CN117897482A

CN117897482A - Compositions and methods for treating cancer

Info

Publication number: CN117897482A
Application number: CN202280058799.2A
Authority: CN
Inventors: 戴维·J.·埃尔齐; 威廉·E.·鲍塔; 薇薇安·I.·里贝尔
Original assignee: Biological Afiniti Technology Co ltd
Current assignee: Biological Afiniti Technology Co ltd
Priority date: 2021-06-28
Filing date: 2022-01-26
Publication date: 2024-04-16
Also published as: WO2023277959A1; CA3174172A1

Abstract

A double-stranded RNA interference (RNAi) agent comprising at least one of: (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein the first dsRNA comprises a duplex-forming sense strand and an antisense strand, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein the second dsRNA comprises a duplex-forming sense strand and an antisense strand, or (iii) a mixture of (i) and (ii), and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA, and the use of an RNAi agent as a pharmaceutical composition for treating cancer in a subject in need of treatment.

Description

Compositions and methods for treating cancer

Cross Reference to Related Applications

The present application claims the priority and benefit of U.S. patent application Ser. No. 17/359,905, entitled "compositions and methods for treating cancer," filed on 6/28 of 2021. The specification and claims of this U.S. patent application are incorporated herein by reference.

Sequence listing

The present application comprises a sequence listing that has been submitted electronically in ASCII format and is incorporated herein by reference in its entirety. The ASCII copy was created at 26 months 1 of 2022, named 32064-1035-PCT2_SL.txt, of size 446,054 bytes.

Background

There are various cancer therapies and treatments, such as surgical excision of solid tumors, radiation therapy and chemotherapy. Although surgical resection and radiation therapy are used for localized tumors, chemotherapy is often delivered systemically and affects both cancerous and non-cancerous cells, resulting in serious and even life threatening side effects. Older cancer drugs, including alkylating agents, nucleotide antimetabolites and tubulin poisons, have significant side effects because they are toxic to normal cells similar to cancer cells, especially those that undergo conventional cell division in the intestines, scalp and skin. Thus, most efforts in contemporary Cancer Drug Discovery have been directed to finding targeted therapies that distinguish between Cancer cells and normal cells (Neidle et al., (2014) Cancer Drug DESIGN AND Discovery). This has led to drugs that inhibit the function of oncolytic proteins that are mutated, over-expressed or abnormally overactive in cancer but not mutated, over-expressed or abnormally overactive in normal cells. Examples of such drugs include kinase inhibitors, histone deacetylase inhibitors, proteasome inhibitors, mTOR inhibitors, BCL2 inhibitors, and isocitrate dehydrogenase inhibitors. Much effort has also been devoted to targeting cell surface antigens that are differentially expressed in cancer cells compared to normal cells. Thus, monoclonal antibodies and antibody-drug conjugates that target cancer cell surface antigens have been developed as cancer therapeutics (beck et al, (2017) Nat Rev Drug Disc, 16, 315-337). Another point of differentiation between cancer cells and normal cells is metabolism. Many years ago, it was found that many cancer cells utilize glucose fermentation to produce ATP, as opposed to oxidative phosphorylation processes used by normal cells. The FDA recently approved a drug targeting isocitrate dehydrogenase, involving abnormal glucose metabolism in cancer cells (Dhillon (2018) Drugs 78, 1509-1516). Abnormalities in single carbon metabolism, including folate and methionine circulation and affecting nucleotide synthesis and DNA methylation as a way of controlling gene expression, are closely related to some cancers (Fanidi et al., (2019) Int J Cancer 145,1499-1503; yang (2018) Front Oncol 8,493). In this regard, it has long been known that certain synthetic analogs of folic acid (folic acid antagonists) can inhibit the growth of cancer cells. It is also known that the survival of some cancer cells depends on the amino acid methionine. If methionine is restricted, the cancer cells die, which has little effect on normal cells. In recent years, evidence has shown that some cancer cells may have abnormal dependence on vitamin B12. The nature of this dependence is not understood, but may involve to some extent the use of vitamin B12 as a catalytic cofactor by methionine synthase in single carbon metabolism.

Vitamin B12 (cobalamin) is an essential micronutrient in the human diet. It is a cofactor for the metabolic enzymes methionine synthase and methylmalonyl CoA mutase (Fedosov et al., (2012) Water Soluble Vitamins (book) 56, 347-367). After oral administration and intestinal transit, cobalamin binds almost completely to chaperonin-transcobalamin 1 (TCN 1, haptoglobin, R-conjugate) (tco1_human) and transcobalamin 2 (TCN 2) (tco2_human) proteins in plasma. The TCN2 cobalamin complex (TCN 2-Cbl) is taken up by most cells using receptor-mediated endocytosis with a plasma half-life of 1-15h. TCN2 has high affinity and specificity for cobalamins in their various dietary and nutritional supplements, such as methylcobalamin, adenosyl cobalamin and cyanocobalamin (Fedosov et al, (2007) Biochem 46, 6446-6458). TCN1 is a glycoprotein present in plasma in two different forms (Marzolo AND FARFAN (2011) Biol Res 44,81-105). The most abundant form is sialylated and has a plasma half-life of about 10 days (Bor (2004) Clin Chem 50, 1043-1049). One less abundant form is desialylated and has a plasma half-life of a few minutes. Unlike TCN2-Cbl, which is capable of being taken up by almost all cell types, the transcobalamin-1-cobalamin complex (TCN 1-Cbl) is rapidly taken up by certain hepatocytes in its desialylated form via receptor-mediated endocytosis.

CD320 and LRP2 are two receptors involved in uptake of cobalamin in the form of TCN 2-Cbl. CD320 is a member of the Low Density Lipoprotein Receptor (LDLR) family, is constitutively expressed in most cells, and is a receptor responsible primarily for cobalamin uptake (Quadros (2013) Biochimie 95, 1008-1018). CD320 is overexpressed in certain types of cancer (Sycel et al., (2013) ANTICANCER RES 33,4203-4212; amagaasaki (1990) Blood 76, 1380-1386). There is also evidence that CD320 promotes transport of TCN2-Cbl across the blood brain barrier into the brain (Lai et al; 2013) FASEB 27, 2468-2475. LRP2 is another receptor in the LDLR family. It is expressed highest in the kidney but also in other tissues. In addition to cobalamin, LRP2 also transports a variety of proteins and small molecules including albumin, insulin and vitamin D (Mazolo et al., (2011) Biol Res 44,89-105). In the liver, as long as TCN1 is in an desialylated form, the asialoglycoprotein receptor (ASGR) ingests TCN1-Cbl by receptor-mediated endocytosis. Normal hepatocytes and cancer cells express very high levels of ASGR (about 50000 receptors per cell), making this receptor attractive as a portal for drug delivery to the liver (Luo et al.,(2017)Biomedicine and Pharmacotherapy 88,87-94;Stockert(1995)Physiological Rev 75,595-609;Soda et al.,Blood(1985)65,795-802).

Following receptor-mediated endocytosis, cobalamin is sequestered in endosomes where endosomal membranes prevent passive excretion into the cytosol. Specialized proteins (cblF) promote the transport of cobalamins through endosomal membranes to the cytosol (banerjee et al, (2009) Curr Opin Chem Bio, 484-491).

Disclosure of Invention

One embodiment of the present invention provides a double stranded RNA interference (RNAi) agent comprising at least one of the following: (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein the first dsRNA comprises a duplex-forming sense strand and an antisense strand, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein the second dsRNA comprises a duplex-forming sense strand and an antisense strand, or (iii) a mixture of (i) and (ii), and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA, and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA. For example, the antisense strand of (i) the first dsRNA comprises a region of complementarity to a CD320RNA transcript, and for example, the sense strand of (i) the second dsRNA is selected from table 5. (ii) The antisense strand of the second dsRNA comprises a region of complementarity to an LRP2 RNA transcript, and (ii) the sense strand of the first dsRNA is selected from table 6. In one example, (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 16-30 nucleotide pairs in length. In another example, (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 21-23 nucleotide pairs in length. In one embodiment, the double stranded RNAi agent comprises at least one strand of: (i) The first dsRNA or (ii) the second dsRNA comprising a 3' overhang of at least 2 nucleotides. Still further, in one example, the antisense strand of (i) the first dsRNA comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmC mAmGmUmUmCdT*dT(SEQ ID NO 19)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmC mAmGmUmUmC(SEQ ID NO 21)；

mCmAmGmUmUmGmCmGmCmAmGmUmUmUmCmUmUmGmUmC mAmGmUmUmCdT*dT(SEQ ID NO 23)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2f CmA2fGmU2fUmCdT*dT(SEQ ID NO 24)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2f CmA2fGmU2fUmC(SEQ ID NO 25)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUm C2fAmG2fUmU2fCdT*dT(SEQ ID NO 28)；

2fCmA2fGmU2fUmG2fCmG2fCmA2fGmU2fUmU2fCmU2fUmG2fUm C2fAmG2fUmU2fC(SEQ ID NO 29)；

mC2fA2fG2fU2fU2fG2fC2fG2fC2fA2fG2fU2fU2fU2fC2fU2fU2fG2fU2fC2fA2fG2fU2fU2fCdT*dT(SEQ ID NO 30)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2f CmA2fGmU2fUmCdT*dT(SEQ ID NO 32)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fUmU2fGmU2fCmA2fGmU(SEQ ID NO 33)；

mC2fAmG2fUmU2fGmC2fGmC2fAmG2fUmU2fUmC2fU2fU2fG2fU2fC2fA2fG2fU(SEQ ID NO 34)；

Wherein mA, mC, mG and mU are respectively 2' -O-methyladenosine, cytidine, guanosine or uridine; 2fA, 2fC, 2fG and 2fU are 2' -fluoroadenosine, cytidine, guanosine or uridine, respectively; and is a phosphorothioate linkage; and

The sense strand is at least substantially complementary to the antisense strand.

