,15,16, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt ; 732 auaucaguca uauccucgat t 21 &lt;210> 733 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; 390· 152219 - Sequence Listing.doc 201130494 &lt;223> Description of artificial sequence: dsRNA Right stock &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221&gt; Modified_bas^ &lt;222>3, 6,7, 8,9, 11,12, 13,15, 17, 18,19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleoside Acid &lt;220〉 &lt;221&gt; modified_base

&lt;222> 21 &lt;223&gt;/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 2, 4, 5, 10, 14 , 16 &lt; 223 > / modified base = "2' · hydroxyl corresponding nucleotide" &lt; 400 > 733 gaugaccucg ccuguauuut t 21 &lt; 210 &gt; 734 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: Lack of 5'-decanoate group" &lt;220> &lt;221>modified_ba.se &lt;222>4,6,16 &lt;223>/modified base = "2'-0-methyl corresponding nucleoside Acid &lt;220&gt; -391 - 152219 · Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-deuterated phosphate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>1, 2, 3,5,7, 8, 9,10, 11, 12,13, 14, &lt;223>/modified base = "2'-hydroxy corresponding Nucleotide &lt;400> 734 aaauacaggc gaggucauct t 21 &lt;210> 735 &lt;211&gt; 21 &lt;;212>DNA&lt;213>Artificialsequence&lt;220>&lt;223> Description of artificial sequence: Sensed strand of dsRNA&lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base Base = "nucleotide: lack of 5'-filler group" &lt;220> &lt;221&gt; modified_base &lt;222>5,9, 11, 13,14,15, 17, 18,19 &lt;223> / Modified base == "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'-thio Phosphate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2,3,4, 6, 7, 8,10,12,16 &lt;223>/modified base = " 2'·hydroxyl corresponding nucleotides &lt;400> 735 agaguaaaca cguuuauuut t 21 •392- 1522丨9·sequence table.doc 201130494 &lt;210&gt; 736 &lt;211> 21 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modifiedbase &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5 '-phosphate group> &lt;220〉

&lt;221〉 modified-base &lt;222&gt; 4, 14 &lt;223&gt;/modified base = "2M3-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,5,6,7,8, 9, 10,11, 12,13, 15, 16,17,18, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 736 aaauaaacgu guuuacucut t 21 &lt;210&gt; 737 &lt; 211 &gt; 211 &gt; 212 &gt; 212 &gt; 213 &gt; 213 &gt; artificial sequence &lt; 220 &gt;&lt; 223 &gt; 223 > Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lacking 55-filler group" -393 - 152219 · Sequence Listing.doc 201130494 &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 2 , 3,4, 5, 6, 7, 9,16, 19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221 Modified_base &lt;222&gt; 8, 10, 11, 12, 13, 14, 15, 17, 18 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 737 ccucucugug aaggauagut t 21 &lt;210> 738 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 10, 12 &lt;223&gt; / Modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'-sulfur Phospho-ester thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2, 4, 5, 6, 7, 8, 9, 11, 13, 14, -394· 152219- Sequence Listing.doc 201130494 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 738 acuauccuuc acagagaggt t 21 &lt;210> 739 &lt;211> 21 &lt;212&gt; DNA &lt;;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: dsRNA Sense shares

&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222>2,5, 7, 8, 9, 11, 12, 15, 18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222 〉 21 &lt;223〉/modified base = "55 · phosphorothioate thymidine" &lt;221〉 modified_base &lt;222>1,3, 4,6, 10, 13, 14, 16, 17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 739 augauguuua uugacaacat t 21 &lt;210> 740 &lt;211> 21 &lt;212> DNA &lt;213&gt;&lt;220>&lt;223> Description of artificial sequence: antisense stock of dsRNA -395 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base Base = "nucleotide: lack of 5' phosphate group" &lt;220 &lt;221> modified_base &lt;222>7,10, 14, 17 &lt;223>/modified base = "2'-0- Methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222& 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2,3,4,5, 6, 8 , 9, 11, 12, 13, 15, &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 740 uguugucaBU aaaca.uca.ut t 21 &lt;210&gt; 741 &lt;211&gt; 21 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA&lt;220&gt;221&gt; modified_base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>4, 7, 8, 9, 10, 13, 14, 17, 18, 19 &lt;223&gt;/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base •396- 152219·sequence table.doc 201130494 &lt;222> 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 2, 3, 5, 6, 11, 12, 15, 16 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 741 agacaacuuu ggccgacuut t 21

&lt;210&gt; 742 &lt;211&gt;21 &lt;212&gt;212&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of V-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 9 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;;220>&lt;221&gt; modified_base &lt;222>1, 2,3, 4, 5,6, 7,8, 10,11, 12, 13, &lt;223>/modified base = "2'- Hydroxy corresponding nucleotide" &lt;400&gt; 742 aagucggcca aaguugucut t 21 &lt;210&gt; 743 - 397- 152219 · Sequence Listing.doc 201130494 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: lack of 5'-phosphate Base &lt;220〉 &lt;221&gt; modified_b a*se

&lt;222>1, 2, 3, 5, 8, 13, 15, 17, &lt;223>/modified base == "2'-0-thiol corresponding nucleotide" &lt;220〉 &lt;;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>4,6, 7, 9 ,10, 11, 12, 14,18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 743 uccauaacag aauacccgat t 21

&lt;210&gt; 744 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> •398- 152219-sequence table.doc 201130494 &lt;221> modified-base &lt;222 〉 6, 14 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified Base = "5'-thiophosphate thymidine" &lt;220> &lt;221> modified-base &lt;222>1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12 , 13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400> 744 ucggguauuc uguuauggat t 21 &lt;210&gt; 745 &lt;211> 21 &lt;212> DMA &lt; 213 &gt; 213 > artificial sequence &lt; 220 &gt;&lt; 223 &gt; 223 > Description of artificial sequence: sRNA suffix stock &lt; 220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'·filling acid group" &lt;220> &lt;221> modified-base &lt ;222>2, 4, 7, 8,10,13,16,18 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223&gt;/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modifiedbase &lt;222>1,3,5,6,9,11 ,12,14, 15,17,19 &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" -399- 152219 - Sequence Listing.doc 201130494 &lt;400> 745 guacaaccgc aguaauacgt t 21 &lt ;210&gt; 746 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222 〉 1 &lt;223〉/modified base == “nuclear Acid: Lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>3,6,17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1 , 2, 4, 5,7,8,9, 10,11, 12, 13,14, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 746 cguauuacug cgguuguact t 21 &lt;210> 747 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA • 400· 152219 - Sequence Listing. 201130494 &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-steanate group" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>1, 4, 5,8, 10,12,14,16, 18,19 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-thiolate Thymidine ester "

&lt;221〉 modified-base &lt;222>2, 3, 6,7,9, 11,13, 15, 17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 747 ugauuagcac acaugcgcct t 21 &lt;210&gt; 748 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt;

&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 55· "Actraate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; δ, 14, 18 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220〉 &lt;221〉 modified-base &lt;222> 21 -401 _ 152219·SEQ ID NO. doc 201130494 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221 〉 modified_base &lt;222>1,2, 3,4, 6,7, 8,9,10, 11, 12,13, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 748 ggcgcaugug ugcuaaucat t 21 &lt;210&gt; 749 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222> 2,5,6, 9, 11,13, 15,17, 19 &lt;223>/ Modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base == "5'·phosphorothioate Thymidine" &lt;220&gt;221&gt; modified_base &lt;222>1, 3,4, 7,8,10,12, 14,16,18 &lt;223>/modified base = "2'·hydroxyl Corresponding nucleotides &lt;400> 749 augauuagca cacaugcgct t 21 &lt;210> 750 &lt;211> 21 402 152219 · Sequence Listing.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223 〉 Description of artificial sequence: antisense strand of dsRNA &lt;220〉 &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 55-phosphate group" &lt;220 〉 &lt;221〉 modified base &lt;222>4,13,17

&lt;223&gt;/modified base = "2'-0. methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 21 &lt;223&gt;/modified base = "5' - phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2, 3,5, 6,7,8, 9,10,11,12, 14, &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 750 gcgcaugugu gcuaaucaut t 21 &lt;210> 751 &lt;211> 21 &lt;212&gt; DNA <213> Artificial sequence &lt;220&gt;&lt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;;220&gt;&lt;221> modified-base 403 - 152219-sequence table.doc 201130494 &lt;222>2,3,4,5, 7, 8,9,10,12, 14,15, 16 &lt;223> / Modified base = "2, 0·methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "55-thiophosphoric acid &lt;220> &lt;221> modified_base &lt;222>1,6, 11, 13, 17, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 751 gcuuuacuuu auaccugaat ΐ 21 &lt;210&gt; 752 &lt;211> 21 &lt;212> DNA &lt;213&gt; Sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5 '-Phosphate group> &lt;220> &lt;221&gt; modified_base &lt;222>3,7,9,14 &lt;223>/modified base = "2^0-methyl corresponding nucleotide" &lt; 220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "55 · phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2 , 4,5,6, 8,10,11,12, 13, 15, 16, &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" • 404· 152219-sequence table.doc 201130494 &lt;400> 752 uucagguaua aaguaaagct t 21 &lt;210&gt; 753 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA ;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,3,5,8,9 , 10, 12, 17 &lt; 223 > / modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222&gt; 21 &lt;223>/modified Base = "5'-thiophosphate thymidine" &lt;220&gt;&lt;221> modified-base φ &lt;222>2, 4, 6, 7, 11, 13, 14, 15, 16, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 753 ugcaugauuu auagaguaat t 21 &lt;210&gt; 754 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; -405 - 152219 - Sequence Listing.doc 201130494 &lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; Base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>2, 7, 9, 14,18 &lt;223>/modified base = "2 '·0-methyl corresponding nucleotides> &lt;220&gt;&lt;221&gt; modifieci_base &lt;222&gt 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3, 4, 5, 6, 8, 10, 11, 12, 13,15,16, 17, 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 754 uuacucuaua aaucaugcat ΐ 21 &lt;210&gt; 755 &lt;211 〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5: · phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3, 4,7, 8,11, 12, 13, 14 , 16, 17,19 &lt;223>/modified base = "2'-0. thiol corresponding nucleotide" &lt;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/ Modified base = "55-phosphorothioate thymidine" • 406·

152219· Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;222>5,6, 9, 10,15,18 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide &lt;400> 755 cuuuggccga cuucacugut t 21 &lt;210&gt; 756 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence • &lt;220> <223> Description of artificial sequence: antisense stock of dsRNA ;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222 〉 2, 15 &lt;223〉/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt;

&lt;221〉 modified_base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221>modified_ba.se &lt;222>1, 3, 4,5,6, 7, 8, 9, 10, 11, 12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 756 acagugaagu cggccaaagt t 21

&lt;210&gt; 757 &lt;211> 21 &lt;212> DNA • 407- 152219 · Sequence Listing. doc 201130494 &lt; 213 > Artificial Sequence &lt; 220 &gt;&lt; 223 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA ;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2 , 3,4, 6,7,8,14, 16, 17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,5,9, 10,11, 12 , 13, 15, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 757 auccaccuga aaauauugat t 21 &lt;210&gt; 758 &lt;211> 21 &lt;212 〉 DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "Nucleotide: Lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2,5,11 -408·

152219·Sequence List.doc 201130494 &lt;223>/modified base = "2'·0·methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223> / Modified base = "5^ phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 3,4, 6, 7, 8,9, 10, 12, 13,14 , 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 758 ucaauauuuu cagguggaut t 21

&lt;210> 759 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;221&gt; modified_base &lt;222>1,3, 6, 8, 9, 10, 12,13, 14, 15,16, &lt;223>/modified base = "2'-0-methyl corresponding Nucleotide &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'·depletion phosphate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>2,4, 5, 7,11,17 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 759 -409- 152219 - Sequence Listing.doc 201130494 Uguaauguuc acucucacut t 21 &lt;210> 760 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221 〉 modified—base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>13,16,18 &lt;223>/modified base = "2'_0·decyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'· Phosphorothioate thymidine" &lt;220〉 &lt;221&gt; modified_base &lt;222 1, 2, 3, 4, 5,6, 7, 8, 9,10, 11,12, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 760 agugagagug Aacauuacat t 21 &lt;210&gt; 761 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; Modified_base 410· 152219-Sequence table.doc 201130494 &lt;222> 1 &lt;223>/modified base == "nucleotide: lack of phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222 〉1, 3,4, 5, 11,13, 14, 17 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221> modified_base &lt; 222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221>modified-base &lt;222>2,6, 7, 8,9,10 , 12, 15, 16, 18, 19 &lt; 223 > / modified base = "2 ^ hydroxyl corresponding nucleotide" &lt; 400 &gt; 761 caccugaaaa uauugaugat t 21 &lt; 210 &gt; 762 &lt; 211 &gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' phosphoric acid Ester group &lt;220> &lt;221> modified-base &lt;222>2,5,8,14 &lt;223>/modified base = "2'·0-methyl corresponding nucleotide" &lt; 220> &lt;221&gt; modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" -411 - 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;;221&gt; modified_base &lt;222>1,3,4,6,7,9, 10,11, 12, 13, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 762 ucaucaauau uuucaggugt t 21 &lt;210> 763 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group &lt;220> &lt;221&gt; modified_base &lt;222>3, 4 ,5,6,8, 9, 11,13, 16, 17,19 &lt;223>/ Base = "2'-0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate Thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1,2, 7,10, 12, 14, 15,18 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide &lt;400> 763 gacuucacug uacaaccgct t 21 &lt;210&gt; 764 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence 412-152219·sequence table.doc 201130494 &lt;220&gt;&lt;223&gt; Description: Antisense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-dissolvate group" &lt; 220> &lt;221> modified-base &lt;222> 8, 10 &lt;223>/modified base = "2'-0. methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified_base &lt;222>1,2,3,4, 5, 6,7 , 9, 11,12,13, 14,15, 16, 17,18,19 &lt;223>/modified base = '2' hydroxy-corresponding nucleotide "&lt; 400> 764 gcgguuguac agugaaguct t 21

&lt;210> 765 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'·stearate group" &lt;220&gt;&lt;221&gt;&lt;221> modified-base &lt;222>1, 4, 9, 11,12,13,18,19 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" -413- 152219-sequence table.doc 201130494 &lt;220> &lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 3,5,6, 7,8, 10, 14, 15, 16, 17 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 765 uaacagaaua cccgaggcut t 21 &lt;210> 766 &lt;211 〉 21 &lt;212> DNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &l t;221&gt; modified_base &lt;222> 10, 18 &lt;223>/modified base = "2'·0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified_base &lt;222> 21 &lt;;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,4, 5, 6, 7, 8, 9 , 11,12,13, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 766 agccucgggu auucuguuat t 21 • 414· 152219-sequence table.doc 201130494 &lt;210〉 767 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 > Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221> modified-base &lt; 222 &gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;220〉 &lt;221> modified-base &lt;222>3,11,12, 15,16,18 &lt;223>/modified base = "25-0-fluorenyl corresponding nucleotide" &lt; 220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1, 2,4, 5, 6, 7, 8,9,10,13,14,17, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400&gt; 767 aguaagagga cuggcugugt t 21 &lt;210> 768 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221&gt; modified_base &lt;222> 1 • 415- 152219 - Sequence Listing.doc 201130494 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1, 3,7, 16 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; raodified_base &lt; 222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>2, 4,5,6,8,9 , 10,11,12, 13, 14, 15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 768 cacagccagu ccucuuacut t 21 &lt;210> 769 &lt;211 〉 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/ Modified base = "nucleotide: missing 5 -phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 4,6, 9, 12, 14, 19 &lt;223>/modified base = "2'-0-methyl corresponding Nucleotide &lt;220&gt;&lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base == "5'-phosphorothioate thymidine" &lt;220&gt; -416-1522丨9-Sequence List.doc 201130494 &lt;221&gt; modified_base &lt;222>1,2,5,7,8,10,11,13,15, 16,17, &lt;223>/modified base = " 2'·hydroxyl corresponding nucleotide” &lt;400> 769 aaccgcagua auacggaaut t 21 &lt;210&gt; 770 &lt;211&gt; 21 &lt;212> DNA &lt;213>artificial sequence &lt;220> ^ &lt;223> artificial sequence Description: Antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5'-can acid ester group" &lt;220&gt;&lt;221〉 modified-base &lt;222> 7, 10 &lt;223>/modified base = "2'-0·methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt; 222> 21 W &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;22 0〉 &lt;221&gt; modified_base &lt;222>1, 2, 3,4, 5, 6,8,9,11,12, 13, .14, &lt;223>/modified base = "2'- Hydroxy corresponding nucleotide" &lt;400> 770 auuccguauu acugcgguut t 21 &lt;210&gt; 771 &lt;211> 21 &lt;212> DNA &lt; 213> artificial sequence 417 - 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221&gt; modified_base &lt;222>1, 3,4,5,7,8, 9,10, ]1,]2,13, 14, &lt;223>/modified base = " 2'-0-thiol corresponding nucleotide" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220 〉 &lt;221&gt; modified_base &lt;222>2,6,]6, 18,19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 771 ugucuacccu cuccuguaat t 21 &lt ;210> 772 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 4,14,18 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" -418· 152219 - Sequence Listing .doc 201130494 &lt;220&gt;&lt;221〉 modified-base &lt;222&gt; 21 &lt;223>/modified base = "55-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt; 222>1,3,5,6,7,8,9, 10,11, 12, 13,15, &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 772 uuacaggaga ggguagacat t 21

&lt;210&gt; 773 &lt;211> 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base I &lt;222>3, 6, 7, 8, 9, 12, 13, 16, 17, 18, 19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223&gt;/modified base = "5'-phosphorothioate thymidine" &lt;220&gt;&lt;221> modified_base &lt;222>1,2,4, 5, 10,11, 14, 15 &lt ;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 773 gacaacuuug gccgacuuct t 21 •419- 152219·sequence table.doc 201130494 &lt;210> 774 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; == "Nucleotide: Missing 5'·Actraate Group" &lt;220&gt ; &lt;221&gt; modified_base &lt;222> 10 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221&gt; modified_base &lt;222> 21 &lt; 223>/modified base = "5'. phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 3, 4, 5, 6, 7, 8, 9, 11,12, 13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 774 gaagucggcc aaaguuguct t 21 &lt;210> 775 &lt;211> 21 &lt;212&gt ; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-decarboxylate group" -420· 152219-sequence table.doc 201130494 &lt;220> &lt;221> modified_base &lt;222>4,6, 7,8, 13, 14, 16 , 18 &lt; 223 > / modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222&gt; 21 &lt;223>/modified base = "5'·Thionothioate thymidine" &lt;220〉 &lt;221〉 modified-base &lt;222〉 1, 2, 3,5,9,10, 11, 12, 15,17, 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide"

&lt;400> 775 gaauacccga ggcugcaugt t 21 &lt;210&gt; 776 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: antisense strand of dsRNA &lt; 220>

&lt;221〉 modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1,5,15 &lt;223>/modified base = "2'-0-methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/ Modified base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221>modified-ba.se -421 - 152219 - Sequence Listing.doc 201130494 &lt;222>2, 3, 4, 6, 7,8,9, 10,11,12,13, 14, &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 776 caugcagccu cggguauuct t 21 &lt;210> 777 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt; 223>/modified base = "nucleotide: lack of 5' phthalate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>2, 3,4, 6,8,9, 14, 15 , 19 &lt;223>/modified base == "2'·0-methyl corresponding nucleotide" &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,5, 7, 10, 11, 12,13, 16,17,18 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 777 acuuacauca aaguuaggut t 21 &lt;210> 778 &lt;211> 21 &lt ;212>DNA&lt;213>Artificial sequence&lt;220&gt; 422-152219-Sequence table.doc 201130494 &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 4, 15 &lt;223>/modified base = "2'-0-thiol corresponding nucleotide" &lt;220〉 &lt;221〉 modified base

&lt;223>/modified base == "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1,2,3,5,6,7,8,9 ,10, 11,12, 13, &lt;223>/modified base = "2^hydroxy corresponding nucleotide" &lt;400&gt; 778

Accuaacuuu gauguaagut t 21 &lt;210> 779 &lt;211> 21 &lt;212&gt; DNA ^ &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt; 221〉 modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3, 4, 7,9,11,13, 15, 17, 18,19 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220&gt; -423 · 152219 - Sequence Listing. Doc 201130494 &lt;221&gt; modified_base &lt;222> 21 &lt;223>/modified base = "5'-phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt;222>1, 2, 5, 6, 8, 10, 12, 14, 16 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 779 gauuagcaca caugcgccut t 21 &lt;210> 780 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; / Modified base = "nucleotide: lack of V -phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>6,15 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt;220> &lt; 221〉 modified_base &lt;222&gt; 21 &lt;223>/modified base = "5'·phosphorothioate thymidine" &lt;220> &lt;221> modified-base &lt;222>1,2,3, 4, 5,7, 8, 9,10, 11,12,13, &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 780 aggcgcaugu gugcuaauct t 21 • 424 · 152219 · Sequence Listing.doc 201130494 &lt;210> 781 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221〉 modified-base &lt;222>1,2,4,6,7,12,13,17 &lt;223>/modified base = "2'-0-fluorenyl corresponding nucleotide" &lt ;220&gt;&lt;221> modified-base &lt;222> 21 &lt;223>/modified base = "5:-phosphorothioate thymidine" &lt;220&gt;&lt;221&gt; modified_base &lt;222>3 ,5, 8,9,10, 11, 14, 15, 16,18, 19 &lt;223>/modified base == "2^hydroxy corresponding nucleotide" &lt;400&gt; 781 uuacaucaaa guuagguggt t 21 &lt ;210&gt; 782 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221> modified_base &lt;222 〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate group" -425 - 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222>2, 6,17 &lt;223>/modified base = "2'-0.methyl corresponding nucleotide" &lt;220> &lt;221> modified-base &lt;222> 21 &lt;223>/modified base Base = "5'. Phosphorothioate thymidine" &lt;220> &lt;221&gt; modified_base &lt; 222>1, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 18, 19 &lt;223>/modified base = "2'-hydroxy corresponding core "Glycosylation" &lt;400&gt; 782 ccaccuaacu uugauguaat t 21 &lt;210> 783 &lt;211&gt; 1145 &lt;212> DNA &lt;213> Homo sapiens &lt;220&gt;&lt;223> cDNA of human IL-18 &lt;300&gt;; &lt; 308> NM an 001562. 2 &lt; 309> 2009-12-13 &lt; 400 &gt; 783 attctctccccagcttgctgagccctttgctcccctggcgactgcctggacagtcagcaa 60 ggaattgtctcccagtgcattttgccctcctggctgccaactctggctgctaaagcggct 120 gccacctgctgcagtctacacagcttcgggaagaggaaaggaacctcagaccttccagat 180 cgcttccictcgcaacaaactatttgtcgcaggaataaagatggctgctgaaccagtaga 240 agacaattgcatcaactttgtggcaatgaaatttattgacaatacgctttactttatagc 300 tgaagatgatgaaaacctggaatcagattactttggcaagcttgaatctaaattatcagt 360 cataagaaatttgaatgaccaagttctcttcattgaccaaggaaatcggcctctatttga 420 agatatgactgattctgactgtagagataatgcaccccggaccatatttattataagtat 480 gtataaagatagccagcctagaggtatggctgtaactatctctgtgaagtgtgagaaaat 540 ttceiactctctcctgtgagaacaaaattatttcctttaaggaaatgaatcctcctgataa 600 c Atcaaggatacaaaaagtgacatcatattcittcagagaagtgtcccaggacatgataa 660 taagatgcaatttgeiatcttcatcatacgaaggatactttctagcttgtgaaaaagagag 720 agacctttttaaactcattttgaaaaaagaggatgeiattgggggatagatctataatgtt 780 -426-

152,219 * Sequence Listing .doc 201130494 cactgttcaaaacgaagactagctattaaaatttcatgccgggcgcagtggctcacgcct 840 gtaatcccagccctttgggaggctgaggcgggcagatcaccagaggtcaggtgttcaaga 900 ccagcctgaccaacatggtgaaacctcatctctactaaaaatacaaaaaattagctgagt 960 gtagtgacgcatgccctcaatcccagctactcaagaggctgaggcaggagaatcacttgc 1020 actccggaggtagaggttgtggtgagccgagattgcaccattgcgctctagcctgggcaa 1080 caacagcaaaactccatctcaaaaaataaaataaataaataaacaaataaaaaattcata 1140 atgtg 1145 &lt; 210> 784 &lt; 211> 1165 &lt; 212> DNA &lt; 213> cynomolgus

&lt;220&gt;&lt;223> cDNA of cynomolgus IL-18 &lt;220> &lt;221> modified_base &lt;222&gt; 204, 205, 206, 207, 208, 209, 223, 855, 956, 977, 978 , 987, 1070, 1124, 1125, 1126, 1127, 1128, 1129, 1141, 1142, 1143, 1144, 1145, 1146, 1158, 1159, 1160, 1161, 1162, 1163, 216, 1118, 1135, 1152, 210, 211, 212, 213, 214, 215, 1113, 1114, 1115, 1116, 1117, 1130, 1131, 1132, 1133, 1134, 1147, 1148, 1149, 1150, 1151, 1164, 1165 217, 218, 219, 220,221, 222, 1119,1120,1121,1122, 1123, 1136,1137,1138,1139,1140, 1153, 1154, 1155,1156,1157, &lt;223>/modified base = "unknown nucleoside Acid" &lt;400&gt; 784

attctctcccgagcctgctgagccctttgctcccctggcgactgcctggacaggcagcaa 60 ggagttgtctcccagtgcgttttgccctcctagctgccaactctggctgctaaagcggct 120 gccacctgctacagtctgttacacagcctcgggaagaggaaagggacctcggaccttcca 180 gattgctttctctagcaagaaacnnnnnnnnnnnnnnnnnnnnatggctgctgaaccagc 240 agaagacaattgcatcaattttgtggcaatgaaatttattgacagtacgctttactttat 300 agctgaagatgatgaaaacctggaatcagattactttggcaagcttgaatctaaattatc 360 aatcataagaaatttgaatgacceiagttctcttcattgaccaaggaaatcggcccctatt 420 tgaagatatgactgattctgactgtagagataatgcaccccggaccat-atttattataaa 480 tatgtataaagatagccagcctagaggtatggctgtagccatctctgtgaaatgtgagaa 540 aatttcaactctctcctgtgagaacagaattatttcctttaaggaaat-gaatcctcctga 600 taacatcaaggatacgaaaagtgacatcatattctttcagagaagtgtcccaggacatga 660 taataagatgcaatttga.atcttcatcatacgaa.ggatactttctagcttgtgaaaaa.ga 720 gagagacctttataaactcattttgaaaaaaaaggatgaattgggggatagatctataat 780 gtt, cactgttcaaaa.cga.agactagctattaaaatttcatgcygggcrcrgtggctcamg 840 cctgtaatcccagcnactttgggaggcygagrygggygsrkmwcmygagkkswsrrgagt 900 tcaagaccwgcctgrcc aacatrrtgaaaccysgtctctaytaaaaatacaaaaajittag 960 ctgggcgtggtggtggnntcgcctatnaatcccagcta.ctt, gggaggctgaggcagraga 1020 427- 152219- Sequence Listing .doc 201130494 atyacattrmrctccgagaggcagaggttgtggtgagccgagatcatgcncactgcactc 1080 cagcctgggyracarcagcragactyyrtctynnnnnnnnnnnnnnnnnnnnnnnnnnnn 1140 nnnnnnnnnnnnnnnnnnnnnnnnn 1165 &lt; 210 &gt; 785 &lt; 211> 865 &lt; 212 &gt; DNA &lt; 213> Mus musculus &lt; 220> &lt; 223> cDNA of mouse IL-18 of &lt; 300> &lt; 308> NM a 008360 · 1 &lt; 309> 2009-12-13 &lt; 400 &gt; 785 ggcacagctggacctggtgggggttctctgtggttccatgctttctggactcctgcctgc 60 tggctggagctgctgacaggcctgacatcttctgcaacctccagcatcaggacaaagaaa 120 gccgcctcaaaccttcceiaatcacttcctcttggcccaggaacaatggctgccatgtcag 180 aagactcttgcgtcaacttcaaggaaatgatgtttattgacaacacgctttactttatac 240 ctgaagaaaatggagacctggaatcagacaactttggccgacttcactgtacaaccgcag 300 taatacggaatataaatgaccaagttctcttcgttgacaaaagacagcctgtgttcgagg 360 atatgactgatattgatcaaagtgccagtgaaccccagaccagactgataatatacatgt 420 acaaagacagtgaagtaagaggactggctgtgaccctctctgtg aaggatagtaaaatgt 480 ctaccctctcctgtaagaacaagatcatttcctttgaggaaatggatccacctgaaaata 540 ttgatgatatacaaagtgatctcatattctttcagaaacgtgttccaggacacaacaaga 600 tggagtttgaatcttcactgtatgaaggacactttcttgcttgccaeLaaggaagatgatg 660 ctttcaaactcattctgaaaaaaaaggatgaaaatggggataaatctgtaatgttcactc 720 tcactaacttacatcaaagttaggtggggagggtttgtgttccagaaagatgattagcac 780 acatgcgccttgtgatgacctcgcctgtatttccataacagaatacccgaggctgcatga 840 tttatagagtaaacacgtttatttg 865 &lt; 210 &gt; 786 &lt; 211 &gt; 42 &lt; 212> DNA &lt; 213> Artificial Sequence &lt; 220> &lt; 223> Description of Artificial Sequence of: Human IL-18 bDNA probe • 428-

152219-Sequence table.doc 201130494 &lt;400&gt; 786 ccgctttagc agccagagtt gtttttctct tggaaagaaa gt 42 &lt;210&gt; 787 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Artificial sequence Description: Human IL-18 bDNA probe &lt;400&gt; 787 tagactgcag caggtggcag tttttctctt ggaaagaaag t 41

&lt;210&gt; 788 &lt;211> 44 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence··human IL-18 bDNA probe &lt;400> 788 gatctggaag gtctga .ggtt ccttttttct cttggaaaga aagt 44

&lt;210&gt; 789 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 789 aatagtttgt tgcgagagga agctttttct cttggaaaga aagt 44 &lt;210&gt; 790 &lt;211&gt; 46 &lt;212&gt; DNA &lt;213&gt; artificial sequence 429·152219-sequence table.doc 201130494 &lt;220> &lt;223&gt; 223> Description of artificial sequence: human IL-18 bDNA probe &lt;;400&gt; 790 acaggagaga gttgaaattt tctcattttt ctcttggaaa gaaagt 46 &lt;210> 791 &lt;211> 47 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;

&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 791 tccttaaagg aaataatttt, gttctctttt tctctt.ggaa agaaagt 47 &lt;210> 792 &lt;211&gt; 44 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 792 gctgactgtc caggcagtcg tttttaggca taggacccgt gtct 44