Still further, in another embodiment, the double stranded RNAi agent comprises (i) the antisense strand of the first dsRNA comprising a nucleotide sequence (5 '→3') selected from the group consisting of:

AAGAGCUCAGGUCUCUGAGGGdTdT(SEQ ID NO 64)；

AAGAGCUCAGGUCUCUGAGGGdT*dT(SEQ ID NO 65)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmGdT*dT(SEQ ID NO 66)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmGmG(SEQ ID NO 68)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmGdT*dT(SEQ ID NO 71)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmG(SEQ ID NO 72)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 75)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 76)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fG(SEQ ID NO 77)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 78)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGmG2fGdT*dT(SEQ ID NO 79)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fC2fU2fG2fA2fG2fG2fG(SEQ ID NO 81)；

In another embodiment, the (ii) the second dsRNA of the double stranded RNAi agent comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

mUm[mUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmCdT*dT(SEQ ID NO:419)；

mUmUmUmGmAmUmAmGmCmAmCmCmAmAmAmCmCmUmAmGmAmGmCmCmC(SEQ ID NO:421)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT](SEQ ID NO:424)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmC(SEQ ID NO:425)；

mU2fAmU2fCmA2fAmA2fCmC2fUmC2fGmA2fUmA2fGmC2fAmA2fCmA2fCmC2fGmC(SEQ ID NO:429)；

mU2fU2fU2fG2fA2fU2fA2fG2fC2fA2fC2fC2fA2fA2fA2fC2fC2fU2fA2fG2fA2fG2fC2fC2fCdT*dT(SEQ ID NO:430)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC2fCmCdT*dT(SEQ ID NO:432)；

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fCmC2fUmA2fGmA2fGmC (SEQ ID NO: 433); and

mU2fUmU2fGmA2fUmA2fGmC2fAmC2fCmA2fAmA2fC2fC2fU2fA2fG2fA2fG2fC(SEQ ID NO:434)

In another embodiment, the antisense strand of (ii) the second dsRNA of the double stranded RNAi agent comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

UUUGCAAUGACUCUCCUAUCAGUCCdTdT(SEQ ID NO:448)；

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmCdT*dT(SEQ ID NO:450)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmC(SEQ ID NO:452)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:455)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmC(SEQ ID NO:456)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fCmU2fCmC(SEQ ID NO:458)；

2fUmU2fUmG2fCmA2fAmU2fGmA2fCmU2fCmU2fCmC2fUmA2fUmC2fAmG2fUmC2fCdT*dT(SEQ ID NO:459)；

mU2fAmU2fCmC2fUmA2fAmG2fUmC2fAmC2fAmC2fGmU2fUmU2fGmA2fCmU2fGmC(SEQ ID NO:460)；

mU2fU2fU2fG2fC2fA2fA2fU2fG2fA2fC2fU2fC2fU2fC2fC2fU2fA2fU2fC2fA2fG2fU2fC2fCdT*dT(SEQ ID NO:461)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU2fCmCdT*dT(SEQ ID NO:463)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU(SEQ ID NO:464)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fC2fU2fA2fU2fC2fA2fG2fU(SEQ ID NO:465)

For example, when the RNAi agent comprises (iii) a combination of (i) the first dsRNA and (ii) the second dsRNA, the antisense strand of (i) the first dsRNA is selected from the group consisting of:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

AAGAGCUCAGGUCUCUGAGGGdTdT (SEQ ID NO 64); and

AAGAGCUCAGGUCUCUGAGGGdT x dT (SEQ ID NO 65); and

(Ii) The antisense strand of the second dsRNA is selected from

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

UUUGCAAUGACUCUCCUAUCAGUCCdTdT (SEQ ID NO: 448); and

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

Wherein is a phosphorothioate linkage; and

In one embodiment, (i) the first dsRNA has a duplex structure of (SEQ ID NOS: 17 and 110) or (SEQ ID NOS: 18 and 111). In another embodiment, (ii) the second dsRNA has a duplex structure of (SEQ ID NOS: 417 and 808) or (SEQ ID NOS: 448 and 822).

Another embodiment provides an isolated cell comprising a double stranded RNAi agent of (i), (ii) or (iii).

For example, (i) the sense strand of the first dsRNA is no more than 30 nucleotides in length, and (i) the antisense strand of the first dsRNA is no more than 30 nucleotides in length. For example, (ii) the sense strand of the second dsRNA is no more than 30 nucleotides in length and the antisense strand is no more than 30 nucleotides in length.

Yet another embodiment provides a pharmaceutical composition for inhibiting expression of a CD320 gene, the pharmaceutical composition comprising double stranded RNAi agent (i) or (iii). Furthermore, the pharmaceutical composition may comprise excipients.

Yet another embodiment provides a pharmaceutical composition for inhibiting expression of an LRP2 gene, the composition comprising a double stranded RNAi agent (ii) or (iii). Furthermore, the pharmaceutical composition may comprise excipients.

Another embodiment of the present invention provides a method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with an amount of CD320 additive and/or LRP2 inhibitor effective to inhibit proliferation of the CC. For example, the CC may express CD320 and/or LRP2 or both.

Another embodiment of the invention provides a method for treating a treatment-resistant cancer in a subject previously treated, the method comprising administering to the subject an amount of a CD320 and/or LRP2 inhibitor effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

Another embodiment of the invention provides a method of treating cancer in a subject having recurrent cancer or recurrent cancer comprising administering to the subject an amount of a CD320 and/or LRP2 inhibitor effective to inhibit or kill CC in the cancer.

The CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

The CD320 inhibitor is selected from the group consisting of an antibody that binds to CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

In addition, the method of inhibiting proliferation of CC, treating a treatment-resistant cancer in a subject or a subject with recurrent cancer or recurrent cancer comprises administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding CD320 or an RNAi agent that hybridizes to mRNA encoding LRP 2. For example, the cancer therapeutic agent is selected from antifolate agents, epigenetic modulators, or small molecules of CD320 function or LRP2 function or protein inhibitors such as antibodies to CD320 or antibodies to LRP 2. Furthermore, the method comprises administering metformin. For example, the RNAi agent comprises the antisense strand of table 5 or table 6.

The inhibitor is selected from the group consisting of antibodies that bind to LRP2, small molecule inhibitors of LRP2, and RNAi agents that hybridize to nucleic acid sequences encoding LRP 2. For example, the method further comprises administering a small molecule selected from antifolate agents, epigenetic modulators, or inhibitors of LRP2 function, or a protein inhibitor such as an antibody, in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

The method further comprises administering the cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

One embodiment of the present invention provides a method for inhibiting proliferation of a Cancer Cell (CC), the method comprising contacting the CC with a composition comprising an amount of a CD320 inhibitor and an LRP2 inhibitor effective to inhibit proliferation of the CC, the composition being a mixture comprising i) an antibody selected from the group consisting of CD320 binding, a small molecule inhibitor of CD320 and an RNAi agent hybridized to a nucleic acid encoding CD320, and any combination thereof, and ii) a CD320 inhibitor selected from the group consisting of an antibody binding to LRP2, a small molecule inhibitor of LRP2 and an RNAi agent hybridized to a nucleic acid sequence encoding LRP2, and any combination thereof. In addition, the methods include administering a cancer therapeutic selected from the group consisting of antifolate formulations and epigenetic modulators. For example, the RNAi agent hybridized to the mRNA encoding CD320 comprises a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD320, wherein the first dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region complementary to a CD320RNA transcript, and the RNAi agent hybridized to the mRNA encoding LRP2 comprises a second dsRNA for inhibiting expression of LRP2, wherein the second dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region complementary to an LRP2 RNA transcript. In another example, the antisense strand complementary to a CD320RNA transcript is selected from table 5 and the antisense strand complementary to an RNA transcript of LRP2 is selected from table 6. The method further comprises administering a cancer therapeutic selected from the group consisting of anti-folates and epigenetic modulators. The method further comprises administering a cancer therapeutic selected from the group consisting of immunomodulating. Furthermore, the method comprises administering metformin.

An aspect of one embodiment of the present invention provides a method for inhibiting the expression of CD320 and LRP2 proteins such that their levels in treated cells are reduced compared to the endogenous levels of these proteins in untreated cells; this inhibition may also be referred to as knockdown of CD320 and LRP2 expression. The method requires the use of a mixture of small interfering RNA molecules, also known as siRNA, which direct the mRNA sequences encoding CD320 or LRP2 into the enzyme complex, which results in targeted disruption of these mrnas.

Another aspect of the present invention provides a method for inhibiting LRP2 and CD320 protein expression, alone or simultaneously, which inhibits the growth of a number of cancer cells compared to non-cancer (normal) cells. In some cases, CD320 or LRP2 protein knockdown alone is sufficient to severely inhibit cancer cell proliferation compared to normal cells.

Another aspect of the invention provides for inhibiting cancer cell proliferation by inhibiting LRP2 receptor expression.

The study of the mechanism of selectivity in uptake of porphyrins by cancer cells has led to a variety of non-obvious compounds and methods of using the compounds. It was found that the knockdown of the expression of CD320 gene or LRP2 gene or the simultaneous knockdown of the expression of CD320 gene and LRP2 gene resulted in inhibition of cell death or cell growth in a panel of lung cancer cell lines, as compared to normal fibroblasts. An experimental overview is shown in figure 1. In these experiments, cells were plated on day 0. The next day (day 1), viral particles encoding short hairpin RNAs (shRNA) or unrelated shRNA controls against CD320 gene and LRP2 gene were added to the cell culture along with proteoglycan sulfate, an agent that promotes entry of the viral particles into the cells.

Further studies showed that knockdown of expression of CD320 gene or LRP2 gene or simultaneous knockdown of expression of CD320 and LRP2 genes resulted in cell death or inhibition of cell growth in a panel of cancer cell lines including lung cancer, prostate cancer, breast cancer, glioblastoma and melanoma when compared to normal fibroblasts using small interfering RNAs (siRNA) (fig. 9-10). It was also found that in some cancer cell lines, knockdown of one gene (CD 320 or LRP 2) resulted in increased expression of the other gene.

One aspect of the invention provides for the knockdown of CD320 receptor, LRP2 receptor or both CD320 receptor and LRP2 receptor in cancer cells in vivo and in vitro that express CD320 mRNA and/or LRP2 mRNA.