&lt;210&gt; 793 &lt;211&gt; 45 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 793 tgcactggga gacaattcct ttttttaggc Ataggacccg tgtct 45 &lt;210> 794 &lt;211&gt; 48 430- 152219 · Sequence Listing.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence &lt;220〉 &lt;223> Description of Artificial Sequence: Human IL-18 bDNA probe &lt;400> 794 caattgtctt ctactggttc agcattttta ggcataggac ccgtgtct 48 &lt;210> 795 &lt;211> 48 &lt;212> DNA &lt;213> artificial sequence

&lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 795 gattccaggt tttcatcatc ttcattttta ggcataggac ccgtgtct 48 &lt;210&gt; 796 &lt;211> 47 <212> DNA &lt;213> Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 796 atcttcaaat agaggccgat ttctttttag gcataggacc cgtgtct 47 &lt;210&gt; 797 &lt;211> 51 &lt;212&gt; DNA &lt;;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 797 cacttcacag agatagttac agccatattt ttaggcatag gacccgtgtc t 51 -431 - 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 798 &lt;211> 49 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 798 cttgatgtta tcaggaggat tcattttttt aggcatagga cccgtgtct 49 &lt;210> 799 &lt;211> 18 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400> 799 gcagccagga gggcaaaa 18 &lt;210〉 800 &lt;211> 20 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 800 ttcctcttcc cgaagctgtg 20 &lt;210> 801 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human IL-18 bDNA probe • 432-

152219-Sequence table.doc 201130494 &lt;400> 801 gccatcttta ttcctgcgac a 21 &lt;210&gt; 802 &lt;211> 23 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Human IL-18 bDNA probe &lt;400&gt; 802 atttcattgc cacaaagttg atg 23

&lt;210> 803 &lt;211> 28 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 803 gctataaagt aaagcgtatt gtcaataa 28

&lt;210> 804 &lt;211> 24 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 804 gattcaagct tgccaaagta atct 24 &lt;210&gt; 805 &lt;211> 29 &lt;212> DNA &lt;213>Artificial sequence 433 - 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence: human IL-18 bDNA Probe &lt;400&gt; 805 cattcaaatt tcttatgact gataattta 29 &lt;210&gt; 806 &lt;211> 24 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human IL-18 &lt;400&gt; 806 cttggtcaat gaagagaact tggt 24 &lt;210> 807 &lt;211> 29 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 807 gcattatctc tacagtcaga atcagtcat 29

&lt;210> 808 &lt;211&gt; 24 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 808 cttataataa atatggtccg gggt 24 &lt;210> 809 &lt;211&gt; 27 434-152219·SEQ ID NO.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Human IL-18 bDNA Probe &lt;400> 809 cctctaggct ggctatcttt atacata 27 &lt;210&gt; 810 &lt;211&gt; 28 &lt;212> DNA &lt;213> Artificial sequence

&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human IL-18 &lt;400> 810 gaaagaatat gatgtcactt tttgtatc 28 &lt;210> 811 &lt;211> 41 &lt;212> DNA &lt;213&gt; Sequence &lt;220〉

&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 811 gaatttgcca tgggtggaat tttttctctt ggaaagaaag t 41 &lt;210> 812 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt ; &lt;223&gt; Description of artificial sequence: bDNA probe for human GAPDH &lt;400> 812 ggagggatct cgctcctgga tttttctctt ggaaagaaag t 41 -435 - 152219 - sequence listing. doe 201130494 &lt;210> 813 &lt;211&gt; 40 &lt;212&gt DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 813 ccccagcctt ctccatggtt ttttctcttg gaaagaaagt 40 &lt;210> 814 &lt;211&gt; 40 &lt;212 〉 DNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: bDNA Probe for Human GAPDH &lt;400&gt; 814 gctcccccct gcaaatgagt ttttctcttg gaaagaaagt 40 &lt;210> 815 &lt;211> 42 &lt;212 〉 DNA &lt;213>Artificial sequence&lt;220> &lt;223> Description of artificial sequence··bDNA probe of human GAPDH&lt;400> 815 agccttgacg gtgccatgtt tttaggcata ggacccgtgt ct 42 &lt;210> 816 &lt;211> 45 &Lt;212>DNA&lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human GAPDH -436-

152219 - Sequence Listing.doc 201130494 &lt;400&gt; 816 gatgacaagc ttcccgttct ctttttaggc ataggacccg tgtct 45 &lt;210> 817 &lt;211&gt; 46 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description: bDNA probe for human GAPDH &lt;400&gt; 817 agatggtgat gggatttcca tttttttagg cataggaccc gtgtct 46

&lt;210&gt; 818 &lt;211&gt; 44 &lt;212&gt; DNA &lt; 213 &gt; artificial sequence &lt;220&gt; <223> Description of artificial sequence: bDNA probe for human GAPDH &lt;400> 818 gcatcgcccc acttgatttt tttttaggca taggacccgt gtct 44 &lt;210> 819 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 819 cacgacgtac tcagcgccat ttttaggcat aggacccgtg tct 43 &lt;210> 820 &lt;211> 46 &lt;212&gt; DNA &lt;213&gt; artificial sequence 437-152219. Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; Ggcagagatg atgacccttt tgtttttagg cataggaccc gtgtct 46 &lt;210> 821 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 821 ggtgaagacg ccagtggact c 21 &lt;210&gt; 822 &lt;211> 38 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: mouse IL_18 bDNA probe &lt;400&gt; 822 ccagccagca ggcaggattt ttctcttgga aagaaagt 38

&lt;210> 823 &lt;211> 39 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400> 823 tgtcaggcct Gtcagcagct tttttgaagt taccgtttt 39 &lt;210> 824 &lt;211> 40 438· 152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;&lt;223> Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 824 gatgctggag gttgcagaag atttttctga gtcaaagcat 40 &lt;210> 825 &lt;211> 41 &lt;212&gt; DNA &lt;213> Mus musculus

&lt;220&gt;&lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 825 gaggcggctt tctttgtcct tttttctctt ggaaagaaag t 41 &lt;210> 826 &lt;211> 45 &lt;212> DNA &lt; 213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: mouse IL-18 bDNA probe

&lt;400> 826 aagaggaagt gatttggaag gttttttttc tcttggaaag aaagt 45 &lt;210&gt; 827 &lt;211> 39 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: mouse IL- 18 bDNA probe &lt;400> 827 agccattgtt cctgggcctt tttctcttgg aaagaaagt 39 •439- 152219-sequence table.doc 201130494 &lt;210&gt; 828 &lt;211&gt; 41 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of mouse IL-18 &lt;400> 828 cgcaagagtc ttctgacatg gctttttgaa gttaccgttt t 41 &lt;210> 829 &lt;211> 45 &lt;212> DNA φ &lt;213〉 Mus musculus &lt;220> &lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 829 aataaacatc atttccttga agttgatttt, tctgagtcaa agcat 45 &lt;210> 830 &lt;211> 45 &lt;212 〉 DNA &lt;213> Mus musculus

&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of mouse IL-18 &lt;400> 830 tcaggtataa agtaaagcgt gttgtctttt tgaagttacc gtttt 45 &lt;210&gt; 831 &lt;211&gt; 42 &lt;212> DNA &lt; 213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: mouse IL-]8 bDNA probe 152219 · Sequence Listing. doc -440- 201130494 &lt;400&gt; 831 ctgattccag gtctccattt tcttttttct gagtcaaagc at 42 &lt 210> 832 &lt;211> 22 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: mouse IL-18 bDNA probe &lt;400> 832 cagtgaagtc ggccaaagtt Gt 22

&lt;210&gt; 833 &lt;211&gt; 43 &lt;212> DNA <213> Mus musculus &lt;220> &lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 833 atattccgta ttactgcggt Tgtatttttg aagttaccgt ttt 43 &lt;210&gt; 834 &lt;211> 43 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 834 tcaacgaaga gaacttggtc attttttttc tgagtcaaag cat 43 &lt;210&gt; 835 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213> Mus musculus • 441 - 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;223>Artificial Description of the sequence: mouse IL-18 bDNA probe &lt;400> 835 ctcgaacaca ggctgtcttt tgtttttctc ttggaaagaa agt 43 &lt;210> 836 &lt;211&gt; 46 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;

&lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 836 ggcactttga tcaatatcag tcatatcttt ttgaagttac cgtttt 46 &lt;210> 837 &lt;211> 41 &lt;212> DNA &lt;213> Mouse &lt;220> &lt;223> Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 837 tcagtctggt ctggggttca cttttttctg agtcaaagca t 41

&lt;210> 838 &lt;211&gt; 31 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 838 cttacttcac Tgtctttgta catgtatatt a 31 &lt;210> 839 &lt;211> 40 • 442· 152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: small Mouse IL-18 bDNA probe &lt;400> 839 gagagggtca cagccagtcc ttttttgaag ttaccgtttt 40 &lt;210&gt; 840 &lt;211> 45 &lt;212> DNA &lt;213> Mus musculus

&lt;220> &lt;223> Description of artificial sequence··bDNA probe of mouse IL-18 &lt;400&gt; 840 gggtagacat tttactatcc ttcacatttt tctgagtcaa agcat 45 &lt;210&gt; 841 &lt;211> 47 &lt;212&gt; DNA &lt 213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: mouse IL-18 bDNA probe &lt;400&gt; 841 ggaaatgatc ttgttcttac aggagatttt tctcttggaa agaaagt 47 &lt;210> 842 &lt;211&gt; 40 &lt ;212>DNA &lt;213> Mus musculus <220> &lt;223> Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 842 cgaggctggc actgcacaat ttttctcttg gaaagaaagt 40 - 443 - 152219 · Sequence Listing.doc 201130494 &lt;210> 843 &lt;211> 41 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 843 cttcaccatt ttgtctacgg gatttttgaa Gttaccgttt t 41 &lt;210> 844 &lt;211> 39 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; Ccaaatccgt tcacaccgac tttttctgag tcaaagcat 39 &lt;210&gt; 845 &lt; 211 &gt; 38 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt; 223> Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400> 845 ccaggcgccc aatacggttt ttctcttgga aagaaagt 38 &lt;210&gt; 846 &lt;211> 38 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223> Description of artificial sequence: bDNA probe of mouse GAPDH • 444·

152219-Sequence table.doc 201130494 &lt;400&gt; 846 caaatggcag ccctggtgat ttttgaagtt accgtttt 38 &lt;210> 847 &lt;211> 41 &lt;212> DNA &lt;213> Mus musculus &lt;220> &lt;223> artificial sequence Description: bDNA probe for mouse GAPDH &lt;400&gt; 847 aacaatctcc actttgccac tgtttttctg agtcaaagca t 41

&lt;210> 848 &lt;211> 19 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400> 848 tgaaggggtc gttgatggc 19 &lt;210&gt; 849 &lt;211> 26 &lt;212> DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 849 catgtagacc atgtagttga ggtcaa 26 &lt;210&gt; 850 &lt;211&gt; 44 &lt;212> DNA &lt;213> Mus musculus -445 · 152219 · Sequence Listing.doc 201130494 &lt;220&gt;&lt;223> Description of artificial sequence: mouse GAPDH bDNA probe &lt;400&gt; 850 ccgtgagtgg agtcatactg gaatttttct cttggaaaga aagt 44 &lt;210> 851 &lt;211> 42 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400> 851 ttgact.gtgc cgttgaattt gtttttctct tggaaagaaa gt 42 &lt;210&gt; 852 &lt;211&gt; 37 &lt;212&gt; DNA &lt;213&gt; Mouse &lt;220> &lt;223> Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 852 agcttcccat tctcggcctt tttgaagtta ccgtttt 37

&lt;210&gt; 853 &lt;211> 38 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 853 gggct.tcccg Ttgat.gacat ttttctgagt caaagcat 38 &lt;210&gt; 854 &lt;211&gt; 41 446- 152219 · Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213> Mus musculus &lt;220> &lt;223> Description of artificial sequence · bDNA probe of mouse GAPDH &lt;400&gt; 854 cgctcctgga agatggtgat tttttctctt ggaaagaaag t 41 &lt;210&gt; 855 &lt;211> 23 &lt;212&gt; DNA &lt;213> Mus musculus

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of mouse GAPDH &lt;400> 855 cccatttgat gttagtgggg tct 23 &lt;210> 856 &lt;211> 41 &lt;212&gt; DNA &lt;213&gt; Description of mouse &lt;220> &lt;223&gt; artificial sequence: bDNA probe of mouse GAPDH &lt;400&gt; 856 atactcagca ccggcctcac tttttctctt ggaaagaaag t 41 &lt;210> 857 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213 〉Artifical sequence &lt;220&gt;&lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 -447- 152219 · Sequence Listing.doc 201130494 &lt;223〉/ Modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxyl Corresponding nucleotides &lt;400&gt; 857 gaaacacuuu gccgcaggct t 21 &lt;210> 858 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: dsRNA Antisense stock &lt;220〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphorus Acid ester group &lt;220> &lt;221> modified_base &lt;222>1·. 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 858 gccugcggca aaguguuuct t 21 &lt;210&gt; 859 &lt;211&gt; 21 &lt;212> DNA &lt; 213 &gt; 213 &gt; artificial sequence &lt;220&gt; <223> Description of artificial sequence: sRNA's sensible stock &lt;220> &lt;221> modified a base &lt ;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" -448- 152219-sequence table.doc 201130494 &lt;220> &lt;221> modified_base &lt;222 〉1·. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 859 gaaauaauuu ggcgcaggct t 21 &lt;210&gt; 860 &lt;211> 21 &lt;212> DNA &lt;;213>Artificial sequence

&lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 55· Phosphate group" &lt;220> &lt;221> modified-base &lt;222>1·· 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 860 gccugcgcca aauuauuuct t 21 &lt;210> 861 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-filler group" • 449-152219-sequence table.doc 201130494 &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 861 cagacuauuu accgcagggt t 21 &lt;210> 862 &lt;211&gt; 21 &lt;212&gt ; DNA &lt;213> artificial sequence

&lt;220> &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1··19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 862 cccugcggua aauagucugt t twenty one

&lt;210> 863 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt; • 450·152219·sequence table.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 1.. 19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 863 gaaacucuuu guggcaggat t 21 &lt;210> 864 &lt;211> 21 &lt;212> DNA &lt ;213>Artificial sequence&lt;220〉

&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220&gt;&lt;221&gt; rnodified_base &lt;222>1· _ 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 864 uccugccaca aagaguuuct t 21 &lt;210 〉 865 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222 〉 1 &lt;223>/modified base = "nucleotide: lack of 5:-filled acid ester group" &lt;220> &lt;221> modified-base 152219-sequence table.doc -451 - 201130494 &lt;222&gt 1.. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 865 gaaacuuuuu gucacaggut t 21 &lt;210> 866 &lt;211> 21 &lt;212> DNA &lt;;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleoside acid Lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; Accugugaca aaaaguuuct t 21 &lt;210&gt; 867 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-filler group" &lt;220&gt;&lt;221> modified_base &lt;222>1·. 19 -452 - 152219 · Sequence Listing.doc 201130494 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 867 aaagcaauuu guugcaggct t 21 &lt;210> 868 &lt;211> 21 &lt;212 〉 DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223> Description of Artificial Sequence: Antisense Unit of dsRNA

&lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222 〉1·· 19 &lt;223>/modified base = "2s-hydroxy corresponding nucleotide" &lt;400&gt; 868 gccugcaaca aauugcuuut t 21 &lt;210> 869 &lt;211> 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide : lack of 5'-decanoate group" &lt;220> &lt;221> modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" -453 - 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 869 uaaagaauuu gucacaggat t 21 &lt;210&gt; 870 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Antisense stock of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; m Odified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 870 uccugugaca aauucuuuat t 21 &lt;210> 871 &lt;211> 21 &lt; 212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide • 454·

152219-Sequence List.doc 201130494 &lt;400> 871 uaaucuacuu guugcaggat t 21 &lt;210> 872 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense stock of dsRNA &lt;220〉 &lt;221〉 modified-base

&lt;223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified Base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 872

Uccugcaaca aguagauuat t 21 &lt;210> 873 &lt;211> 21 &lt;212> DNA U &lt; 213 > artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: sRNA sine stock &lt;220> &lt;221&gt; modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221>modified_ba.se &lt;222> 1 ··19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 873 -455 - 152219 · Sequence Listing.doc 201130494 aaaaccauug guugcaggat t 21 &lt;210> 874 &lt;211 〉 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA&lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1..19 &lt;223>/modified base = "2'-hydroxyl Corresponding nucleotides &lt;400> 874 uccugcaacc aaugguuuut t 21 &lt;210> 875 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: d Sense of sRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> &lt;221> Modified-base &lt;222>1.. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 875 gaaacuaagu guggcagggt t 21 •456·

152219 - Sequence Listing.doc 201130494 &lt;210&gt; 876 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; Artificial Sequence &lt;220&gt; <223> Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;;221&gt; modified^base &lt;222> 1 <223> / Modified base = "nucleotide: lack of acid ester group"

&lt;221> modified-base &lt;222>1·. 19 <223&gt; / modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 876 cccugccaca cuuaguuuct t 21 &lt;210&gt; 877 &lt; 211> 21 <212> DNA &lt;213>Artificial sequence&lt;223> Description of artificial sequence: Sensed strand of dsRNA&lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base <222> 1.19 &lt;223>/modified base = "2'-hydroxy corresponding nucleoside Acid &lt;400&gt; 877 caaaguauuu ggcgcuggct t 21 •457 · 152219 · Sequence Listing.doc 201130494 &lt;210> 878 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220〉 &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_b^se &lt;222&gt; 1 <223&gt; / modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1. · 19 &lt;223>/modified base = "25. hydroxyl corresponding nucleotide" &lt;400&gt; 878 gccagcgcca aauacuuugt t 21 &lt;210&gt; 879 &lt;211&gt; 21 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified Base = "2'-hydroxy corresponding nucleotide" &lt;400> 879 cauacuauuu gacgcagaat t 21 -458· 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 880 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: Lack of 5'-phosphate group" &lt;220&gt;

&lt;221〉 modified_base &lt;222>1. . 19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 880 uucugcguca aauaguaugt t 21 &lt;210&gt; 881 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223&gt; / Modified base == "nucleotide: lack of 5'·filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "25 Hydroxy corresponding nucleotide" &lt;400&gt; 881 uccuaaaaca aauaguuuat t 21 &lt;210&gt; 882 -459 - 152219 - Sequence Listing _doc 201130494 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 55-phosphate group &lt;220〉 &lt;221&gt; modified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 882 uaaacuauuu guuuuag Gat t 21 &lt;210&gt; 883 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223> / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 883 uccuguaaca acuaguuuut t 21 &lt;210> 884 &lt;211> 21 460-

152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222 〉 1 &lt;223>/modified base == "nucleotide: lack of 5^ phosphate group" &lt;220> &lt;221> modified_base &lt;222>1.. 19

&lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 884 aaaacuaguu guuacaggat t 21 &lt;210> 885 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt;&lt;220>&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1.. 19 &lt;223&gt;/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt;

Aaauauaaaa agauagccgt t 21 &lt;210> 886 &lt;211> 21 &lt;212> DNA 461 · 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Reverse of dsRNA Stocks &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5' phosphate group" &lt;220&gt;&lt;221&gt; inodified_ba.se &lt;222>1. · 19 &lt;223>/modified base = "Γ-hydroxy corresponding nucleotide" &lt;400&gt; 886 cggcuaucuu uuuauauuut t 21 &lt;210> 887 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = " Nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 1.·19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt ;400&gt; 887 cuuuuaaiiaa. agauagccat t 21 &lt;210&gt; 888 &lt;211&gt; 21 &lt;212> DNA &lt;213> artificial sequence 462-

152219· Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA &lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = " Nucleotide: lack of 5'-steanate group" &lt;220> &lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleoside acid"

&lt;400> 888 uggcuaucuu uauuaaaagt t 21 &lt;210> 889 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt; 220> &lt;221> modified-base &lt;222&gt; 1 φ &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222 〉1·· 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 889 auauggaaga agauagccat t 21 &lt;210&gt; 890 &lt;211> 21 &lt;212&gt; DNA &lt;;213>Artificial sequence 463 - 152219 - Sequence listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222&gt; 1 &lt;223&gt; / Modified base = "nucleotide: lack of 55-decanoate group" &lt;220&gt;&lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified base = "2 '-Hydroxy corresponding nucleotide&gt;&lt;400&gt; 890 uggcuaucuu cuuccauaut t 21 &lt;210> 891 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220&gt;&lt;223&gt; Description of column: Sensed strand of dsRNA &lt;220> &lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of V-phosphate group" &lt;220 〉 &lt;221〉 modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 891 auauuucuua agauagccct t 21 &lt;210&gt; 892 &lt; 211> 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> 464-

152219-SEQ ID NO. doc 201130494 &lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide : lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1··19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 892 gggcuaucuu aagaaauaut t 21

&lt;210> 893 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &lt; 223 &gt; Description of artificial sequence: sRNA suffix stock &lt;220 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group"

&lt;221&gt; modif ied__base &lt;222>1·. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400> 893 ucauguaaca agauagccat t 21 &lt;210> 894 &lt; 211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: antisense strand of dsRNA -465 - 152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;221&gt; Modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222> 1..19 &lt; 223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 894 uggcuaucuu guuacaugat t 21 &lt;210&gt; 895 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence&lt; 220> &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221> modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphoric acid Ester group &lt;220> &lt;221> modified-base &lt;222>1·. 19 &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400&gt; 895 auauauauua ugauagccut t 21 &lt;210&gt; 896 &lt;211&gt; 21 &lt;212> DNA <213> artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA • 466·

152219-Sequence List.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 896 aggcuaucau aauauauaut t 21

&lt;210&gt; 897 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' phosphate group" &lt;220> <221> modified-base &lt;222>1_· 19 &lt;223>/ Modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 897 guauuuagaa acauagccct t 21 &lt;210&gt; 898 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;;223> Description of artificial sequence: antisense strand of dsRNA &lt;220> -467- 152219-sequence table.doc 201130494 &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleoside Acid: Lack of 5'-decanoate group" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" &lt;400&gt; 898 gggcuauguu ucuaaaua.ct t, 21 &lt;210&gt; 899 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt;&lt;223&gt; Description of artificial sequence: sRNA sensible stock &lt;;220 〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 19 &lt;223&gt;/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 899 auaugcauaa aga.uagacut t 21 &lt;210&gt; 900 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: antisense stock of dsRNA &lt;220> &lt;221&gt; modified_base -468-

152219· Sequence Listing.doc 201130494 &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1.. 19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400&gt; 900 agucuaucuu uaugcauaut t 21

&lt;210> 901 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;&lt;222> 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-decanoate group" &lt;220> &lt;221> modified_base &lt;222>1.. 19 &lt;223&gt; / Modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 901 auauguaaaa agauagcact t 21 &lt;210> 902 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 -469- 152219. Sequence Listing.doc 201130494 &lt;223&gt;/modified base = "nuclear Glycosidic acid: lack of 5'·filler group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt ;400&gt; 902 gugcuaucuu uuuacauaut t 21 &lt;210&gt; 903 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; 223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220 〉 &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>1·· 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 903 uuauguauua agauaaccut t 21 &lt;210> 904 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt; / modified base = "nucleotide: lack of 5 '-Dish ester base> •470·

152219-Sequence List.doc 201130494 &lt;220> &lt;221&gt; modified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 904 agguuaucuu Aauacauaat t 21 &lt;210&gt; 905 &lt;211&gt; 21 &lt;212> DNA &lt;213> artificial sequence ^ &lt;220&gt;&lt;223&gt; Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1.. 19 &lt ;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 905

Guauauauaa ggauggccat t 21 &lt;210&gt; 906 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; 〉 modified_base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-phosphate group" • 471 · 152219 - sequence listing.doc 201130494 &lt;220&gt;&lt;221&gt; modified_base &lt;;222>1.· 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 906 uggccauccu uauacauact t 21 &lt;210&gt; 907 &lt;211> 21 &lt;212〉 DNA &lt;213> artificial sequence

&lt;220〉 &lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221〉 modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' -phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 907 auauguauaa agagagacat t twenty one

&lt;210> 908 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt; 222> 1 &lt;223>/modified base == "nucleotide: lack of 5'-phosphate group" &lt;220&gt; •472-152219-sequence table.doc 201130494 &lt;221> modified-base &lt; 222> l._19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 908 ugucucucuu uauacauaut t 21 &lt;210&gt; 909 &lt;211> 21 &lt;212> DNA &lt ;213>Artificial sequence&lt;220〉

&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group &lt;220> &lt;221> modified_base &lt;222>1.. 19 &lt;223>/modified base = "25·hydroxyl corresponding nucleotide" &lt;400&gt; 909 aggcuauuuu uaaacuuaat t 21 &lt;210〉 910 &lt; 211 &gt; 21 &lt; 212 &gt; DNA &lt; 213 &gt; artificial sequence &lt; 220 &lt; 223 &gt; 223 &gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220> &lt;221> modified base • 473 - 152219 - Sequence Listing.doc 201130494 &lt;222&gt; .. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 910 uuaaguauaa aaauagccut t 21 &lt;210&gt; 911 &lt;211> 21 &lt;212> DNA &lt;213 〉Artifical sequence &lt;220&gt;&lt;223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide Lack of 5s·phosphate group &lt;220> &lt;221> modified_base &lt;222> 1·.19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 911 aggcuaucuc Uauacacaat t 21 &lt;210> 912 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; Inodified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5s-phosphate group &lt; 220> &lt;221> modified-base &lt;222&gt; 1..19 •474- 1522丨9-Sequence List.doc 201130494 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 912 uuguguauag agauagccut t 21 &lt;210> 913 &lt;211> 21 &lt;212&gt ; DNA &lt; 213 > Artificial Sequence &lt; 220 &gt;&lt; 223 > Description of Artificial Sequence: Sensed Shares of dsRNA

&lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 <223> / modified base = "nucleotide: lack of 55-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 19 &lt;223>/modified base = "2'_hydroxy corresponding nucleotide" &lt;400&gt; 913 caaaugacau gauaauaaat t 21 &lt;210> 914 &lt;211> 21 &lt;212> DNA &lt;213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified-base &lt;222> 1 &lt;223&gt;/modified base = "nucleotide : Lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1·· 19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" -475 - 152219-Sequence table.doc 201130494 &lt;400> 914 uuuauuauca ugucauuugt t 21 &lt;210> 915 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Sense strand of dsRNA &lt;220> &lt;221> modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; Mo Dified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 915 ccccagccau gauaauaaat t 21 &lt;210> 916 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt; modified-base &lt;222> 1 &lt;223&gt; Base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'-hydroxy corresponding core Glycosylate" -476-

152219· Sequence Listing.doc 201130494 &lt;400&gt; 916 uuuauuauca uggcuggggt t 21 &lt;210&gt; 917 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Sense of dsRNA &lt;220&gt;&lt;221&gt; modified_base

&lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222&gt; 1.. 19 &lt;223>/modified base Base = "2'. Hydroxyl corresponding nucleotide" &lt;400&gt; 917

Cucaugacag gauaauaagt t 21 &lt;210> 918 &lt;211&gt; 21 &lt;212&gt; DNA ^ &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt;222&gt; 1.. 19 &lt; 223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 918 152219 - Sequence Listing. doc -477- 201130494 cuuauuaucc ugucaugagt t 21 &lt;210&gt; 919 &lt;211&gt; 21 &lt;212&gt ; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "Nucleotide: Lack of 5'-phosphate group" &lt;220&gt;&lt;221&gt; modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400> 919 ucaaggaacu gauaauaagt t 21 &lt;210&gt; 920 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description: Antisense stock of dsRNA &lt;220&gt;&lt;221> modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉 &lt;221> modified-base &lt;222>1·. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 920 cuuauuauca guuccuugat t 21 •478 ·

152219-Sequence List.doc 201130494 &lt;210&gt; 921 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;&lt;221&gt; mod ifi ed-bas e <222> 1 &lt;223>/modified base = "nucleotide: lack of phosphate group"

&lt;220> &lt;221> modified-base &lt;222>1..19 &lt;223>/modified base = "Γ-hydroxy corresponding nucleotide" &lt;400&gt; 921 uacaagacau guuaauaagt t 21 &lt;210&gt ; 922 &lt; 211 &gt; 21 &lt;212 > DNA &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Antisense Unit of dsRNA &lt; 220 &gt; 220 &gt; 221 &gt; modified - base &lt; 222 &gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified Base = "Γ-hydroxy corresponding nucleotide" &lt;400&gt; 922 cuuauuaaca ugucuuguat t 21 -479- 152219 - Sequence Listing.doc 201130494 &lt;210&gt; 923 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213&gt; Artificial sequence <220> <223> Description of artificial sequence: Sensed strand of dsRNA &lt;220> &lt;221&gt; modified_base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5' Phosphate group "220220" modified &lt;220&gt; Uaa Aauaagt t 21 &lt;210> 924 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt; Modified-base &lt;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 924 cuuauuuuaa uguccugggt t 21 •480-

152219· Sequence Listing.doc 201130494 &lt;210&gt; 925 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;&lt;221〉 modified_base &lt;222〉 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220〉

&lt;221&gt; modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400> 925 uccaggacau gguaauagut t 21 &lt;210&gt; 926 &lt;211&gt 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Antisense Unit of dsRNA

&lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified_base &lt; 222>1·. 19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 926 acuauuacca uguccuggat t 21 &lt;210> 927 -481 · 152219 · Sequence table.doc 201130494 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: Sensed strand of dsRNA &lt;220&gt;&lt;221&gt;2&lt;221&gt; 223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221>modi fied_l)ase &lt;222> 1..19 &lt;223>/modified base = "2'-hydroxyl corresponding nucleotide" &lt;400&gt; 927 accaggacau gagaauagat t 21 &lt;210&gt; 928 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>artificial sequence &lt;220&gt;&lt;223&gt; Description of the sequence: antisense strand of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221&Gt; modified_base &lt;222&gt; 1..19 &lt;223>/modified base == "2'-hydroxy corresponding nucleotide" &lt;400> 928 ucuauucuca uguccuggut t 21 &lt;210&gt; 929 &lt;211&gt; 21 •482· 152219·Sequence List.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA&lt;220&gt;221&gt; modified_base &lt;;222> 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1·. 19

&lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 929 accaggacau gauuauagct t 21 &lt;210> 930 &lt;211> 21 &lt;212> DNA &lt;213&gt;&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified-base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: absent 5'··········································· Gcuauaauca uguccuggut t 21

&lt;210> 931 &lt;211> 21 &lt;212> DNA • 483 - 152219 · Sequence Listing. doc 201130494 &lt; 213 > Artificial Sequence &lt; 220 &gt; 223 > Description of Artificial Sequence: Sensed Strand of dsRNA ;220> &lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lacking 55-phosphate group" &lt;220&gt;&lt;221&gt; modifiecl_base &lt;222>1, .19 &lt;223>/modified base = "2'·hydroxy corresponding nucleotide" &lt;400&gt; 931 cccaggacau gaaaaaaaut t 21 &lt;210&gt; 932 &lt;211> 21 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base == "nucleotide: Lack of 5'-decanoate group" &lt;220> &lt;221&gt; iuodified_base &lt;222&gt; 1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 932 auuuuuuuca uguccugggt t 21 &lt;210> 933 &lt;211> 21 &lt;212> DNA &lt;213> artificial sequence 484·