Another aspect of the invention is a method for inhibiting cell growth or causing cell death in a cancer cell treated with a compound described herein while leaving normal cells unaffected or allowing inhibition of cell growth or less cell death to occur to a lesser extent than a cancer cell treated with the same amount of the compound.

Another aspect of the first compounds and methods of use is selective therapy that inhibits proliferation of cancer cells and/or kills cancer cells by inhibiting LRP2 receptors while leaving normal cells intact.

Another aspect of the second compounds and methods of use is selective therapy that inhibits proliferation of cancer cells and/or kills cancer cells by inhibiting CD320 receptor while leaving normal cells intact.

Another aspect of the invention provides a method for treating cancer by administering a treatment to selectively inhibit proliferation of and/or kill cancer cells by one or more of: a first compound that is an inhibitor of the CD320 receptor, a second compound that is an inhibitor of the LRP2 receptor, or a combination thereof.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate one or more embodiments of the invention and together with the description, serve to explain the principles of the invention. The drawings are only for the purpose of illustrating one or more embodiments of the invention and are not to be construed as limiting the invention. In the drawings:

Figure 1 illustrates the experimental design for knockdown of CD320 and LRP2 in cells. Cells were plated on day 0. The next day (day 1), viral particles encoding short hairpin RNAs (shRNA) or non-targeted shRNA controls against CD320 and LRP2 mRNA were added to the cell culture along with proteoglycan sulfate, an agent that promotes entry of the viral particles into the cells. The sequences used are shown in table 1. Each shRNA coding sequence is also combined with a unique drug resistance gene, which will allow selection of those cells that ingest shRNA; cells that do not ingest shRNA will not survive. Drug selection was initiated on day 2. On day 3, cells were harvested and plated in new dishes. Only cells with the drug resistance gene, i.e., those that ingest shRNA viral particles, will survive this plating procedure. From day 4, the cell growth of each culture was closely observed. Cells infected with non-targeted negative control shRNA continued to grow-data not shown. The results for cell lines expressing cd320+lrp2shrna are shown in table 1.

Figures 2A-2C illustrate the sensitivity of cancer cell lines to CD320 and LRP2 knockdown. Normal cells (GM 05659 fibroblasts) or cancer cells were infected with lentiviruses expressing shRNA to control sequences or shCDs 320 and shLRP2, as described in FIG. 1. Cells were grown as described in fig. 1. On the ninth day after transfection with lentivirus, photographs of the cells were taken. Filled ovals represent healthy growth of normal fibroblasts infected with shRNA against CD320 and LRP 2. The dashed oval represents unhealthy dead cancer cells infected with shRNA targeting CD320 and LRP2 (fig. 2A). The cell fields in fig. 2A are counted and quantified and illustrated in fig. 2B. The data in fig. 2B were normalized to the number of control cells and are illustrated in fig. 2C. Fig. 2C shows that cultures of cells infected with lentiviruses encoding shRNA for CD320 and LRP2 (white bars) contained far fewer cells than cultures of cells exposed to shRNA control (black bars).

FIGS. 3A-3F illustrate graphs of protein levels produced by transfecting HEK293, MDA-MB-435S and MDA-MB-231 cells with siRNA against LRP2 and CD 320. HEK293, MDA-MB-435S and MDA-MB-231 cells were transfected with siRNA indicated at 20nM and incubated for 48 hours. The sirnas targeting CD320 were named OSC17 and OSC47. Sirnas targeting LRP2 were named OSL245, OSL47, OSL104, OSL90 and OSL119. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. FIGS. 3A-3F show fold changes in protein levels compared to siScramble (OSS 1 or OSS 2). (mean +/-SEM, n=3 is shown).

FIGS. 4A-4F illustrate graphs of cells after transfection of LnCAP, MCF-7 and U251 cells with siRNA against LRP2 and CD 320. LnCAP, MCF-7 and U251 cells were transfected with 20nM of indicated siRNA and incubated for 48 hours. The sirnas targeting CD320 were named OSC17 and OSC47. Sirnas targeting LRP2 were named OSL245, OSL47, OSL104, OSL90 and OSL119. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. FIGS. 4A-4F show fold changes in protein levels compared to siScramble (OSS 2).

FIGS. 5A-5C illustrate graphs of protein levels after transfection of A172, DU145 and GM05659 cells with siRNA against LRP2 and CD 320. A172, DU145 and GM05659 cells were transfected with siRNA indicated at 20nM and incubated for 48 hours. The sirnas targeting CD320 were named OSC17 and OSC47. Sirnas targeting LRP2 were named OSL245, OSL47, OSL104, OSL90 and OSL119. Whole cell lysates were prepared and immunoblotted against CD 320. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. FIGS. 5A-5C show fold changes in protein levels compared to siScramble (OSS 2).

Figure 6 illustrates a graph of relative LRP2 protein expression in various cell lines-lysates were prepared from cell lines indicated on the x-axis and western blots were performed to determine LRP2 protein levels. Results represent the mean +/-SEM of three independent lysates.

Figures 7A-7B illustrate graphs of the effect of doxorubicin treatment on cell viability as measured by CTG assay. A172 and HCC15 cells were plated in 96-well plates at 1200 cells/well. The next day, cells were treated with doxorubicin at indicated concentrations. The viability of the cells was determined 4 days after the onset of doxorubicin treatment using CTG assay. The dashed line indicates a non-linear fit to the data to calculate the IC ₅₀ value.

Fig. 8 is a schematic overview of a functional assay for screening the effect of siRNA on cell proliferation to facilitate quantification of the effect of knockdown CD320 and LRP2 on cell proliferation. Cells were seeded in 24-well plates. The following day, cells were transfected with either siRNA targeting CD320 (OSC 17, OSC 47) and/or LRP2 (OSL 231, OSL 245) or control siRNA (OSS 2). Cell lines may require repeated transfection and/or time for effective toxicity (cell line dependence). In this experimental setup, if some cell lines require re-infection for effective toxicity, there is room for re-infection. In addition, cells were treated with doxorubicin alone in a small subset of wells as a positive control for toxicity. At the end of the study, cell growth of the cell lines was analyzed by CTG assay.

Figures 9A-9E illustrate graphs of percent cell survival of siCD320 and siLRP2 versus cell proliferation-cell lines representing a variety of cancers (lung, brain) or normal fibroblasts were transfected with siRNA targeting CD320 (OSC 17, OSC 47) or LRP2 (OSL 231, OSL 245), alone or in combination (20 nM or in combination (10 nM each), respectively), or negative control siRNA (OSS 2) (20 nM), as indicated. As summarized in table 9, cells were transfected repeatedly for potent toxicity and viability was then determined by CTG assay. In our assay, doxorubicin-treated cells served as positive controls for cytotoxicity (table 8).

FIGS. 10A-10E illustrate graphs of the effect of siCD320 and siLRP2 on cell proliferation-as indicated, cell lines representing multiple types of cancer (breast, prostate, skin) were transfected with single or combination of siRNA targeting CD320 (OSC 17, OSC 47) or LRP2 (OSL 231, OSL 245). Cells were transfected repeatedly for potent toxicity and then cell viability was determined by CTG assay as summarized in table 9. In our assay, doxorubicin-treated cells served as positive controls for cytotoxicity (table 8).

Fig. 11A-11B illustrate the effect of siCD and siLRP2 molar ratios on cell proliferation, where the molar ratios of CD 320-targeting siRNA and LRP 2-targeting siRNA are different. As indicated, cell lines representing both types of cancer (breast cancer, prostate cancer) were transfected with different proportions of siRNA targeting CD320 (OSC 17) or LRP2 (OSL 245) (0-20 nM) or negative control siRNA (OSS 2). Cells were transfected repeatedly for potent toxicity and then cell viability was determined by CTG assay. In our assay, doxorubicin-treated cells served as positive controls for cytotoxicity (table 8).

FIGS. 12A-12B illustrate graphs of the duration of knockdown effects of siCD and siLRP2 on MDA-MD-231 cells. Representative cancer cell lines (MDA-MD-231) were transfected with 20nM CD320 targeted siRNA (OSC 17) or LRP2 targeted siRNA (OSL 245) or negative control siRNA (OSS 2) on day 0 and the percentage of protein knockdown was analyzed by western blot daily over a period of five days. Protein levels were normalized to negative control (OSS 2).

FIG. 13 is a schematic representation of Polyethylenimine (PEI) and siRNA complexation. PEI and siRNA were mixed together. Subsequently, a multi-complex (broadly, a nanoparticle) of PEI-siRNA complexes is formed, which is capable of entering the cell.

FIG. 14 is a schematic diagram illustrating that siRNA is a short RNA duplex, typically 16 to 30 nucleotides; the guide sequence of the siRNA is complementary to mRNA expressed in the cell. Exogenous siRNA duplex is introduced into cells by transfection methods. The siRNA duplex is separated by RISC/AGO (RNA-induced silencing complex) complex, whereby the guide strand of the siRNA hybridizes to the mRNA molecule to which it is complementary. mRNA is degraded by RISC/AGO complex with RNase activity, resulting in mRNA degradation without the production of protein encoded by mRNA. This results in a "knockdown" effect or reduced protein levels of the gene targeted by the siRNA compared to control treated cells.

FIGS. 15A-15B illustrate graphs of A172 cell line or MDA-MD-435S cell line treated with control siRNA (OSS 1, OSS 2) and siRNA against CD320mRNA (OSC 17, OSC 47) and siRNA against LRP2 mRNA (OSL 231, OSL 245) for determining the effectiveness of INTERFERIN as polyetheramine transfection reagents in delivering siRNA to cancer cells.

Fig. 16A-16D illustrate plated cells showing the effect of siCD and siLRP2 on four cell lines. As indicated, cell lines representing four types of cancers (breast cancer, two prostate cancers, skin cancer) were transfected with siRNA targeting CD320 (OSC 17) or LRP2 (OSL 245), alone or in combination (10 nM each) at 20nM, or negative control siRNA (OSS 2) (20 nM). Cells were transfected repeatedly for potent toxicity as shown in table 9, and then analyzed by microscopy as shown.

FIG. 17 illustrates a graphical depiction of CD320 mRNA. UTR refers to untranslated region, CDS refers to protein coding sequence.