152219-Sequence List.doc 201130494 &lt;220> &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220> &lt;221> modified-base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modified-base &lt;222>1. · 19 &lt;223>/modified base = "2'-hydroxy corresponding core Glycosylate

&lt;400> 933 gccaggacau gaucaugact t 21 &lt;210&gt; 934 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt;223 Description of artificial sequence: antisense strand of dsRNA &lt; 220> &lt;221> modified-base &lt;222&gt; 1 φ &lt;223>/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220> &lt;221> modifiedjbase &lt;222 〉1_ · 19 &lt;223>/modified base = "25-hydroxy corresponding nucleotide" &lt;400> 934 gucaugauca uguccuggct t 21 &lt;210> 935 &lt;211> 21 &lt;212> DNA &lt;213 〉Artificial sequence 485 - 152219 - Sequence table.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: sRNA suffix stock &lt;220&gt;&lt;221&gt; modified_base &lt;222> 1 &lt;223>/ Modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;&lt;221> modified-base &lt;222>1.. 19 &lt;223>/modified base = "2'- Hydroxyl corresponding nucleotide" &lt;400> 935 uccaggacau gauacugaut t 21 &lt;210&gt; 936 &lt;211&gt; 21 &lt;212&gt;&gt;213&gt;213>artificial sequence&lt;220&gt;&lt;223&gt; Description: Antisense stock of dsRNA &lt;220&gt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-phosphate group" &lt;220&gt;;221> modified_base &lt;222>1.. 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 936 aucaguauca uguccuggat t 21 &lt;210&gt; 937 &lt;211&gt; 21 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt; 486-

152219 · Sequence Listing.doc 201130494 &lt;223> Description of Artificial Sequence: Sensed Strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223>/modified base = "nucleotide: Lack of 5'-phosphate group" &lt;220> &lt;221&gt; modified_base &lt;222> 1..19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; Auuauuaaca uguccugggt t 21

&lt;210&gt; 938 &lt;211&gt;21 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;221&lt;221&gt;&lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide: lack of 5'-decanoate group"

&lt;220> &lt;221> modified_base &lt;222>1. · 19 &lt;223>/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 938 cccaggacau guuaauaaut t 21 &lt;210&gt; 939 &lt;211&gt; 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Sensed Strand of dsRNA - 487 · 152219 - Sequence Listing.doc 201130494 &lt;220〉 &lt;;221〉 modified—base &lt;222〉 1 &lt;223〉/modified base = "nucleotide: lack of 5'-dissolvate group" &lt;220&gt;&lt;221> modified-base &lt;222> 1. 19 &lt;223&gt;/modified base = "2'-hydroxy corresponding nucleotide" &lt;400&gt; 939 cuuguuguca uguccuggut t 21 &lt;210> 940 &lt;211&gt; 21 &lt;212&gt; DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: antisense strand of dsRNA &lt;220&gt;&lt;221&gt; modified_base &lt;222&gt; 1 &lt;223&gt;/modified base = "nucleotide : lack of 55-phosphate group" &lt;220&gt;&lt;221> modified_base &lt;222>1_ · 19 &lt;223>/modified base = "2'·hydroxyl corresponding nucleotide" &lt;400&gt; 940 accaggacau Galacaacagt t 21 &lt;210&gt; 941 &lt;211&gt; 18 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of human GTPBP2 -488 -

152219 - Sequence Listing.doc 201130494 &lt;400&gt; 941 gcgcagtcgg ggcagtat 18 &lt;210> 942 &lt;211&gt; 20 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human bDNA probe of GTPBP2 &lt;400> 942 ccacgatgaa gaagggcact 20

&lt;210&gt; 943 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence··BDNA probe of human GTPBP2 &lt;400> 943 gggtcaggac tccaagcaga tttttctctt ggaaagaaag t 41 &lt;210&gt; 944 &lt;211> 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400> 944 cccattgtcc agctctccct tttttctctt Ggaaagaaag t 41 &lt;210> 945 &lt;211> 41 &lt;212&gt; DNA &lt;213&gt; artificial sequence 489·152219-sequence table.doc 201130494 &lt;220> &lt;223&gt; 223> Description of artificial sequence: bDNA of human GTPBP2 Probe &lt;400&gt; 945 gccaggtcga tgaaggtgat tttttctctt ggaaagaaag t 41 &lt;210&gt; 946 &lt;211&gt; 40 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &gt; 223 &gt; 223 > Description of Artificial Sequence: Human GTPBP2 bDNA probe

&lt;400> 946 ggcactgacg aggagcaggt ttttctcttg gaaagaaagt 40 &lt;210&gt; 947 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 947 gtgccagcaa tcccagtgtt tttttctctt ggaaagaaag t 41

&lt;210> 948 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 948 gcacataggt cgatcttgct gatttttctc ttggaaagaa agt 43 &lt;210> 949 -490- 152219 · Sequence Listing.doc 201130494 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA Exploration of Human GTPBP2 Needle &lt;400&gt; 949 agccaggctg cttgaggact ttttctcttg gaaagaaagt 40

&lt;210> 950 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 950 tgctgggcag cagtgacgtt tttctcttgg aaagaaagt 39 &lt;210&gt; 951 &lt;211&gt; 36 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 951 ccccaggacg gccacacttt ttgaagttac cgtttt 36 &lt;210&gt; 952 &lt;211&gt;42 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400> 952 gttgacttcc cagagtccac atttttttct gagtcaaagc at 42-491 - 152219-Sequence table.doc 201130494 &lt;210> 953 &lt;211> 33 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 Needle &lt;400> 953 cgagcccggc cccgtttttg aagttaccgt ttt 33 &lt;210&gt; 954 &lt;211> 38 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: bDNA Probe of Human GTPBP2 Needle &lt;400> 954 gtggcggaaa Aggttgagct ttttctgagt caaagcat 38 &lt;210&gt; 955 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400> 955 ggccagactg Aatctcatgc agtttttgaa gttaccgttt t 41 &lt;210&gt; 956 &lt;211> 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 • 492·

152219-Sequence table.doc 201130494 &lt;400&gt; 956 cgaagctgat gctggaggtt ctttttctga gtcaaagcat 40 &lt;210> 957 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence : bDNA probe for human GTPBP2 &lt;400> 957

Tgctgttaaa gcccaggatc ttttttgaag ttaccgtttt 40 &lt;210&gt; 958 &lt;211> 42 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400> 958 Gctgtaattc accacctctc ccttttttct gagtcaaagc at 42 &lt;210&gt; 959 &lt;211&gt; 41 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 959 tctcttctgc tgtccgtgag tctttttgaa gttaccgttt t 41 &lt;210&gt; 960 &lt;211&gt; 42 &lt;212> DNA &lt;213> artificial sequence 493 · 152219 - Sequence Listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400> 960 catcttggag ctgctctcac agatttttct gagtcaaagc at 42 &lt;210&gt; 961 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 961 gtgtgtaggt acttatggtg gccttttttg aagttaccgt ttt 43 &lt;210&gt; 962 &lt;211&gt; 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: bDNA probe for human GTPBP2 &lt;400&gt; 962 gatgtgaggc caaagatggt gtttttctga gtcaaagcat 40

&lt;210&gt; 963 &lt;211&gt;39 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 963 gccccagatg ttcccttgtg tttttgaagt taccgtttt 39 &lt;210&gt; 964 • 494- 152219 - Sequence Listing.doc 201130494 &lt;211&gt; 35 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; 223> Description of Artificial Sequence: bDNA Probe of Human GTPBP2 &lt;400&gt; 964 ttcagggcca gggccatttt tctgagtcaa agcat 35

&lt;210> 965 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 965 tgtcctctcc actgtggtct tgtttttgaa gttaccgttt t 41 &lt;210> 966 &lt;211&gt; 37 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 966 ccgctccagc tggcgtactt tttctgagtc aaagcat 37 &lt;210> 967 &lt;211> 37 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GTPBP2 &lt;400&gt; 967 gcatggggac cttgtggctt tttgaagtta ccgtttt 37-495 - 152219 - Sequence Listing.doc 201130494 &lt;210> 968 &lt;211> 41 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA Probe of Human GTPBP2 Needle &lt;400&gt; 968 gcatcatcct cagaggtgac catttttctg agtcaaagca t 41 &lt;210> 969 &lt;211> 21 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA of human ALPK1 Probe &lt;400&gt; 969 tgg Tcctcgc tcttgtcctc t 21 &lt;210&gt; 970 &lt;211> 21 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 970 tgcaccagga Ccttgtcact t 21 &lt;210> 971 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> 496-

152219-SEQ ID NO: doc 201130494 &lt;223> Description of artificial sequence: bDNA probe of human ALPK1 &lt;400&gt; 971 acttgcttgc actcttgcag tagtttttct cttggaaaga aagt 44 &lt;210> 972 &lt;211> 41 &lt;212> DNA &lt; 213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ALPK1

&lt;400&gt; 972 ggagtaaagc tctgcagcgc tttttctctt ggaaagaaag t 41 &lt;210> 973 &lt;211> 39 &lt;212> DNA <213> Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: human ALPK1 bDNA probe &lt;400&gt; 973 ttgtcctctg ggcccacgtt tttctcttgg aaagaaagt 39

&lt;210> 974 &lt;211&gt; 37 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 974 gccgcagccg cacagttttt tctcttggaa agaaagt 37

&lt;210> 975 &lt;211&gt; 44 &lt;212&gt; DNA 497-152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human ALPK1 bDNA Probe &lt;;400&gt; 975 acctgcagaa. gttttccaga gacttttt.ct cttggaaaga aagt 44 &lt;210&gt; 976 &lt;211> 38 &lt;212&gt; DNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ALPK1 &lt;400> 976 ccacctgcgg ggcaattttt ttctcttgga aagaaagt 38 &lt;210> 977 &lt;211> 48 &lt;212&gt; DNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ALPK1

&lt;400&gt; 977 actgctcaga atatactctg cttttaattt ttctcttgga aagaaagt 48 &lt;210> 978 &lt;211> 46 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA detection of human ALPK1 Needle &lt;400&gt; 978 ccctctgatc tgtatacaga ccgacttttt ctcttggaaa gaaagt 46 -498- 152219 · Sequence Listing.doc 201130494 &lt;210> 979 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223 〉 Description of artificial sequence: bDNA probe for human ALPK1 &lt;400&gt; 979 tccaacaaga gctgatccag ctttttgaag ttaccgtttt 40

&lt;210&gt; 980 &lt;211&gt; 37 &lt;212&gt; DNA &lt;213&gt; Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400&gt; 980 tccgacacat ctggcgcttt tttctgagtc aaagcat 37 &lt;210&gt; 981 &lt;211> 39 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 981 cagggtcctt aactcgctgg tttttgaagt taccgtttt 39 &lt;210&gt; 982 &lt;211> 40 &lt;212&gt; DNA &lt; 213 &gt; 213 &gt;&lt;220&gt;&lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400&gt; 982 -499- 152219- Sequence Listing.doc 201130494 catttccttt gcctcctgga ttttttctga gtcaaagcat 40 &lt;210> 983 &lt;211> 37 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: Human ALPK1 bDNA Probe &lt;400> 983 aggcacgaag ggccactttt tttgaagtta ccgtttt 37 &lt;210&gt; 984 &lt;211&gt;42 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 984 gcttgttt Gt actgccactt ttctttttct gagtcaaagc at 42 &lt;210&gt; 985 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: human ALPK1 bDNA probe &lt;400&gt; 985 ccaatcacat. ccttcaggtt. tgttttttt.g aagttaccgt t.tt 43 &lt;210&gt; 986 &lt;211&gt; 34 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> 500-

152219· Sequence Listing.doc 201130494 &lt;223> Description of Artificial Sequence: bDNA probe of human ALPK1 &lt;400> 986 tgctgcaacc cggcgttttt ctgagtcaaa gcat 34 &lt;210&gt; 987 &lt;211> 39 &lt;212> DNA &lt;213 〉Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human ALPK1

&lt;400> 987 ccctcaggga cgccagtaac tttttgaagt taccgtttt 39 &lt;210&gt; 988 &lt;211&gt; 37 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 988 cccgagcgag gatggaggtt tttctgagtc aaagcat 37 &lt;210> 989 &lt;211> 42 &lt;212> DNA <213> Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: human ALPK1 bDNA probe &lt;;400&gt; 989

Ggtccaccaa gaacacaata gcctttttga agttaccgtt tt 42 &lt;210&gt; 990 &lt;211> 39 &lt;212> DNA 501 - 152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human bDNA probe of ALPK1 &lt;400> 990 gtcgagccca tacaggaacc tttttctgag tcaaagcat 39 &lt;210> 991 &lt;211&gt; 39 &lt;212&gt; DNA &lt;213&gt;

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ALPK1 &lt;400&gt; 991 acttgtggag acctttggcg tttttgaagt taccgtttt 39 &lt;210&gt; 992 &lt;211> 35 &lt;212> DNA &lt;213> artificial sequence &lt;220〉

&lt;223&gt; Description of artificial sequence: bDNA probe of human ALPK1 &lt;400&gt; 992 ggcgtggctg gctgcatttt tctgagtcaa agcat 35 &lt;210&gt; 993 &lt;211&gt; 37 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ALPK1 &lt;400> 993 ttcgggcttg gcgaataatt tttgaagtta ccgtttt 37 152219-sequence table.doc -502- 201130494 &lt;210> 994 &lt;211&gt; 42 &lt;212&gt;&lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe for human ALPK1 &lt;400> 994 aagttttcct gagttcacgg agatttttct gagtcaaagc at 42

&lt;210> 995 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ALPK1 &lt;400> 995 cgttgctcca ttgttgctta ttagtttttg aagttaccgt ttt 43 &lt;210&gt; 996 &lt;211&gt; 42 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human ALPK1 bDNA probe &lt;400> 996 tcatttctgt acagccaggt acctttttct gagtcaaagc At 42 &lt;210&gt; 997 &lt;211&gt; 31 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; MAN2A1 bDNA probe-503 - &lt;223> Description of artificial sequence 152219 - Sequence table.doc 201130494 &lt;400> 997 tcttttttct agtagtattc gaaatagatt a 31 &lt;210> 998 &lt;211> 25 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: MAN2A1 bDNA probe &lt;;400&gt; 998 gagagaagaa gttatgtggc taagg 25

&lt;210&gt; 999 &lt;211&gt; 47 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 999 tttggctttt tatatcagaa gaaatttttt tctcttggaa agaaagt 47 &lt;210&gt; 1000

&lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1000 tgcttgaaga ggcaatttgc ttttttctct. tggaaagaaa gt 42 &lt;210> 1001 &lt;211&gt; 44 &lt;212&gt; DNA &lt;213&gt; artificial sequence 504-152219. Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1001 gcagagagca gtgtcaaacg atgtttttct cttggaaaga aagt 44 &lt;210&gt; 1002 &lt;211> 43 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1

&lt;400> 1002 tcttgcatga gtcttcgatc catttttctc ttggaaagaa agt 43 &lt;210&gt; 1003 &lt;211> 46 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1003 tttcttcttc cgtattaaca gcactttttt ctcttggaaa gaaagt 46

&lt;210> 1004 &lt;211> 46 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400&gt; 1004 agagaaggat aactgaccga cttctttttt ctcttggaaa gaaagt 46 &lt;210&gt; 1005 &lt;211&gt; 43 505 - 152219 - Sequence Listing.doc 201130494 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223&gt; 223> Description of Artificial Sequence: bDNA Probe of MAN2A1 &lt; 400> 1005 agaattcacc ttgcagctca agtttttctc ttggaaagaa agt 43 &lt;210&gt; 1006 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400&gt; 1006 tgcccacctt tgactgtatt gttttttctc ttggaaagaa agt 43 &lt;210&gt; 1007 &lt;211> 42 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> MAN2A1 bDNA probe

&lt;223> Description of artificial sequence

&lt;400&gt; 1007 cttttcggat gtccacaata ttgtttttga agttaccgtt tt 42 &lt;210> 1008 &lt;211> 44 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1008 ttcattgcaa tctcacggtt atatattttt ctgagtcaaa gcat 44 •506- 152219·sequence table.doc 201130494 &lt;210> 1009 &lt;211&gt; 47 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of the artificial sequence: bDNA probe for MAN2A1 &lt;400> 1009 tacccattta ggtcagtata aaatctattt tttgaagtta ccgtttt 47

&lt;210> 1010 &lt;211> 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1010 cagtgtcatt ctaggttgaa tctggttttt ctgagtcaaa gcat 44 &lt;210&gt; 1011 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1011 cattgtggtc atgggataga catttttttg aagttaccgt ttt 43 &lt;210&gt; 1012 &lt;211&gt; 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 • 507· 152219-sequence table.doc 201130494 &lt;400&gt; 1012 tttggcatcc tggatatagg ctttttctga gtcaaagcat 40 &lt;210> 1013 &lt;211&gt; 42 &lt;212&gt; DNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: :bDNA probe of MAN2A1 &lt;400&gt; 1013 aactcgaaac ccctaatgac tgatttttga agttaccgtt tt 42 &lt;210&gt; 1014 &lt;211&gt; 46 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: :bDNA probe of MAN2A1 &lt;400&gt; 1014 tgataacttc aatctgacca ctattcattt ttctgagtca aagcat 46 &lt;210&gt; 1015 &lt;211&gt; 40 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: :BDNA probe of MAN2A1&lt;400&gt; 1015 tgctcaaggc cacgattatc atttttgaag ttaccgtttt 40 &lt;210> 1016 &Lt; 211 > 46 &lt; 212 &gt; DNA &lt; 213 > artificial sequence 508 · 152219 - Sequence Listing. doc 201130494 &lt; 220 > &lt; 223 > description of artificial sequence: bDNA probe of MAN2A1 &lt;400 > 1016 gctgtaatct tgttatcctg Gatacctttt ttctgagtca aagcat 46 &lt;210> 1017 &lt;211> 43 &lt;212> DNA &lt;213>Artificial Sequence&lt;220〉

&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1017 cattggaat-g actggatgat tcattttttg aagttacc-gt ttt 43 &lt;210> 1018 &lt;211> 43 &lt;212> DNA &lt;213> artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1018 ggtaggtgag gagaacttat ttgctttttc tgagtcaaag cat 43

&lt;210> 1019 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of MAN2A1 &lt;400> 1019 aaggcaaaga tgactgtaat ggagtttttg aagttaccgt ttt 43 &lt;210> 1020 &lt; 211 &gt; 211 > 45 509 · 152219 · Sequence Listing. doc 201130494 &lt;212&gt; DNA &lt; 213 > Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: bDNA Probe of MAN2A1 &lt; 400> 1020 tctcaaatta accagatgaa tgtcactttt tctgagtcaa agcat 45 &lt;210> 1021 &lt;211&gt; 38 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400&gt; 1021 gcctcattgg agtgcccatt ttttgaagtt accgtttt 38 &lt;210&gt; 1022 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of MAN2A1 &lt;400 〉 1022 ttttctgtgg aggatcaagg cttttttctg agtcaaagca t 41 &lt;210> 1023 &lt;211> 16 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1023 agggg Ggccc cacact 16 -510-

152219-Sequence List.doc 201130494 &lt;210> 1024 &lt;211> 20 &lt;212> DNA <213> Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence: bDNA Probe of Human KIFC1 &lt;400> 1024 gggactcctt gttgctcagg 20

&lt;210> 1025 &lt; 211 &gt; 211 &gt; 211 &lt; 212 &gt; DNA &lt; 213 &gt; 213 > Artificial Sequence &lt; 220 &lt; 223 &gt; Description of Artificial Sequence: Human KIFC1 bDNA Probe &lt;400> 1025 ctcctcactc cctggccctt ttttctcttg gaaagaaagt 40 &lt;210> 1026 &lt;211> 40 &lt;212> DNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1026 gaagcagggc gtccacttct ttttctcttg gaaagaaagt 40 &lt;210> 1027 &lt;211> 41 &lt;212> DNA &lt;213> Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 - 511 - 152219 - Sequence Listing. doc 201130494 &lt;400&gt; 1027 tgaccgttca ttctgggctg tttttctctt ggaaagaaag t 41 &lt;210> 1028 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1028 gcaggcctcg gctggagttt tttctcttgg aaagaaagt 39

&lt;210&gt; 1029 &lt;211> 38 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1029 gggccgaggg ctaagccttt ttctcttgga aagaaagt 38 &lt;210> 1030

&lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1030 gctgttccgg taaggcacgt tttttctctt ggaaagaaag t 41 &lt;210> 1031 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213&gt; artificial sequence 512-152219. Sequence Listing.doc 201130494 &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1031 tctgcagcag gtaggtcagt tttttttctc ttggaaagaa agt 43 &lt;210> 1032 &lt;211> 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence··bDNA probe of human KIFC1

&lt;400> 1032 cactggttca ccttgga.ggc tttttctctt ggaaagaaag t 41 &lt;210&gt; 1033 &lt;211&gt; 41 &lt;212> DNA <213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA of human KIFC1 Probe &lt;400&gt; 1033 atcgagcatt ggtgacagtg agtttttgaa gttaccgttt ΐ 41

&lt;210&gt; 1034 &lt;211&gt;42 &lt;212&gt;212&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1034 tttctcacag gagacaggga cattttttct gagtcaaagc at 42 &lt;210&gt; 1035 513- 152219 · Sequence Listing.doc 201130494 &lt;211&gt; 37 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human KIFC1 bDNA Probe &lt;400> 1035 gattctggcg ggccagattt tttgaagtta ccgtttt 37 &lt;210> 1036 &lt;211> 34 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1036 tgcgggccac agcccttttt ctgagtcaaa gcat 34 &lt;210> 1037 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1037 gaatacactg tggctgcgtg atttttgaag ttaccgtttt 40 &lt;210&gt; 1038 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1038 gct Ccccaga aatctgtagc tgtttttctg agtcaaagca t 41 -514·

1522丨9· Sequence Listing.doc 201130494 &lt;210&gt; 1039 &lt;211> 39 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human KIFC1 bDNA Probe &lt;;400> 1039 cggccaggtc cacaagactg tttttgaagt taccgtttt 39

&lt;210> 1040 &lt;211> 39 I &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1040 ggggtcaagt cgctcactcc tttttctgag tcaaagcat 39 &lt;210> 1041 &lt;211&gt; 34 &lt;212> DNA &lt;213> artificial sequence

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1041 cgttcccgct ccccgttttt gaagttaccg tttt 34 &lt;210> 1042 &lt;211> 38 &lt;212&gt; DNA &lt;213&gt;&lt;220>&lt;223> Description of artificial sequence: bDNA probe of human KIFC1 - 515- 152219 - Sequence Listing.doc 201130494 &lt;400> 1042 ggcctgtgtt tcccgaaggt ttttctgagt caaagcat 38 &lt;210> 1043 &lt;211&gt; 40 &lt ;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1043 cgtggacagg ctgctgttaa ttttttgaag ttaccgtttt 40 &lt;210&gt; 1044 &lt;211&gt;;212>DNA&lt;213>Artificialsequence&lt;220>&lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1044 gccatgataa ccagccccag tttttctgag tcaaagcat 39 &lt;210&gt; 1045 &lt;211&gt;;212>DNA&lt;213>Artificialsequence&lt;220>&lt;223> Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1045 tcttagcact accacccaga gagttttttg aagttaccgt ttt 43 &lt;210&gt; 1046 &lt;2 11> 43 &lt;212&gt; DNA &lt;213&gt; artificial sequence 516-152219. Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1046 gagaaatgtt cacaaacatg agcatttttc Tgagtcaaag cat 43 &lt;210> 1047 &lt;211> 40 &lt;212> DNA &lt; 213 &gt; artificial sequence &lt; 220 &gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400&gt; 1047 cggagacgtt ctcttccagt gtttttgaag ttaccgtttt 40 &lt;210> 1048 &lt;211> 42 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human KIFC1 &lt;400> 1048 aaagcgtaga gagttgaggg acttttttct gagtcaaagc at 42 &lt;210> 1049 &lt;211> 19 &lt;212> DNA &lt;213>Artificial sequence &lt;220 〉 &lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1049 ccccctgcct gatagtccc 19 -517- 152219 · Sequence Listing.doc 201130494 &lt;210&gt; 1050 &lt;211> 20 &lt;212> DNA &lt ;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1050 ccctcagagt tccttccccc 20 &lt;210&gt; 1051 &lt;211> 23 &lt;212> DNA &lt;213 〉Artifical sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1051 tcccttttca tcattaacct get 23 &lt;210&gt; 1052 &lt;211> 22 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1052 cctgagagtc cgccctattc tc 22 &lt;210> 1053 &lt;211> 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt; 223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1053 -518·

152219-Sequence table.doc 201130494 actttcagag ccttcattct ggttttttct cttggaaaga aagt 44 &lt;210&gt; 1054 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Human ARHGEF5 bDNA probe &lt;400&gt; 1054 gacctcctgg ggatgcaagt ttttctcttg gaaagaaagt 40

&lt;210&gt; 1055 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1055 tgttcctgtt tttgcttctg ttctttttct cttggaaaga aagt 44 &lt;210> 1056 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1056 ccctctggct ccccagtgat ttttctcttg gaaagaaagt 40 &lt;210> 1057 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence&lt;220> 519- 152219-SEQ ID NO: doc 201130494 &lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1057 ggacctccct gaccctgagc tttttctctt. ggaaagaaag t 41 &lt;210> 1058 &lt;211&gt; 45 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA of human ARHGEF5 Probe &lt;400> 1058 ccaaaaaggt ttgactcttt tcgttttttc tcttggaaag aaagt 45 &lt;210&gt; 1059 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; 223> Description of Artificial Sequence: Human ARHGEF5 bDNA probe &lt;400&gt; 1059 cgctgactgg cacccctttt ttttctcttg gaaagaaagt 40 &lt;210&gt; 1060 &lt;211&gt; 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: Human ARHGEF5 bDNA probe &lt;400&gt; 1060

Gctctttcgc ctcctgcctt tttctcttgg aaagaaagt 39 &lt;210&gt; 1061 &lt;211> 44 &lt;212> DNA 520-

152219 · Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1061 gcagggagaa taatatctgg tctgattttt gaagttaccg tttt 44 &lt;210> 1062 &lt; 211 &gt; 41 &lt;212> DNA &lt; 213 &gt; 213 > Artificial Sequence # &lt; 220 &lt; 223 &gt; 223 > Description of Artificial Sequence: bDNA Probe of Human ARHGEF5 &lt;400> 1062 tggtctctgc aggatgctct tctttttctg agtcaaagca t 41 &lt;210&gt; 1063 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5

&lt;400> 1063 ctcctcaggt ggcagctctt tttttgaagt taccgtttt 39 &lt;210> 1064 &lt;211> 39 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1064 agcccttgac tttcctgcag tttttctgag tcaaagcat 39 -521 - 152219 - Sequence Listing _doc 201130494 &lt;210&gt; 1065 &lt;211&gt; 39 &lt;212&gt; DNA &lt;213&gt; Artificial Sequence &lt;220&gt;&lt;223&gt; Description of the sequence: bDNA probe for human ARHGEF5 &lt;400&gt; 1065 ccctgctcct ccagaacttg tttttgaagt taccgtttt 39

&lt;210> 1066 &lt;211> 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1066 cgaaatcctg cttcctgctg ttttttctga gtcaaagcat 40 &lt;210&gt; 1067 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1067 cccatcggca caaacatcct tttttgaagt taccgtttt 39 &lt;210> 1068 &lt;211&gt; 44 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1068 152219 - Sequence Listing. Doc -522- 201130494 ctatcatctg ttcctcccct aatagttttt ctgagtcaaa gcat 44 &lt;210&gt; 1069 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223> Description of Artificial Sequence: bDNA Exploration of Human ARHGEF5 Needle&lt;400&gt; 1069 cccaagcatc acatcttgta cctttttgaa gttaccgttt t 41

&lt;210> 1070 &lt;211&gt; 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400> 1070 gccccattct ttctccttgt cttttttctg agtcaaagca t 41 &lt;210&gt; 1071 &lt;211> 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human ARHGEF5 &lt;400&gt; 1071 tcccactcac cgtcattcag atttttgaag ttaccgtttt 40 &lt;210> 1072 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> 152219· Sequence Listing.doc - 523 - 201130494 &lt;223> Description of Artificial Sequence: bDNA Probe of Human ARHGEF5 Needle &lt;400&gt; 1072 cttcctctcc atatcctcct gctttttctg agtcaaagca t 41 &lt;210> 1073 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223 Description of artificial sequence: bDNA of human ARHGEF5 Probe &lt;400> 1073 ct.cttxctct ctt.ctccctg ttcttttttg aagttaccgt ttt 43 &lt;210> 1074 &lt;211> 38 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223> Description of Artificial Sequence : Human ARHGEF5 bDNA probe &lt;400&gt; 1074 ttctggcacc tgcagctcct ttttctgagt caaagcat 38 &lt;210&gt; 1075 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: Human ARHGEF5 bDNA probe &lt;400&gt; 1075

Tttccagtta cttcctctga ttttcttttt gaagttaccg tttt 44 &lt;210> 1076 &lt;211&gt; 44 &lt;212&gt; DNA -524-152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human ARHGEF5 bDNA probe &lt;400&gt; 1076 ctcctttata ccatgatctt cttgcttttt ctgagtcaaa gcat 44 &lt;210> 1077 &lt;211> 19 &lt;212> DNA &lt;213> artificial sequence

&lt;223&gt; Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1077 ctcctgcacg tgggctctc 19 &lt;210> 1078 &lt;211> 23 <212> DNA &lt;213>Artificial sequence &lt;220&gt; 〉 Description of artificial sequence: bDNA probe of human SETD4

&lt;400&gt; 1078 aagtctctgg aggaagcaaa gaa 23 &lt;210> 1079 &lt;211> 18 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human SETD4 bDNA probe &lt;;400&gt; 1079 tgcaccaagc ccacagca 18 •525· 152219·sequence table.doc 201130494 &lt;210> 1080 &lt;211> 45 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence : bDNA probe of human SETD4 &lt;400&gt; 1080 cgaaataatc atctgtcc-ct cctgtttttc tcttggaaag aaagt 45 &lt;210> 1081 &lt;211> 39 &lt;212> DNA &lt;213> artificial sequence &lt;220&gt;&lt;223&gt; Description of the sequence: bDNA probe of human SETD4 &lt;400> 1081 gcacagcgcc agcagaggtt tttctcttgg aaagaaagt 39 &lt;210&gt; 1082 &lt;211> 44 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; Description of sequence: bDNA probe of human SETD4 &lt;400> 1082 ggtaaaatct ccaggtaagg ctttttttct cttggaaaga aagt 44 &lt;210> 1083 &lt;211> 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of the artificial sequence: person bDNA probes of type SETD4 • 526·