Figure 18 illustrates a graphical depiction of LRP2 mRNA, UTR reference untranslated region, CDS reference protein coding sequence.

FIGS. 19A-19G illustrate the structure of non-natural nucleotides that can be incorporated within the sequence of RNAi. "B" means a natural (G, C, A, U) RNA nucleobase, a DNA nucleobase or a non-natural nucleobase. Figure 19A shows some chemical modifications to the ribose 2' -position and phosphate moiety. FIGS. 19B-19D illustrate backbone modifications to ribose moieties containing bridging groups. FIG. 19E shows the deletion of the C2'-C3' bond. FIGS. 19F-19G show additional backbone modifications to the ribose moiety wherein a six membered ring replaces a five membered ring.

Fig. 20 illustrates a schematic of an in vivo murine xenograft model for breast cancer. MDA-MB-231 cells were implanted into the flank of NSG mice and grown to a volume of 70mm ³, after which siRNAs targeting CD320 (OSC 17) and LRP2 (OSL 245) were intratumorally injected every four days.

Detailed Description

One or more embodiments of the invention provide methods and RNAi compounds for modulating expression of CD320 gene and/or LRP2 gene in a cell. In certain embodiments, CD320 and/or LRP2 specific RNAi is used to reduce or inhibit expression of CD320 gene and/or LRP2 gene. Such inhibition may be used to treat a condition such as cancer, and/or to create cell lines that may be used to screen for drugs to treat cancer.

The invention also relates to a method for knocking down (partially or completely) a targeted gene.

One embodiment of a method for producing knockdown cells and organisms comprises: introducing into a cell or organism in which a gene to be knocked down, referred to as a targeted gene, an siRNA of about 16 to about 30 nucleotides (nt), which targets the gene, and maintaining the resulting cell or organism under conditions where RNAi occurs, results in the degradation of mRNA of the targeted gene, thereby producing a knocked down cell or organism. Knockdown cells and organisms produced by the present methods are also subjects of embodiments of the invention.

One embodiment of the invention also relates to a method of examining or assessing the function of a gene in a cell or organism. In one embodiment, about 16 to about 30nt of RNA targeted to the mRNA of the gene for degradation is introduced into the cell or organism in which RNAi occurs. The cell or organism is referred to as a test cell or organism. The cell or organism is referred to as a test cell organism. The test cell or organism is maintained under conditions where the mRNA of the gene is degraded. The phenotype of the test cell or organism is then observed and compared to the phenotype of an appropriate control cell or organism, such as a corresponding cell or organism treated in the same manner except that the gene is not targeted. Instead of introducing siRNA into a test cell or organism, 16-30nt RNA that is not targeted to mRNA for degradation may be introduced into a control cell or organism, but does not have to do so. The difference between the phenotypes of the test cells and the control cells or organisms provides information about the function of the degraded mRNA.

RNA of about 16 to about 30 nucleotides is isolated or synthesized and then introduced into a cell or organism (test cell or test organism) in which RNAi occurs. The test cell or test organism is maintained under conditions where degradation of the mRNA occurs. The phenotype of the test cell or organism is then observed and compared to the phenotype of an appropriate control, such as a corresponding cell or organism treated in the same manner as the test cell or organism except that the targeted gene is not targeted. The difference between the phenotype of the test cell and the control cell or organism provides information about the function of the targeted gene. The information provided may be sufficient to identify (define) the function of the gene or may be used in combination with information obtained from other assays or analyses for this purpose.

One embodiment of the invention also includes a method of treating a disease or condition associated with the presence of a protein in an individual comprising administering to the individual about 16 to about 30 nucleotides of RNA that targets the mRNA of the protein (the mRNA encoding the protein) for degradation. Thus, the protein is not produced or not produced to the extent that it would be without treatment.

FIG. 14 shows that siRNA is a short RNA duplex, typically 16 to 30 nucleotides; the sequence of the siRNA is complementary to mRNA expressed in the cell. Exogenous siRNA duplex is introduced into cells by transfection methods. The siRNA duplex is unwound by RNA-induced silencing complex (RISC), whereby the guide strand of the siRNA hybridizes to the mRNA molecule to which it is complementary. mRNA is degraded by RISC/AGO complex which has RNase cleavage activity. The end result is that the mRNA targeted by the siRNA is degraded without producing the protein encoded by the mRNA. This results in a "knockdown" effect or reduced protein levels of the gene targeted by the siRNA compared to control treated cells.

In one embodiment, at least one strand of the RNA molecule has a 3' overhang of about 1 to about 6 nucleotides in length (e.g., pyrimidine nucleotides, purine nucleotides). In other embodiments, the 3' overhang is about 1 to about 5 nucleotides, about 1 to about 3 nucleotides, and about 2 to about 4 nucleotides, or for example, if the guide strand is a 27 mer (27-mer), the overhang may be up to 14 nucleotides. In one embodiment, the RNA molecule is double-stranded, one strand having a 3' overhang, the other strand may be blunt-ended or have an overhang. In embodiments in which the RNA molecule is double-stranded and both strands comprise overhangs, the length of the overhangs may be the same or different for each strand. In a particular embodiment, the RNA of the invention comprises a 21-27 nucleotide strand that is Watson-Crick paired and has about 1 to about 3, in particular about 2 nucleotide overhangs on both 3' ends of the RNA. To further enhance the stability of the RNA of the present invention, the 3' overhang may be stabilized against degradation. In one embodiment, the RNA is stabilized by including purine nucleotides, such as adenosine or guanosine nucleotides. Alternatively, substitution of pyrimidine nucleotides with non-natural nucleotides, such as uridine 2 nucleotide 3 'overhang with 2' -deoxythymidine, is acceptable and does not affect the efficiency of RNAi. Deletion of the 2' hydroxyl group significantly enhances nuclease resistance of overhangs in tissue culture media. The 3' -overhang may be further stabilized by introducing phosphorothioate groups instead of phosphodiester.

The 16-30nt RNA molecules of the invention can be obtained using a variety of techniques known to those skilled in the art. For example, the RNA may be chemically synthesized or recombinantly produced using methods known in the art.

For easier understanding of the present invention, certain terms are first defined. Furthermore, it should be noted that whenever a value or range of values of a parameter is recited, values and ranges intermediate to the recited values are also intended to be part of the present invention.

The articles "a" and "an" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. For example, "an element" means one element or more than one element, such as a plurality of elements.

The term "including" as used herein means, and is used interchangeably with, the phrase "including but not limited to".

The term "or" is meant herein to mean the term "and/or" and is used interchangeably with the term "and/or" unless the context clearly indicates otherwise.

As used herein, "CD320" refers to a gene or protein. CD320 is also known as the 8D6 antigen, CD320 antigen, 8D6A, the transcobalamin receptor, FDC-SM-8D6, FDC signaling molecule 8D6, TCBLR, TCblR, TCN R. The term CD320 includes: human CD320, the amino acid and nucleotide sequences of which can be found, for example, in GenBank accession nos. nm_016579.4 and nm_ 001165895.2; mouse CD320, the amino acid and nucleotide sequences of which can be found, for example, in GenBank accession No. nm_ 019421.3; rat CD320, the amino acid and nucleotide sequence of which can be found, for example, in GenBank accession No. nm_ 001014201.1. Additional examples of CD320 mRNA sequences are readily available using, for example, genBank. Additional information can be found in fig. 17.

The CD320 DNA sequence from homo sapiens is as follows: NM-016579.4 Chinesian CD320 molecule (CD 320), transcriptional variant 1, DNA

GTGCGCGTGCGCAGGGATAAGAGAGCGGTCTGGACAGCGCGTGGCCGGCGCCGCTGTGGGGACAGCATGA

GCGGCGGTTGGATGGCGCAGGTTGGAGCGTGGCGAACAGGGGCTCTGGGCCTGGCGCTGCTGCTGCTGCT

CGGCCTCGGACTAGGCCTGGAGGCCGCCGCGAGCCCGCTTTCCACCCCGACCTCTGCCCAGGCCGCAGGC

CCCAGCTCAGGCTCGTGCCCACCCACCAAGTTCCAGTGCCGCACCAGTGGCTTATGCGTGCCCCTCACCT

GGCGCTGCGACAGGGACTTGGACTGCAGCGATGGCAGCGATGAGGAGGAGTGCAGGATTGAGCCATGTAC

CCAGAAAGGGCAATGCCCACCGCCCCCTGGCCTCCCCTGCCCCTGCACCGGCGTCAGTGACTGCTCTGGG

GGAACTGACAAGAAACTGCGCAACTGCAGCCGCCTGGCCTGCCTAGCAGGCGAGCTCCGTTGCACGCTGA

GCGATGACTGCATTCCACTCACGTGGCGCTGCGACGGCCACCCAGACTGTCCCGACTCCAGCGACGAGCT

CGGCTGTGGAACCAATGAGATCCTCCCGGAAGGGGATGCCACAACCATGGGGCCCCCTGTGACCCTGGAG

AGTGTCACCTCTCTCAGGAATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCCCCTCTGTCG

GGAATGCCACATCCTCCTCTGCCGGAGACCAGTCTGGAAGCCCAACTGCCTATGGGGTTATTGCAGCTGC

TGCGGTGCTCAGTGCAAGCCTGGTCACCGCCACCCTCCTCCTTTTGTCCTGGCTCCGAGCCCAGGAGCGC

CTCCGCCCACTGGGGTTACTGGTGGCCATGAAGGAGTCCCTGCTGCTGTCAGAACAGAAGACCTCGCTGC

CCTGAGGACAAGCACTTGCCACCACCGTCACTCAGCCCTGGGCGTAGCCGGACAGGAGGAGAGCAGTGAT

GCGGATGGGTACCCGGGCACACCAGCCCTCAGAGACCTGAGCTCTTCTGGCCACGTGGAACCTCGAACCC

GAGCTCCTGCAGAAGTGGCCCTGGAGATTGAGGGTCCCTGGACACTCCCTATGGAGATCCGGGGAGCTAG

GATGGGGAACCTGCCACAGCCAGAACTGAGGGGCTGGCCCCAGGCAGCTCCCAGGGGGTAGAACGGCCCT

GTGCTTAAGACACTCCTGCTGCCCCGTCTGAGGGTGGCGATTAAAGTTGCTTCACATCCTCAAAAAAAAA

AAAAAAAAAAAAAAAAAAAAAAA(SEQ ID NO.935)。

The protein sequence of CD320 derived from the above mRNA sequence is as follows: > sp|q9npf0|cd320_human CD320 antigen os=homo sapiens ox=9606 gn=cd320 pe=1sv=1