152219 - Sequence Listing.doc 201130494 &lt;400&gt; 1083 aaagatttgg gaagaaggtt cactttttct cttggaaaga aagt 44 &lt;210> 1084 &lt;211> 42 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description: bDNA probe for human SETD4 &lt;400&gt; 1084 tgctcttcag cctttgcttt ttttttctct tggaaagaaa gt 42

&lt;210&gt; 1085 &lt;211> 43 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt;400&gt; 1085 cagaggctgc agagaagaga aatttttctc ttggaaagaa agt 43

&lt;210&gt; 1086 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt;400&gt; 1086 cggctctggt gttgacggtt tttctcttgg aaagaaagt 39 &lt;210> 1087 &lt;211&gt; 40 &lt;212> DNA &lt; 213 &gt; 213 &gt; 152219 - Sequence Listing. doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt; 400> 1087 tgcctgggcc tcaggtacat ttttctcttg gaaagaaagt 40 &lt;210&gt; 1088 &lt;211> 39 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1088 agcaggcaactctcaggcaatttttgaagt taccgtttt 39 &lt;210&gt; 1089 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt; 223> Description of artificial sequence: bDNA probe of human SETD4 &lt;400> 1089 cgaatcactg tgtccgtggt gtttttctga gtcaaagcat 40

&lt;210&gt; 1090 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt;400&gt; 1090 agtaatgtat gcccctaagt agcttttttt gaagttaccg tttt 44 &lt;210&gt; 1091 &lt;211&gt; 40 528- 152219 - Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human SETD4 bDNA Probe &lt;400> 1091 agatggagga ggcttccact ttttttctga gtcaaagcat 40 &lt;210&gt; 1092 &lt;211> 44 &lt;212> DNA &lt;213> Artificial sequence

&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1092 catgcttttc tgaaactaaa aaggtttttt gaagttaccg tttt 44 &lt;210> 1093 &lt;211> 39 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human SETD4 &lt;400> 1093 ccaaagagat cggtgcccag tttttctgag tcaaagcat 39 &lt;210> 1094 &lt;211&gt; 39 &lt;212&gt; DNA &lt;213&gt; Sequence &lt;220> &lt;223&gt; Description of artificial sequence··bDNA probe of human SETD4&lt;400> 1094 cagggcaggt atacgccttg tttttgaagt taccgtttt 39-529- 152219-sequence table.doc 201130494 &lt;210> 1095 &lt;211&gt; 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1095 cacttccggc tccaaacaaa tttttctgag tcaaagcat 39

&lt;210> 1096 &lt;211> 38 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt;400&gt; 1096 tgtcaacagc ctccgcaaat ttttgaagtt accgtttt 38 &lt;210> 1097 &lt;211> 40 &lt;212> DNA &lt;213> artificial sequence

&lt;220&gt;&lt;223&gt; Description of artificial sequence··bDNA probe of human SETD4&lt;400> 1097 gggcactgta gctgaagatg ctttttctga gtcaaagcat 40 &lt;210&gt; 1098 &lt;211> 37 &lt;212> DNA &lt;213〉Artificial Sequence &lt;220> &lt;223> Description of artificial sequence: human SETD4 bDNA probe 152219 - Sequence Listing. doc - 530- 201130494 &lt;400> 1098 gcagaaaggc attcccgctt tttgaagtta ccgtttt 37 <210> 1099 &lt;211> 38 &lt ;212>DNA &lt;213>Artificial sequence&lt;220> &lt;223> Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1099 tgcacaggtg tccggctctt ttttctgagt caaagcat 38

&lt;210> 1100 &lt;211> 38 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human SETD4 &lt;400> 1100 ggtccaggta cggagcgagt ttttgaagtt accgtttt 38

&lt;210&gt; 1101 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human SETD4 &lt;400&gt; 1101 catgtgggct atgattcagc atttttctga gtcaaagcat 40 &lt;210> 1102 &lt;211> 40 &lt;212&gt; DNA &lt;213&gt; artificial sequence 531 - 152219 · Sequence Listing.doc 201130494 &lt;220> &lt;223&gt; Description of artificial sequence: human SETD4 bDNA probe &lt;400> 1102 taaacgctgc Ttttacctgg atttttgaag ttaccgtttt 40 &lt;210> 1103 &lt;211> 46 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human SETD4 bDNA probe &lt;400> 1103 taatttcgta Agaatgagtt tcttcatttt ttctgagtca aagcat 46 &lt;210> 1104 &lt;211&gt; 23 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1104 Taactgggat ggatattgac agg 23 &lt;210&gt; 1105 &lt;211> 23 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human GOLSYN bDNA probe &lt;400> 1105 tgattttcac Cgcaagac At gta 23 &lt;210> 1106 -532-

152219·Sequence List.doc 201130494 &lt;211&gt; 20 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA Probe of Human GOLSYN &lt;400&gt; 1106 ggtttggggg tctgacacca 20

&lt;210> 1107 &lt;211&gt; 20 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1107 ggccagctgg gacttaagct 20 &lt; 210> 1108 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1108 gcctgtgctg ctcgaggatt tttctcttgg aaagaaagt 39 &lt; 210> 1109 &lt;211> 43 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human GOLSYN bDNA probe &lt;400&gt; 1109 tgaagaagaa gaccgcttgc tttttttctc ttggaaagaa agt 43 - 533 - 152219 - Sequence Listing.doc 201130494 &lt;210> 1110 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; 223> Description of Artificial Sequence: bDNA Probe of Human GOLSYN&lt;;400&gt; 1110 catgaggacc tcgattgcgt ttttctcttg gaaagaaagt 40 &lt;210> 1111 &lt;211> 37 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human GOLSYN bDNA probe &lt;;400> 1111 cgcggggatg Atgggctttt tctcttggaa agaaagt 37 &lt;210&gt; 1112 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human GOLSYN bDNA probe &lt;400&gt; 1112 gcttggggaa Gaaggtgcat ttttctcttg gaaagaaagt 40 &lt;210> 1113 &lt;211> 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human GOLSYN bDNA probe-534-

152219· Sequence Listing.doc 201130494 &lt;400&gt; 1113 ccttccagaa cgcctcatga tttttctctt ggaaagaaag t 41 &lt;210> 1114 &lt;211&gt; 43 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Artificial Sequence Description: Human GOLSYN bDNA probe &lt;400&gt; 1114 tccttcagct tggttttgag gttttttctc ttggaaagaa agt 43

&lt;210&gt; 1115 &lt;211&gt; 42 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN&lt;400&gt; 1115 gagtgccaac tgggcctcta ctttttctct tggaaagaaa gt 42 &lt;210> 1116 0 &lt;211> 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1116 tttcacaagg cctgactttg attttttgaa Gttaccgttt t 41 &lt;210&gt; 1117 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213&gt; artificial sequence 535 - 152219 · Sequence Listing.doc 201130494 &lt;220> &lt;223> Description of artificial sequence: bDNA of human GOLSYN Probe &lt;400> 1117 gctaaaatca gcttcactac ctggtttttc tgagtcaaag cat 43 &lt;210> 1118 &lt;211> 38 &lt;212> DNA &lt;213>Artificial Sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400&gt; 1118 cctcaggagc ggaaatgctt ttttgaagtt accgtttt 38 &lt;210> 1119 &lt;211> 38 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1119 cccgcagtcg acatatggat ttttctgagt caaagcat 38

&lt;210> 1120 &lt;211&gt; 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human GOLSYN bDNA probe &lt;400&gt; 1120 cgaagctcca ttactccgcc tttttgaagt taccgtttt 39 &lt;210&gt; 1121 - 536- 152219 · Sequence Listing.doc 201130494 &lt;211&gt; 38 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA Probe of Human GOLSYN &lt;400> 1121 tgctgccagg cttgtgtgat ttttctgagt caaagcat 38

&lt;210> 1122 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1122 catggacaga aggtcctttt cctttttgaa gttaccgttt t 41 &lt;210&gt; 1123 &lt;211> 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human GOLSYN bDNA probe &lt;400&gt; 1123 gctcagctga ttcctgcaca gtttttctga gtcaaagcat 40 &lt;210&gt; 1124 &lt;211> 43 &lt;212> DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN&lt;400&gt; 1124 tttgtaggag cctgagttgc tacttttttg aagttaccgt Ttt 43 • 537- 152219 - Sequence Listing.doc 201130494 &lt;210> 1125 &lt;211> 38 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA of Human GOLSYN Probe &lt;400> 1125 tggggctaca gtcgcttcct ttttctgagt caaagcat 38 &lt;210> 1126 &lt;211> 43 &lt;212> DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA of Human GOLSYN Probe &lt;4 00&gt; 1126 gcagtggagt caaatactgc tctgtttttg aagttaccgt ttt 43 &lt;210> 1127 &lt;211&gt; 43 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human GOLSYN bDNA probe &lt; 400> 1127 gtctcactgt cacctctttc tgcttttttc tgagtcaaag cat 43 &lt;210> 1128 &lt;211> 38 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; <223> Description of artificial sequence: bDNA probe of human GOLSYN • 538 -

152219-Sequence table.doc 201130494 &lt;400&gt; 1128 atggagtcgg cgctcagatt ttttgaagtt accgtttt 38 &lt;210> 1129 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence : bDNA probe for human GOLSYN &lt;400> 1129 ccacgatttc actttccctt tctttttctg agtcaaagca t 41

&lt;210> 1130 &lt;211&gt; 37 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400> 1130 ccagtcctct cgcatgcgtt tttgaagtta ccgtttt 37

&lt;210> 1131 &lt;211> 40 &lt;212> DNA <213> Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GOLSYN &lt;400&gt; 1131

Ccggtgacac tcctcctcaa ttttttctga gtcaaagcat 40 &lt;210&gt; 1132 &lt;211> 16 &lt;212> DNA 539· 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human PLEKHA3 bDNA probe &lt;400> 1132 tggagcttgg gggccg 16 &lt;210> 1133 &lt;211> 14 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA of human PLEKHA3 Probe &lt;400&gt; 1133 gcccgggccc cctc 14 &lt;210&gt; 1134 &lt;211> 13 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; 223 Description of Artificial Sequence: Human PLEKHA3 bDNA Probe &lt;400&gt; 1134 cccggcgccg gcc 13 &lt;210&gt; 1135 &lt;211> 20 &lt;212> DNA &lt; 213 &gt; 213 &gt; 221 &gt; 223 &lt; 223 &gt; 223 &gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt; 400> 1135 catgcttcag agccccacac 20 - 540-

152219-Sequence List.doc 201130494 &lt;210> 1136 &lt;211> 21 &lt;212> DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human PLEKHA3 bDNA Probe &lt;400&gt;; 1136 ccacttgtac aacaccccct c 21

&lt;210&gt; 1137 &lt;211&gt;22 &lt;212&gt; DNA &lt;213&gt; artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1137 gccatcttta tgcttccttt gc 22 &lt 210> 1138 &lt;211&gt; 2δ &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1138 agtccttgta tcagtcaaac atgct 25 &lt; 210> 1139 &lt;211> 27 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1139 • 541 · 152219 - Sequence Listing .doc 201130494 ggtttcactt atttcttttt ctttttt 27 &lt;210&gt; 1140 &lt;211> 35 &lt;212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Human PLEKHA3 bDNA Probe &lt;400 〉 1140 cagcgggcgc agcgtttttc tcttggaaag aaagt 35 &lt;210> 1141 &lt;211&gt; 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human PLEKHA3 bDNA probe &lt;400&gt;; 1141 ggcctttaga ggccgggatt tttctcttgg Aaagaaagt 39 &lt;210> 1142 &lt;211&gt; 36 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1142 cgccggcacg aagccttttt ctcttggaaa Gaaagt 36 &lt;210&gt; 1143 &lt;211&gt; 35 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;

152219 · Sequence Listing.doc 201130494 &lt;223> Description of Artificial Sequence: bDNA probe of human PLEKHA3 &lt;400&gt; 1143 gcccctcccg gccctttttc tcttggaaag aaagt 35 &lt;210&gt; 1144 &lt;211&gt; 36 &lt;212> DNA &lt;213 〉Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3

&lt;400> 1144 cgcgcatcct cccggttttt ctcttggaaa gaaagt 36 &lt;210> 1145 &lt;211&gt; 48 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400〉 1145 gctgaatgaa ctttaatttc acaaactttt ttctcttgga aagaaagt 48

&lt;210&gt; 1146 &lt;211> 43 &lt;212&gt; DNA &lt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400&gt; 1146 gctgcattca ctgccttcat gttttttctc ttggaaagaa a , gt 43

&lt;210&gt; 1147 &lt;211&gt; 43 &lt;212&gt; DNA 543 - 152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human PLEKHA3 bDNA Probe &lt; 400> 1147 ttttggtttt cagcgattca cttttttctc ttggaaagaa agt 43 &lt;210&gt; 1148 &lt;211&gt; 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1148 agacattccc gggtaagcct tttttgaagt t.accgtttt 39 &lt;210&gt; 1149 &lt;211> 33 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA of human PLEKHA3 Probe &lt;400&gt; 1149 cgaggcgcgg gccctttttc tgagtcaaag cat 33 &lt;210> 1150 &lt;211&gt; 35 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA of human PLEKHA3 Probe &lt;400> 1150 gccgcaggga cgtggctttt tgaagttacc gtttt 35 -544-

152219·Sequence list.doc 201130494 &lt;210> 1151 &lt;211&gt; 36 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human PLEKHA3 bDNA probe &lt;400&gt;; 1151 gctttctgcc tgcgcgcttt ttctgagtca aagcat 36

&lt;210&gt; 1152 &lt;211> 34 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1152 gcagggcctg gggcattttt gaagttaccg tttt 34 &lt;210&gt; 1153 &lt;211&gt; 36 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1153 gcggtgatgg ggtaggcttt ttctgagtca aagcat 36 &lt;210&gt; 1154 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400&gt; 1154 •545 · 152219- Sequence Listing.doc 201130494 gccagcctgt gagatagttg gttttttgaa gttaccgttt t 41 &lt;210> 1155 &lt;211&gt; 41 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; 223 Description of artificial sequence: bDNA probe of human PLEKHA3 Needle &lt;400&gt; 1155 tctaaaacaa accaacgagg cttttttctg agtcaaagca t 41 &lt;210> 1156 &lt;211> 47 &lt;212&gt; DNA &lt;213&gt; artificial sequence&lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA of human PLEKHA3 Probe &lt;400&gt; 1156 tgaatcatag taggataaga ttccattatt tttgaagtta ccgtttt 47 &lt;210&gt; 1157 &lt;211> 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: bDNA probe of human PLEKHA3 Needle &lt;400> 1157 tccctttgca aacatcatct tgtttttctg agtcaaagca t 41 &lt;210> 1158 &lt;211&gt; 45 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;

152219-Sequence List.doc 201130494 &lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1158 tgattaattc cattcttgtg ttgtcttttt tgaagttacc gtttt 45 &lt;210> 1159 &lt;211> 40 &lt;212> DNA &lt; 213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3

&lt;400> 1159 agaaatgctg ctctccagga atttttctga gtcaaagcat 40 &lt;210&gt; 1160 &lt;211> 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400&gt; 1160 accagccacc tctgtctttc atttttgaag ttaccgtttt 40

&lt;210> 1161 &lt;211> 37 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1161 ttggagctcc ccagagcgtt tttctgagtc aaagcat 37