MSGGWMAQVGAWRTGALGLALLLLLGLGLGLEAAASPLSTPTSAQAAGPSSGSCPPTKFQ

CRTSGLCVPLTWRCDRDLDCSDGSDEEECRIEPCTQKGQCPPPPGLPCPCTGVSDCSGGT

DKKLRNCSRLACLAGELRCTLSDDCIPLTWRCDGHPDCPDSSDELGCGTNEILPEGDATTMGPPVTLESVTSLRNATTMGPPVTLESVPSVGNATSSSAGDQSGSPTAYGVIAAAAVLSA

SLVTATLLLLSWLRAQERLRPLGLLVAMKESLLLSEQKTSLP(SEQ ID NO.936)

The CD320 DNA sequence from homo sapiens is as follows: NM-001165895.2 Chinesian CD320 molecule (CD 320), transcriptional variant 2, DNA

GCGTGCGCGTGCGCAGGGATAAGAGAGCGGTCTGGACAGCGCGTGGCCGGCGCCGCTGTGGGGACAGCATGAGCGGCGGTTGGATGGCGCAGGTTGGAGCGTGGCGAACAGGGGCTCTGGGCCTGGCGCTGCTGCTGCTGCTCGGCCTCGGACTAGGCCTGGAGGCCGCCGCGAGCCCGCTTTCCACCCCGACCTCTGCCCAGGCCGCAGGGATTGAGCCATGTACCCAGAAAGGGCAATGCCCACCGCCCCCTGGCCTCCCCTGCCCCTGCACCGGCGTCAGTGACTGCTCTGGGGGAACTGACAAGAAACTGCGCAACTGCAGCCGCCTGGCCTGCCTAGCAGGCGAGCTCCGTTGCACGCTGAGCGATGACTGCATTCCACTCACGTGGCGCTGCGACGGCCACCCAGACTGTCCCGACTCCAGCGACGAGCTCGGCTGTGGAACCAATGAGATCCTCCCGGAAGGGGATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCACCTCTCTCAGGAATGCCACAACCATGGGGCCCCCTGTGACCCTGGAGAGTGTCCCCTCTGTCGGGAATGCCACATCCTCCTCTGCCGGAGACCAGTCTGGAAGCCCAACTGCCTATGGGGTTATTGCAGCTGCTGCGGTGCTCAGTGCAAGCCTGGTCACCGCCACCCTCCTCCTTTTGTCCTGGCTCCGAGCCCAGGAGCGCCTCCGCCCACTGGGGTTACTGGTGGCCATGAAGGAGTCCCTGCTGCTGTCAGAACAGAAGACCTCGCTGCCCTGAGGACAAGCACTTGCCACCACCGTCACTCAGCCCTGGGCGTAGCCGGACAGGAGGAGAGCAGTGATGCGGATGGGTACCCGGGCACACCAGCCCTCAGAGACCTGAGCTCTTCTGGCCACGTGGAACCTCGAACCCGAGCTCCTGCAGAAGTGGCCCTGGAGATTGAGGGTCCCTGGACACTCCCTATGGAGATCCGGGGAGCTAGGATGGGGAACCTGCCACAGCCAGAACTGAGGGGCTGGCCCCAGGCAGCTCCCAGGGGGTAGAACGGCCCTGTGCTTAAGACACTCCTGCTGCCCCGTCTGAGGGTGGCAATTAAAGTTGCTTCACATCCTC(SEQ ID NO.937)

The protein sequence of CD320 derived from the above DNA sequence is as follows: isoform of sp|q9 npf0. 2|CD320_HUMAN CD320 antigen 2os=homo sapiens ox=9606 gn=cd320

MSGGWMAQVGAWRTGALGLALLLLLGLGLGLEAAASPLSTPTSAQAAGIEPCTQKGQCPPPPGLPCPCTGVSDCSGGTDKKLRNCSRLACLAGELRCTLSDDCIPLTWRCDGHPDCPDSSDELGCGTNEILPEGDATTMGPPVTLESVTSLRNATTMGPPVTLESVPSVGNATSSSAGDQSGSPTAYGVIAAAAVLSASLVTATLLLLSWLRAQERLRPLGLLVAMKESLLLSEQKTSLP(SEQ ID NO.938)

Furthermore, as used herein, "LRP2" refers to a gene or protein. LRP2 is also known as megalin, LRP-2, glycoprotein 330, DBS, GP330, calcium sensor protein, heymann nephritis antigen homolog, low density lipoprotein receptor-related protein 2, EC 1.1.2.3, EC 3.4.21.9, LDL receptor-related protein. The term LRP2 includes human LRP2, the amino acid and nucleotide sequences of which can be found, for example, in GenBank accession No. nm_ 004525.3; mouse LRP2, the amino acid and nucleotide sequences of which can be found, for example, in GenBank accession No. nm_ 001081088.2; rat LRP2, its amino acid and nucleotide sequence can be found, for example, in GenBank accession No. nm_ 030827.1. Additional examples of LRP2 mRNA sequences are readily available using, for example, genBank. Additional information can be found in fig. 18.

One example of LRP2 is: nm_004525.3 homo sapiens LDL receptor associated protein 2 (LRP 2), DNA:

GGTCTAAAGGGCTTTATGCACTGTCTGGAGGGTGGGGACTGGCGCGGGTAGAAAACGGGATGCCTCGGGC

GTGGGGGCAGGCTTTTGGCCACTAGGAGCTGGCGGAGGTGCAGACCTAAAGGAGCGTTCGCTAGCAGAGG

CGCTGCCGGTGCGGTGTGCTACGCGCGCCCACCTCCCGGGGAAGGAACGGCGAGGCCGGGGACCGTCGCG

GAGATGGATCGCGGGCCGGCAGCAGTGGCGTGCACGCTGCTCCTGGCTCTCGTCGCCTGCCTAGCGCCGG

CCAGTGGCCAAGAATGTGACAGTGCGCATTTTCGCTGTGGAAGTGGGCATTGCATCCCTGCAGACTGGAG

GTGTGATGGGACCAAAGACTGTTCAGATGACGCGGATGAAATTGGCTGCGCTGTTGTGACCTGCCAGCAG

GGCTATTTCAAGTGCCAGAGTGAGGGACAATGCATCCCCAACTCCTGGGTGTGTGACCAAGATCAAGACT

GTGATGATGGCTCAGATGAACGTCAAGATTGCTCACAAAGTACATGCTCAAGTCATCAGATAACATGCTC

CAATGGTCAGTGTATCCCAAGTGAATACAGGTGCGACCACGTCAGAGACTGCCCCGATGGAGCTGATGAG

AATGACTGCCAGTACCCAACATGTGAGCAGCTTACTTGTGACAATGGGGCCTGCTATAACACCAGTCAGA

AGTGTGATTGGAAAGTTGATTGCAGGGACTCCTCAGATGAAATCAACTGCACTGAGATATGCTTGCACAA

TGAGTTTTCATGTGGCAATGGAGAGTGTATCCCTCGTGCTTATGTCTGTGACCATGACAATGATTGCCAA

GACGGCAGTGACGAACATGCTTGCAACTATCCGACCTGCGGTGGTTACCAGTTCACTTGCCCCAGTGGCC

GATGCATTTATCAAAACTGGGTTTGTGATGGAGAAGATGACTGTAAAGATAATGGAGATGAAGATGGATG

TGAAAGCGGTCCTCATGATGTTCATAAATGTTCCCCAAGAGAATGGTCTTGCCCAGAGTCGGGACGATGC

ATCTCCATTTATAAAGTTTGTGATGGGATTTTAGATTGCCCAGGAAGAGAAGATGAAAACAACACTAGTA

CCGGAAAATACTGTAGTATGACTCTGTGCTCTGCCTTGAACTGCCAGTACCAGTGCCATGAGACGCCGTA

TGGAGGAGCGTGTTTTTGTCCCCCAGGTTATATCATCAACCACAATGACAGCCGTACCTGTGTTGAGTTT

GATGATTGCCAGATATGGGGAATTTGTGACCAGAAGTGTGAAAGCCGACCTGGCCGTCACCTGTGCCACT

GTGAAGAAGGGTATATCTTGGAGCGTGGACAGTATTGCAAAGCTAATGATTCCTTTGGCGAGGCCTCCAT

TATCTTCTCCAATGGTCGGGATTTGTTAATTGGTGATATTCATGGAAGGAGCTTCCGGATCCTAGTGGAG

TCTCAGAATCGTGGAGTGGCCGTGGGTGTGGCTTTCCACTATCACCTGCAAAGAGTTTTTTGGACAGACA

CCGTGCAAAATAAGGTTTTTTCAGTTGACATTAATGGTTTAAATATCCAAGAGGTTCTCAATGTTTCTGT

TGAAACCCCAGAGAACCTGGCTGTGGACTGGGTTAATAATAAAATCTATCTAGTGGAAACCAAGGTCAAC

CGCATAGATATGGTAAATTTGGATGGAAGCTATCGGGTTACCCTTATAACTGAAAACTTGGGGCATCCTA

GAGGAATTGCCGTGGACCCAACTGTTGGTTATTTATTTTTCTCAGATTGGGAGAGCCTTTCTGGGGAACC

TAAGCTGGAAAGGGCATTCATGGATGGCAGCAACCGTAAAGACTTGGTGAAAACAAAGCTGGGATGGCCT

GCTGGGGTAACTCTGGATATGATATCGAAGCGTGTTTACTGGGTTGACTCTCGGTTTGATTACATTGAAA

CTGTAACTTATGATGGAATTCAAAGGAAGACTGTAGTTCATGGAGGCTCCCTCATTCCTCATCCCTTTGG

AGTAAGCTTATTTGAAGGTCAGGTGTTCTTTACAGATTGGACAAAGATGGCCGTGCTGAAGGCAAACAAG

TTCACAGAGACCAACCCACAAGTGTACTACCAGGCTTCCCTGAGGCCCTATGGAGTGACTGTTTACCATT

CCCTCAGACAGCCCTATGCTACCAATCCGTGTAAAGATAACAATGGGGGCTGTGAGCAGGTCTGTGTCCT

CAGCCACAGAACAGATAATGATGGTTTGGGTTTCCGTTGCAAGTGCACATTCGGCTTCCAACTGGATACA

GATGAGCGCCACTGCATTGCTGTTCAGAATTTCCTCATTTTTTCATCCCAAGTTGCTATTCGTGGGATCC

CGTTCACCTTGTCTACCCAGGAAGATGTCATGGTTCCAGTTTCGGGGAATCCTTCTTTCTTTGTCGGGAT

TGATTTTGACGCCCAGGACAGCACTATCTTTTTTTCAGATATGTCAAAACACATGATTTTTAAGCAAAAG

ATTGATGGCACAGGAAGAGAAATTCTCGCAGCTAACAGGGTGGAAAATGTTGAAAGTTTGGCTTTTGATT

GGATTTCAAAGAATCTCTATTGGACAGACTCTCATTACAAGAGTATCAGTGTCATGAGGCTAGCTGATAA

AACGAGACGCACAGTAGTTCAGTATTTAAATAACCCACGGTCGGTGGTAGTTCATCCTTTTGCCGGGTAT

CTATTCTTCACTGATTGGTTCCGTCCTGCTAAAATTATGAGAGCATGGAGTGACGGATCTCACCTCTTGC

CTGTAATAAACACTACTCTTGGATGGCCCAATGGCTTGGCCATCGATTGGGCTGCTTCACGATTGTACTG

GGTAGATGCCTATTTTGATAAAATTGAGCACAGCACCTTTGATGGTTTAGACAGAAGAAGACTGGGCCAT

ATAGAGCAGATGACACATCCGTTTGGACTTGCCATCTTTGGAGAGCATTTATTTTTTACTGACTGGAGAC

TGGGTGCCATTATTCGAGTCAGGAAAGCAGATGGTGGAGAAATGACAGTTATCCGAAGTGGCATTGCTTA

CATACTGCATTTGAAATCGTATGATGTCAACATCCAGACTGGTTCTAACGCCTGTAATCAACCCACGCAT

CCTAACGGTGACTGCAGCCACTTCTGCTTCCCGGTGCCAAATTTCCAGCGAGTGTGTGGGTGCCCTTATG

GAATGAGGCTGGCTTCCAATCACTTGACATGCGAGGGGGACCCAACCAATGAACCACCCACAGAGCAGTG

TGGCTTATTTTCCTTCCCCTGTAAAAATGGCAGATGTGTGCCCAATTACTATCTCTGTGATGGAGTCGAT

GATTGTCATGATAACAGTGATGAGCAACTATGTGGCACACTTAATAATACCTGTTCATCTTCGGCGTTCA

CCTGTGGCCATGGGGAGTGCATTCCTGCACACTGGCGCTGTGACAAACGCAACGACTGTGTGGATGGCAG

TGATGAGCACAACTGCCCCACCCACGCACCTGCTTCCTGCCTTGACACCCAATACACCTGTGATAATCAC

CAGTGTATCTCAAAGAACTGGGTCTGTGACACAGACAATGATTGTGGGGATGGATCTGATGAAAAGAACT

GCAATTCGACAGAGACATGCCAACCTAGTCAGTTTAATTGCCCCAATCATCGATGTATTGACCTATCGTT

TGTCTGTGATGGTGACAAGGATTGTGTTGATGGATCTGATGAGGTTGGTTGTGTATTAAACTGTACTGCT

TCTCAATTCAAGTGTGCCAGTGGGGATAAATGTATTGGCGTCACAAATCGTTGTGATGGTGTTTTTGATT

GCAGTGACAACTCGGATGAAGCAGGCTGTCCAACCAGGCCTCCTGGTATGTGCCACTCAGATGAATTTCA

GTGCCAAGAAGATGGTATCTGCATCCCGAACTTCTGGGAATGTGATGGGCATCCAGACTGCCTCTATGGA

TCTGATGAGCACAATGCCTGTGTCCCCAAGACTTGCCCTTCATCATATTTCCACTGTGACAACGGAAACT

GCATCCACAGGGCATGGCTCTGTGATCGGGACAATGACTGCGGGGATATGAGTGATGAGAAGGACTGCCC

TACTCAGCCCTTTCGCTGTCCTAGTTGGCAATGGCAGTGTCTTGGCCATAACATCTGTGTGAATCTGAGT

GTAGTGTGTGATGGCATCTTTGACTGCCCCAATGGGACAGATGAGTCCCCACTTTGCAATGGGAACAGCT

GCTCAGATTTCAATGGTGGTTGTACTCACGAGTGTGTTCAAGAGCCCTTTGGGGCTAAATGCCTATGTCC

ATTGGGATTCTTACTTGCCAATGATTCTAAGACCTGTGAAGACATAGATGAATGTGATATTCTAGGCTCT

TGTAGCCAGCACTGTTACAATATGAGAGGTTCTTTCCGGTGCTCGTGTGATACAGGCTACATGTTAGAAA

GTGATGGGAGGACTTGCAAAGTTACAGCATCTGAGAGTCTGCTGTTACTTGTGGCAAGTCAGAACAAAAT

TATTGCCGACAGTGTCACCTCCCAGGTCCACAATATCTATTCATTGGTCGAGAATGGTTCTTACATTGTA

GCTGTTGATTTTGATTCAATTAGTGGTCGTATCTTTTGGTCTGATGCAACTCAGGGTAAAACCTGGAGTG

CGTTTCAAAATGGAACGGACAGAAGAGTGGTATTTGACAGTAGCATCATCTTGACTGAAACTATTGCAAT

AGATTGGGTAGGTCGTAATCTTTACTGGACAGACTATGCTCTGGAAACAATTGAAGTCTCCAAAATTGAT

GGGAGCCACAGGACTGTGCTGATTAGTAAAAACCTAACAAATCCAAGAGGACTAGCATTAGATCCCAGAA

TGAATGAGCATCTACTGTTCTGGTCTGACTGGGGCCACCACCCTCGCATCGAGCGAGCCAGCATGGACGG

CAGCATGCGCACTGTCATTGTCCAGGACAAGATCTTCTGGCCCTGCGGCTTAACTATTGACTACCCCAAC

AGACTGCTCTACTTCATGGACTCCTATCTTGATTACATGGACTTTTGTGATTATAATGGACACCATCGGA

GACAGGTGATAGCCAGTGATTTGATTATACGGCACCCCTATGCCCTAACTCTCTTTGAAGACTCTGTGTA

CTGGACTGACCGTGCTACTCGTCGGGTTATGCGAGCCAACAAGTGGCATGGAGGGAACCAGTCAGTTGTA

ATGTATAATATTCAATGGCCCCTTGGGATTGTTGCGGTTCATCCTTCGAAACAACCAAATTCCGTGAATC

CATGTGCCTTTTCCCGCTGCAGCCATCTCTGCCTGCTTTCCTCACAGGGGCCTCATTTTTACTCCTGTGT

TTGTCCTTCAGGATGGAGTCTGTCTCCTGATCTCCTGAATTGCTTGAGAGATGATCAACCTTTCTTAATA

ACTGTAAGGCAACATATAATTTTTGGAATCTCCCTTAATCCTGAGGTGAAGAGCAATGATGCTATGGTCC

CCATAGCAGGGATACAGAATGGTTTAGATGTTGAATTTGATGATGCTGAGCAATACATCTATTGGGTTGA

AAATCCAGGTGAAATTCACAGAGTGAAGACAGATGGCACCAACAGGACAGTATTTGCTTCTATATCTATG

GTGGGGCCTTCTATGAACCTGGCCTTAGATTGGATTTCAAGAAACCTTTATTCTACCAATCCTAGAACTC

AGTCAATCGAGGTTTTGACACTCCACGGAGATATCAGATACAGAAAAACATTGATTGCCAATGATGGGAC

AGCTCTTGGAGTTGGCTTTCCAATTGGCATAACTGTTGATCCTGCTCGTGGGAAGCTGTACTGGTCAGAC

CAAGGAACTGACAGTGGGGTTCCTGCCAAGATCGCCAGTGCTAACATGGATGGCACATCTGTGAAAACTC

TCTTTACTGGGAACCTCGAACACCTGGAGTGTGTCACTCTTGACATCGAAGAGCAGAAACTCTACTGGGC

AGTCACTGGAAGAGGAGTGATTGAAAGAGGAAACGTGGATGGAACAGATCGAATGATCCTGGTACACCAG

CTTTCCCACCCCTGGGGAATTGCAGTCCATGATTCTTTCCTTTATTATACTGATGAACAGTATGAGGTCA

TTGAAAGAGTTGATAAGGCCACTGGGGCCAACAAAATAGTCTTGAGAGATAATGTTCCAAATCTGAGGGG

TCTTCAAGTTTATCACAGACGCAATGCCGCCGAATCCTCAAATGGCTGTAGCAACAACATGAATGCCTGT

CAGCAGATTTGCCTGCCTGTACCAGGAGGATTGTTTTCCTGCGCCTGTGCCACTGGATTTAAACTCAATC

CTGATAATCGGTCCTGCTCTCCATATAACTCTTTCATTGTTGTTTCAATGCTGTCTGCAATCAGAGGCTT

TAGCTTGGAATTGTCAGATCATTCAGAAACCATGGTGCCGGTGGCAGGCCAAGGACGAAACGCACTGCAT

GTGGATGTGGATGTGTCCTCTGGCTTTATTTATTGGTGTGATTTTAGCAGCTCAGTGGCATCTGATAATG

CGATCCGTAGAATTAAACCAGATGGATCTTCTCTGATGAACATTGTGACACATGGAATAGGAGAAAATGG

AGTCCGGGGTATTGCAGTGGATTGGGTAGCAGGAAATCTTTATTTCACCAATGCCTTTGTTTCTGAAACA

CTGATAGAAGTTCTGCGGATCAATACTACTTACCGCCGTGTTCTTCTTAAAGTCACAGTGGACATGCCTA

GGCATATTGTTGTAGATCCCAAGAACAGATACCTCTTCTGGGCTGACTATGGGCAGAGACCAAAGATTGA

GCGTTCTTTCCTTGACTGTACCAATCGAACAGTGCTTGTGTCAGAGGGCATTGTCACACCACGGGGCTTG

GCAGTGGACCGAAGTGATGGCTACGTTTATTGGGTTGATGATTCTTTAGATATAATTGCAAGGATTCGTA

TCAATGGAGAGAACTCTGAAGTGATTCGTTATGGCAGTCGTTACCCAACTCCTTATGGCATCACTGTTTT

TGAAAATTCTATCATATGGGTAGATAGGAATTTGAAAAAGATCTTCCAAGCCAGCAAGGAACCAGAGAAC

ACAGAGCCACCCACAGTGATAAGAGACAATATCAACTGGCTAAGAGATGTGACCATCTTTGACAAGCAAG

TCCAGCCCCGGTCACCAGCAGAGGTCAACAACAACCCTTGCTTGGAAAACAATGGTGGGTGCTCTCATCT

CTGCTTTGCTCTGCCTGGATTGCACACCCCAAAATGTGACTGTGCCTTTGGGACCCTGCAAAGTGATGGC

AAGAATTGTGCCATTTCAACAGAAAATTTCCTCATCTTTGCCTTGTCTAATTCCTTGAGAAGCTTACACT

TGGACCCTGAAAACCATAGCCCACCTTTCCAAACAATAAATGTGGAAAGAACTGTCATGTCTCTAGACTA

TGACAGTGTAAGTGATAGAATCTACTTCACACAAAATTTAGCCTCTGGAGTTGGACAGATTTCCTATGCC

ACCCTGTCTTCAGGGATCCATACTCCAACTGTCATTGCTTCAGGTATAGGGACTGCTGATGGCATTGCCT

TTGACTGGATTACTAGAAGAATTTATTACAGTGACTACCTCAACCAGATGATTAATTCCATGGCTGAAGA

TGGGTCTAACCGCACTGTGATAGCCCGCGTTCCAAAACCAAGAGCAATTGTGTTAGATCCCTGCCAAGGG

TACCTGTACTGGGCTGACTGGGATACACATGCCAAAATCGAGAGAGCCACATTGGGAGGAAACTTCCGCG

TACCCATTGTGAACAGCAGTCTGGTCATGCCCAGTGGGCTGACTCTGGACTATGAAGAGGACCTTCTCTA

CTGGGTGGATGCTAGTCTGCAGAGGATTGAACGCAGCACTCTGACGGGCGTGGATCGTGAAGTCATTGTC

AATGCAGCCGTTCATGCTTTTGGCTTGACTCTCTATGGCCAGTATATTTACTGGACTGACTTGTACACAC

AAAGAATTTACCGAGCTAACAAATATGACGGGTCAGGTCAGATTGCAATGACCACAAATTTGCTCTCCCA

GCCCAGGGGAATCAACACTGTTGTGAAGAACCAGAAACAACAGTGTAACAATCCTTGTGAACAGTTTAAT

GGGGGCTGCAGCCATATCTGTGCACCAGGTCCAAATGGTGCCGAGTGCCAGTGTCCACATGAGGGCAACT

GGTATTTGGCCAACAACAGGAAGCACTGCATTGTGGACAATGGTGAACGATGTGGTGCATCTTCCTTCAC

CTGCTCCAATGGGCGCTGCATCTCGGAAGAGTGGAAGTGTGATAATGACAACGACTGTGGGGATGGCAGT

GATGAGATGGAAAGTGTCTGTGCACTTCACACCTGCTCACCGACAGCCTTCACCTGTGCCAATGGGCGAT

GTGTCCAATACTCTTACCGCTGTGATTACTACAATGACTGTGGTGATGGCAGTGATGAGGCAGGGTGCCT

GTTCAGGGACTGCAATGCCACCACGGAGTTTATGTGCAATAACAGAAGGTGCATACCTCGTGAGTTTATC

TGCAATGGTGTAGACAACTGCCATGATAATAACACTTCAGATGAGAAAAATTGCCCTGATCGCACTTGCC

AGTCTGGATACACAAAATGTCATAATTCAAATATTTGTATTCCTCGCGTTTATTTGTGTGACGGAGACAA

TGACTGTGGAGATAACAGTGATGAAAACCCTACTTATTGCACCACTCACACGTGCAGCAGCAGTGAGTTC

CAATGCGCATCTGGGCGCTGTATTCCTCAACATTGGTATTGTGATCAAGAAACAGATTGTTTTGATGCCT

CTGATGAACCTGCCTCTTGTGGTCACTCTGAGCGAACATGCCTAGCTGATGAGTTCAAGTGTGATGGTGG

GAGGTGCATCCCAAGCGAATGGATCTGTGACGGTGATAATGACTGTGGGGATATGAGTGACGAGGATAAA

AGGCACCAGTGTCAGAATCAAAACTGCTCGGATTCCGAGTTTCTCTGTGTAAATGACAGACCTCCGGACA

GGAGGTGCATTCCCCAGTCTTGGGTCTGTGATGGCGATGTGGATTGTACTGACGGCTACGATGAGAATCA

GAATTGCACCAGGAGAACTTGCTCTGAAAATGAATTCACCTGTGGTTACGGACTGTGTATCCCAAAGATA

TTCAGGTGTGACCGGCACAATGACTGTGGTGACTATAGCGACGAGAGGGGCTGCTTATACCAGACTTGCC

AACAGAATCAGTTTACCTGTCAGAACGGGCGCTGCATTAGTAAAACCTTCGTCTGTGATGAGGATAATGA

CTGTGGAGACGGATCTGATGAGCTGATGCACCTGTGCCACACCCCAGAACCCACGTGTCCACCTCACGAG

TTCAAGTGTGACAATGGGCGCTGCATCGAGATGATGAAACTCTGCAACCACCTAGATGACTGTTTGGACA

ACAGCGATGAGAAAGGCTGTGGCATTAATGAATGCCATGACCCTTCAATCAGTGGCTGCGATCACAACTG

CACAGACACCTTAACCAGTTTCTATTGTTCCTGTCGTCCTGGTTACAAGCTCATGTCTGACAAGCGGACT

TGTGTTGATATTGATGAATGCACAGAGATGCCTTTTGTCTGTAGCCAGAAGTGTGAGAATGTAATAGGCT

CCTACATCTGTAAGTGTGCCCCAGGCTACCTCCGAGAACCAGATGGAAAGACCTGCCGGCAAAACAGTAA

CATCGAACCCTATCTCATTTTTAGCAACCGTTACTATTTGAGAAATTTAACTATAGATGGCTATTTTTAC

TCCCTCATCTTGGAAGGACTGGACAATGTTGTGGCATTAGATTTTGACCGAGTAGAGAAGAGATTGTATT

GGATTGATACACAGAGGCAAGTCATTGAGAGAATGTTTCTGAATAAGACAAACAAGGAGACAATCATAAA

CCACAGACTACCAGCTGCAGAAAGTCTGGCTGTAGACTGGGTTTCCAGAAAGCTCTACTGGTTGGATGCC

CGCCTGGATGGCCTCTTTGTCTCTGACCTCAATGGTGGACACCGCCGCATGCTGGCCCAGCACTGTGTGG

ATGCCAACAACACCTTCTGCTTTGATAATCCCAGAGGACTTGCCCTTCACCCTCAATATGGGTACCTCTA

CTGGGCAGACTGGGGTCACCGCGCATACATTGGGAGAGTAGGCATGGATGGAACCAACAAGTCTGTGATA

ATCTCCACCAAGTTAGAGTGGCCTAATGGCATCACCATTGATTACACCAATGATCTACTCTACTGGGCAG

ATGCCCACCTGGGTTACATAGAGTACTCTGATTTGGAGGGCCACCATCGACACACGGTGTATGATGGGGC

ACTGCCTCACCCTTTCGCTATTACCATTTTTGAAGACACTATTTATTGGACAGATTGGAATACAAGGACA

GTGGAAAAGGGAAACAAATATGATGGATCAAATAGACAGACACTGGTGAACACAACACACAGACCATTTG

ACATCCATGTGTACCATCCATATAGGCAGCCCATTGTGAGCAATCCCTGTGGTACCAACAATGGTGGCTG

TTCTCATCTCTGCCTCATCAAGCCAGGAGGAAAAGGGTTCACTTGCGAGTGTCCAGATGACTTCCGCACC