&lt;210&gt; 1162 &lt;211&gt; 43 &lt;212> DNA 547-152219 - Sequence Listing.doc 201130494 &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: Human PLEKHA3 bDNA Probe &lt; 400> 1162 cacagtagag gcgaagttca gacatttttg aagttaccgt ttt 43 &lt;210> 1163 &lt;211> 43 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human PLEKHA3 &lt;400> 1163 tatgaacttg ctgcattaag aggttttttc tgagtcaaag cat 43 &lt;210&gt; 1164 &lt;211&gt; 29 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1164 cattcaaatt tcttatgact gataattta 29 &lt;210&gt; 1165 &lt;211&gt; 24 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 1165 cttggtcaat gaagagaact tggt 24 •548-

152219 - Sequence Listing.doc 201130494 &lt;210&gt; 1166 &lt;211&gt; 42 &lt;212&gt;&lt;212&gt;&gt;213&gt;&lt;223&gt;&lt;223&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;;400> 1166 ccgctttagc agccagagtt gtttttctct tggaaagaaa gt 42

&lt;210> 1167 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1167 tagactgcag caggtggcag tttttctctt Ggaaagaaag t 41 &lt;210&gt; 1168 &lt;211> 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1168 Aatagtttgt tgcgagagga agctttttct cttggaaaga aagt 44 &lt;210> 1169 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt; Human IL-18 bDNA probe • 549· &lt;223> Description of artificial sequence 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 1169 atcttcaaat agaggccgat ttctttttct cttggaaaga aagt 44 &lt;210> 1170 &lt;211> 48 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223>Artificial Sequence Description: Human IL-18 bDNA probe &lt;400> 1170 cctctaggct ggctatcttt atacatattt ttctcttgga aagaaagt 48

&lt;210> 1171 &lt;211&gt; 48 &lt;212&gt; DNA &lt;213&gt; Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400&gt; 1171 cacttcacag agatagttac agccatattt Ttctcttgga aagaaagt 48 &lt;210&gt; 1172 &lt;211&gt; 40 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human IL-18 bDNA Probe &lt;400> 1172 Tgcactggga gacaattcct ttttttgaag ttaccgtttt 40 &lt;210> 1173 &lt;211> 37 &lt;212&gt; DNA &lt;213> artificial sequence 550-

152219-SEQ ID NO. doc 201130494 &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human IL-18 &lt;400> 1173 gcagccagga gggcaaaatt tttctgagtc aaagcat 37 &lt;210> 1174 &lt;211> 39 &lt; 212> DNA &lt;213>Artificial Sequence&lt;220> &lt;223> Description of Artificial Sequence: Human IL-18 bDNA Probe

&lt;400> 1174 ttcctcttcc cgaagctgtg tttttgaagt taccgtttt 39 &lt;210&gt; 1175 &lt;211> 42 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; 223> Description of artificial sequence: human IL-18 bDNA Probe &lt;400&gt; 1175 gatctggaag gtctgaggtt ccttttttct gagtcaaagc at 42

&lt;210> 1176 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1176 gccatcttta ttcctgcgac atttttgaag Ttccgtttt 40 &lt;210> 1177 &lt;211&gt; 43 551 - 152219 - Sequence Listing.doc 201130494 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: Human IL-18 bDNA probe &lt;400> 1177 caattgtctt ctactggttc agcatttttc tgagtcaaag cat 43 &lt;210> 1178 &lt;211> 42 &lt;212> DNA &lt;213> artificial sequence human 1L-18 bDNA probe

&lt;220> &lt;223&gt; Description of artificial sequence &lt;400&gt; 1178 atttcattgc cacaaagttg atgtttttga agttaccgtt tt 42 &lt;210> 1179 &lt;211> 47 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt; 223> Description of artificial sequence: bDNA probe of human IL-18 &lt;400> 1179 gctataaagt aaagcgtatt gtcaataatt tttctgagtc aaagcat 47 &lt;210&gt; 1180 &lt;211> 43 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;;&lt;223> Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1180 gattccaggt tttcatcatc ttcatttttg aagttaccgt ttt 43 -552-

152219 · Sequence Listing. doc 201130494 &lt;210&gt; 1181 &lt;211&gt; 43 &lt;212&gt; DNA &lt;213&gt; Artificial Sequence &lt;220&gt; <223> Description of Artificial Sequence: Human IL-18 bDNA Probe &lt;400&gt; 1181 gattcaagct tgccaaagta atcttttttc tgagtcaaag cat 43

&lt;210&gt; 1182 &lt;211> 48 0 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human IL-18 bDNA probe &lt;400> 1182 gcattatctc tacagtcaga Atcagtcatt ttttgaagtt accgtttt 48 &lt;210> 1183 &lt;211> 43 &lt;212&gt; DNA &lt;213> artificial sequence

&lt;223&gt; Description of artificial sequence: bDNA probe of human IL-18 &lt;400> 1183 cttataataa atatggtccg gggttttttc tgagtcaaag cat 43 &lt;210&gt; 1184 &lt;211&gt; 23 &lt;212> DNA &lt;213>Artificial sequence &lt; 220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH - 553 · 152219 - Sequence Listing.doc 201130494 &lt;400&gt; 1184 ggcaacaata tccactttac cag 23 &lt;210&gt; 1185 &lt;211> 20 &lt;212 〉 DNA &lt; 213 > Artificial Sequence &lt; 220 > &lt; 223 > Description of Artificial Sequence: bDNA Probe for Human GAPDH &lt;400&gt; 1185 gacgtactca gcgccagcat 20

&lt;210> 1186 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 1186 gaggctgcgg gctcaatttt tttctcttgg aaagaaagt 39 &lt;210> 1187 &lt;211> 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 1187 tggcgacgg aaagaagatg tttttctctt ggaaagaaag t 41 &lt;210> 1188 &lt;211&gt; 42 &lt;212&gt; DNA &lt;213&gt; artificial sequence • 554 -

152219 - Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: bDNA probe for human GAPDH &lt;400&gt; 1188 caaatccgtt gactccgacc ttttttctct tggaaagaaa gt 42 &lt;210&gt; 1189 &lt;211&gt; 43 &lt;212&gt ; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223> Description of artificial sequence: bDNA probe of human GAPDH

&lt;400> 1189 ggtcaatgaa ggggtcattg attttttctc ttggaaagaa agt 43 &lt;210> 1190 &lt;211&gt; 41 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH Needle &lt;400> 1190 ccttgacggt gccatggaat tttttctctt ggaaagaaag t 41

&lt;210&gt; 1191 &lt;211&gt; 41 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 1191 aagacgccag tggactccac tttttctctt ggaaagaaag t 41 &lt;210> 1192 555 - 152219 · Sequence Listing.doc 201130494 &lt;211> 38 &lt;212&gt; DNA &lt;213>Artificial Sequence &lt;220> &lt;223> Description of Artificial Sequence: bDNA needle of human GAPDH &lt;400&gt; 1192 ggagcagaga gcgaagcggt ttttgaagtt accgtttt 38

&lt;210&gt; 1193 &lt;211>39 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 1193 cggctgact.g tcgaacagga tttttctgag Tcaaagcat 39 &lt;210&gt; 1194 &lt;211> 36 &lt;212&gt; DNA &lt;213>Artificial Sequence&lt;220&gt;

&lt;223&gt; Description of artificial sequence: bDNA probe for human GAPDH &lt;400&gt; 1194 gagcgatgtg gctcggcttt ttgaagttac cgtttt 36 &lt;210> 1195 &lt;211> 39 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400&gt; 1195 tcaccttccc catggtgtct tttttctgag tcaaagcat 39 152219. Sequence Listing. doc - 556 - 201130494 &lt;210&gt; 1196 &lt;211> 37 &lt;212> DNA &lt;213>Artificial sequence &lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe for human GAPDH &lt;400&gt; 1196 ccaggcgccc aatacgactt tttgaagtta ccgtttt 37

&lt;210> 1197 &lt;211> 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 1197 agttaaaagc agccctggtg atttttctga gtcaaagcat 40 &lt;210> 1198 &lt;211&gt; 44 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 1198 tggaacatgt aaaccatgta gttgattttt gaagttaccg tttt 44 &lt;210> 1199 &lt;211&gt; 40 &lt;212> DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; Description of artificial sequence: human GAPDH bDNA probe 152219 - Sequence Listing. doc - 557- 201130494 &lt;400&gt; 1199 ttgccatggg tggaatcata ttttttctga gtcaaagcat 40 &lt;210> 1200 &lt;211&gt; 40 &lt;212&gt; DNA &lt;213>Artificial sequence &lt;220> &lt;223&gt; 223> Description of artificial sequence: bDNA probe of human GAPDH Needle &lt;400&gt; 1200 tgacaagctt cccgttctca gtttttgaag ttaccgtttt 40

&lt;210> 1201 &lt;211&gt; 40 &lt;212&gt;&gt;213&gt;213>Artificial sequence&lt;220&gt;&lt;223&gt; Description of artificial sequence: bDNA probe of human GAPDH&lt;400&gt; 1201 tggtgatggg atttccattg atttttctga gtcaaagcat 40 &lt;210> 1202 &lt;212> DNA <213>Artificial sequence &lt;220> &lt;223> Description of artificial sequence: bDNA probe of human GAPDH &lt;400> 1202 gggatctcgc tcctggaaga tttttgaagt taccgtttt 39 &lt;210&gt; 1203 &lt;;211> 38 &lt;212> DNA &lt;213>Artificial Sequence 558-

152219-Sequence Listing.doc 201130494 &lt;220&gt;&lt;223&gt; Description of Artificial Sequence: bDNA Probe for Human GAPDH &lt;400&gt; 1203 cgccccactt gattttggat ttttctgagt caaagcat 38

559- 152219 · Sequence Listing. doc

Claims (1)

201130494 VII. Scope of Application: 1. A double-stranded ribonucleic acid molecule capable of exhibiting at least 60%, preferably at least 70% and optimally at least 80% inhibition of the IL_18 gene in vitro. 2. The double-stranded ribonucleic acid molecule of claim 1, wherein the double-stranded ribonucleic acid molecule comprises a sense stock and an anti-sense stock 'the anti-sense stock is at least partially complementary to the sense stock' thereby thereby At least a portion of the mRNA encoding IL-18 has at least 90% identical sequence, wherein the sequence (1) is in a region of the sense strand complementary to the antisense strand; and (ii) wherein the sequence is less than 30 in length Nucleotide. 3. The double-stranded ribonucleic acid molecule of claim 2, wherein the sense strand comprises the nucleotide sequence described by SEQ ID Nos: 1, 3, 7, 9, 13, 15, 17, 19, 27 and 31, And the antisense strand comprises the nucleic acid sequence described by SEQ ID No: 2, 4, 8, 10, 14, Ιό, 18, 20, 28 and 32, wherein the double-stranded ribonucleic acid molecule comprises a SEQ ID NO: Paired sequences of groups consisting of 1/2, 3/4, 7/8, 9/10, 13/14, 15/16, 17/18, 19/20, 27/28, and 31/32. 4. The double-stranded ribonucleic acid molecule of claim 3, wherein the antisense strand further comprises a 3' exon (overhang) of 1 to 5 nucleotides in length, preferably 1 to 2 nucleotides in length. 5. The double-stranded ribonucleic acid molecule of claim 4, wherein the exon of the antisense strand comprises uracil or a nucleotide complementary to the mRNA encoding IL-18. The double-stranded ribonucleic acid molecule according to any one of claims 3 to 5, wherein the sense strand further comprises 丨 to 5 nucleotides in length, preferably 丨 to 2 nucleotides 152219.doc 201130494 in length 3' Protrusion β 7. The double-stranded ribonucleic acid molecule of claim 6, wherein the overhang of the sense strand comprises uracil or a nucleotide associated with the mRNA encoding IL-18. 8. The double-stranded ribonucleic acid molecule of any one of claims 1 to 5, wherein the double-stranded ribonucleoside molecule comprises at least one modified nucleotide. 9. The double-stranded ribonucleic acid molecule of claim 8, wherein the modified nucleotide is selected from the group consisting of: 2, _〇-methyl modified nucleotide, 5, _〇_methyl modified a nucleotide, a nucleotide comprising a 5,-thiophosphate group, and a terminal nucleus acid, 2,-deoxyfluorinated, attached to a cholesteryl derivative or a bis-decyl guanidinoamine Nucleotide, 2, fluorine modified nucleotide, locked nucleotide, abasic nucleotide, 2ι_amine modified nucleotide, 2,_alkyl modified Nucleic acid, N-morpholino nucleotide, phosphoramidate, 5'-phosphate group at the 5' end of the antisense strand, and core containing non-natural testosterone Glycosylate. 1 . The double-stranded ribonucleic acid molecule of claim 8, wherein the modified nucleotide is a 21-0-methyl modified nucleotide, a 5,_〇_meryl modified nucleotide, 2, A fluorine-modified nucleotide, a nucleotide comprising a 5, phosphorothioate group, deoxythymidine, and a 5'-phosphate group at the 5' end of the antisense strand. 11. The double-stranded ribonucleic acid molecule of claims 3 to 5, wherein the sense strand and/or the antisense strand comprises a protrusion having from 1 to 2 deoxythymidine. The double-stranded ribose acid molecule according to any one of claims 1 to 5, wherein the double-stranded ribonucleic acid molecule comprises a paired sequence selected from the group consisting of: 152219.doc 201130494 SEQ ID NO: 149/150 , 163/164, 165/166, 179/180, 183/184, 185/186, 187/188, 213/214, 215/216, 217/218, 239/240, 253/254, 255/256, 293 /294, 435/436, 461/462, 463/464, 471/472, 475/476, 479/480 and 487/488 ° 13. a nucleic acid sequence encoding as claimed in any one of claims 1 to 12. A rational and/or antisense strand contained in a double-stranded ribonucleic acid molecule as defined. 14. A vector comprising a regulatory sequence operably linked to at least one of a sense strand or an antisense strand encoded in a double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12. A nucleotide sequence of a strand, or a nucleic acid sequence as claimed in claim 13. A cell, a tissue or a non-human organism comprising the double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12, the nucleic acid molecule of claim 13, or the vector of claim 14. 16. A pharmaceutical composition comprising a double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12, a nucleic acid molecule according to claim 13, a vector according to claim 14 or a cell according to claim 15 Or organization. 17. The pharmaceutical composition of claim 16 further comprising a pharmaceutically acceptable carrier, stabilizer and/or diluent. 18. A method of inhibiting the expression of an IL-18 gene in a cell, tissue or organism in vitro, comprising the steps of: (a) a double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12, The nucleic acid molecule of claim 13, the vector of claim 14 is introduced into the cell, tissue or organism; and 152219.doc 201130494 19. 20.21. 22. (8) maintaining the cell, tissue or organism produced in step (4) is sufficient to achieve The time at which the mRNA transcript of the IL-18 gene is degraded, thereby inhibiting the expression of the IL-1 8 gene in the cell. A double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12, a nucleic acid molecule according to claim 13, a carrier according to claim 14 and/or a pharmaceutical composition as defined in claim 16 or The use thereof for the preparation of a medicament for treating, preventing or managing a pathological condition and disease caused by IL_18&amp; The use of claim 19, wherein the individual is a human. A divalent ribonucleic acid molecule as defined in any one of claims 1 to 12, a nucleic acid molecule according to claim 13, a carrier according to claim 14 and/or a pharmaceutical composition as claimed in claim 16 or 17, It is used for autoimmune diseases and inflammatory diseases. A use of a double-stranded ribonucleic acid molecule as defined in any one of claims 1 to 12, a nucleic acid molecule of claim 13, a vector of claim 14 and/or a cell or tissue of claim 15 It is used to prepare a pharmaceutical composition for treating autoimmune diseases and inflammatory diseases. 1522I9.doc