CTTCAGCTGAGTGGCAGCACCTACTGCATGCCCATGTGCTCCAGCACCCAGTTCCTGTGCGCTAACAATG

AAAAGTGCATTCCTATCTGGTGGAAATGTGATGGACAGAAAGACTGCTCAGATGGCTCTGATGAACTGGC

CCTTTGCCCGCAGCGCTTCTGCCGACTGGGACAGTTCCAGTGCAGTGACGGCAACTGCACCAGCCCGCAG

ACTTTATGCAATGCTCACCAAAATTGCCCTGATGGGTCTGATGAAGACCGTCTTCTTTGTGAGAATCACC

ACTGTGACTCCAATGAATGGCAGTGCGCCAACAAACGTTGCATCCCAGAATCCTGGCAGTGTGACACATT

TAACGACTGTGAGGATAACTCAGATGAAGACAGTTCCCACTGTGCCAGCAGGACCTGCCGGCCGGGCCAG

TTTCGGTGTGCTAATGGCCGCTGCATCCCGCAGGCCTGGAAGTGTGATGTGGATAATGATTGTGGAGACC

ACTCGGATGAGCCCATTGAAGAATGCATGAGCTCTGCCCATCTCTGTGACAACTTCACAGAATTCAGCTG

CAAAACAAATTACCGCTGCATCCCAAAGTGGGCCGTGTGCAATGGTGTAGATGACTGCAGGGACAACAGT

GATGAGCAAGGCTGTGAGGAGAGGACATGCCATCCTGTGGGGGATTTCCGCTGTAAAAATCACCACTGCA

TCCCTCTTCGTTGGCAGTGTGATGGGCAAAATGACTGTGGAGATAACTCAGATGAGGAAAACTGTGCTCC

CCGGGAGTGCACAGAGAGCGAGTTTCGATGTGTCAATCAGCAGTGCATTCCCTCGCGATGGATCTGTGAC

CATTACAACGACTGTGGGGACAACTCAGATGAACGGGACTGTGAGATGAGGACCTGCCATCCTGAATATT

TTCAGTGTACAAGTGGACATTGTGTACACAGTGAACTGAAATGCGATGGATCCGCTGACTGTTTGGATGC

GTCTGATGAAGCTGATTGTCCCACACGCTTTCCTGATGGTGCATACTGCCAGGCTACTATGTTCGAATGC

AAAAACCATGTTTGTATCCCGCCATATTGGAAATGTGATGGCGATGATGACTGTGGCGATGGTTCAGATG

AAGAACTTCACCTGTGCTTGGATGTTCCCTGTAATTCACCAAACCGTTTCCGGTGTGACAACAATCGCTG

CATTTATAGTCATGAGGTGTGCAATGGTGTGGATGACTGTGGAGATGGAACTGATGAGACAGAGGAGCAC

TGTAGAAAACCGACCCCTAAACCTTGTACAGAATATGAATATAAGTGTGGCAATGGGCATTGCATTCCAC

ATGACAATGTGTGTGATGATGCCGATGACTGTGGTGACTGGTCCGATGAACTGGGTTGCAATAAAGGAAA

AGAAAGAACATGTGCTGAAAATATATGCGAGCAAAATTGTACCCAATTAAATGAAGGAGGATTTATCTGC

TCCTGTACAGCTGGGTTCGAAACCAATGTTTTTGACAGAACCTCCTGTCTAGATATCAATGAATGTGAAC

AATTTGGGACTTGTCCCCAGCACTGCAGAAATACCAAAGGAAGTTATGAGTGTGTCTGTGCTGATGGCTT

CACGTCTATGAGTGACCGCCCTGGAAAACGATGTGCAGCTGAGGGTAGCTCTCCTTTGTTGCTACTGCCT

GACAATGTCCGAATTCGAAAATATAATCTCTCATCTGAGAGGTTCTCAGAGTATCTTCAAGATGAGGAAT

ATATCCAAGCTGTTGATTATGATTGGGATCCCAAGGACATAGGCCTCAGTGTTGTGTATTACACTGTGCG

AGGGGAGGGCTCTAGGTTTGGTGCTATCAAACGTGCCTACATCCCCAACTTTGAATCCGGCCGCAATAAT

CTTGTGCAGGAAGTTGACCTGAAACTGAAATACGTAATGCAGCCAGATGGAATAGCAGTGGACTGGGTTG

GAAGGCATATTTACTGGTCAGATGTCAAGAATAAACGCATTGAGGTGGCTAAACTTGATGGAAGGTACAG

AAAGTGGCTGATTTCCACTGACCTGGACCAACCAGCTGCTATTGCTGTGAATCCCAAACTAGGGCTTATG

TTCTGGACTGACTGGGGAAAGGAACCTAAAATCGAGTCTGCCTGGATGAATGGAGAGGACCGCAACATCC

TGGTTTTCGAGGACCTTGGTTGGCCAACTGGCCTTTCTATCGATTATTTGAACAATGACCGAATCTACTG

GAGTGACTTCAAGGAGGACGTTATTGAAACCATAAAATATGATGGGACTGATAGGAGAGTCATTGCAAAG

GAAGCAATGAACCCTTACAGCCTGGACATCTTTGAAGACCAGTTATACTGGATATCTAAGGAAAAGGGAG

AAGTATGGAAACAAAATAAATTTGGGCAAGGAAAGAAAGAGAAAACGCTGGTAGTGAACCCTTGGCTCAC

TCAAGTTCGAATCTTTCATCAACTCAGATACAATAAGTCAGTGCCCAACCTTTGCAAACAGATCTGCAGC

CACCTCTGCCTTCTGAGACCTGGAGGATACAGCTGTGCCTGTCCCCAAGGCTCCAGCTTTATAGAGGGGA

GCACCACTGAGTGTGATGCAGCCATCGAACTGCCTATCAACCTGCCCCCCCCATGCAGGTGCATGCACGG

AGGAAATTGCTATTTTGATGAGACTGACCTCCCCAAATGCAAGTGTCCTAGCGGCTACACCGGAAAATAT

TGTGAAATGGCGTTTTCAAAAGGCATCTCTCCAGGAACAACCGCAGTAGCTGTGCTGTTGACAATCCTCT

TGATCGTCGTAATTGGAGCTCTGGCAATTGCAGGATTCTTCCACTATAGAAGGACCGGCTCCCTTTTGCC

TGCTCTGCCCAAGCTGCCAAGCTTAAGCAGTCTCGTCAAGCCCTCTGAAAATGGGAATGGGGTGACCTTC

AGATCAGGGGCAGATCTTAACATGGATATTGGAGTGTCTGGTTTTGGACCTGAGACTGCTATTGACAGGT

CAATGGCAATGAGTGAAGACTTTGTCATGGAAATGGGGAAGCAGCCCATAATATTTGAAAACCCAATGTA

CTCAGCCAGAGACAGTGCTGTCAAAGTGGTTCAGCCAATCCAGGTGACTGTATCTGAAAATGTGGATAAT

AAGAATTATGGAAGTCCCATAAACCCTTCTGAGATAGTTCCAGAGACAAACCCAACTTCACCAGCTGCTG

ATGGAACTCAGGTGACAAAATGGAATCTCTTCAAACGAAAATCTAAACAAACTACCAACTTTGAAAATCC

AATCTATGCACAGATGGAGAACGAGCAAAAGGAAAGTGTTGCTGCGACACCACCTCCATCACCTTCGCTC

CCTGCTAAGCCTAAGCCTCCTTCGAGAAGAGACCCAACTCCAACCTATTCTGCAACAGAAGACACTTTTA

AAGACACCGCAAATCTTGTTAAAGAAGACTCTGAAGTATAGCTATACCAGCTATTTAGGGAATAATTAGA

AACACACTTTTGCACATATATTTTTTACAAACAGATGAAAAAAGTTAACATTCAGTACTTTATGAAAAAA

ATATATTTTTCCCTGTTTGCCTATAGTTGGAGGTATCCTGTGTGTCTTTTTTTACTTATGCCGTCTCATA

TTTTTACAAATAATTATCACAATGTACTATATGTATATCTTTGCACTGAAGTTGTCTGAAGGTAATACTA

TAAATATATTGTATATTTGTAAATTTTGGAAAGATTATCCTGTTACTGAATTTGCTAATAAAGATGTCTG

CTGATTTGGTTGGTGATCATTATAGTAAATGATCCAACAAGAAAAGGAATTGACTGGGGACCTTTAGCCG

TGTCTAAAGAAGAGGCACCACTCATATTTCCTATAAAATTATCTAGGAAAGGAATCCAGGCCCCGCTCTT

GGGTCCATTTTTACACATTAGCACTTAATTAATGTTCAATATTACATGTCAATTTGATTAATGGCTATGT

TGATAGGGGCCACTATGTGTTGTATAGACATCTGGACTTGACTGTAGACTCCTCAGATAATACAGAAGGT

AGGAAAAGCAATTCAGTTTGGCCCTTCTGTGTGTTGGCATTGTCTAACCAGAACTCTCTGTTTCATGTGT

GTTCTCTCACTAGCTGCCAAGACAACATTTTTATTTGTGATGTCTATGAGGAAATCCCATATCATTAAGT

GCCAGTGTCCTGCATTGAGTTTGTGGTTAATTAAATGAGCTCTTCTGCTGATGGACCCTGGAGCAATTTC

TCCCCTCACCTGACATTCAAGGTGGTCACCTGCCCTAGTAGTTGGAGCTCAGTAGCTGAATTTCTGAAAC

CAAATCTGTGTCTTCATAAAATAAGGTGCAAAAAAAAAAAATACCAGTTAAGTAAAGCCTCAACTGGGTT

TTTGTTTCTATGAAAATATCATTATAATCACTATTTATTTCCTAAGTTGAACCTGAATAGAAAGGGAAAC

CATTCTTATTAAGCTTTTTATTAGGCCCTGTGGCTAAATGTGTACATTTATATTAGAATGTACTGTACAG

TCCAGATCTTTTCTTTAATTCTTATTGGTTTTTTTTTTTTTTTTTTTTTTAGAGATGGAGTCTTGCTATA

TTGCCAAGGCTGATCTTGAAGTCCTGGGCTCAAGTGATCCTCCCACCTCAGCCTCCTGAGTGGTTGGGGT

TACGGGCGTGAGCCACTGTGCCTGGCTTCCAGCTCTCCTCTTAAATAGTGGGTATAGTCTGCACAACAGG

AACCATGGCAGGAATATACACTTTCCCATAGCAAATAGCATACCTGACTCTCTGTGCTAATATTGCACAT

TTGTTAAACAATGAATGAATGGATGGATGGATGGATGGATGAATGAATGAAACATATACTACTGATTATT

TTATTCCAGAGTTCTCAAAATATTTGTTGCTGATATTTTGAGTGCTGACTGTAATTACTTTGATTAGATA

AACAACTGGAAATAATGCTGCTGAAAAAGTTCTAATAAATGTGTATTTTATCAGA(SEQ ID NO.939)。

an example of a protein sequence from the LRP2 DNA described above is: sp|p98164|lrp2_human low density lipoprotein receptor-related protein 2os=homo sapiens ox=9606 gn=lrp2pe=1sv=3

MDRGPAAVACTLLLALVACLAPASGQECDSAHFRCGSGHCIPADWRCDGTKDCSDDADEI

GCAVVTCQQGYFKCQSEGQCIPNSWVCDQDQDCDDGSDERQDCSQSTCSSHQITCSNGQC

IPSEYRCDHVRDCPDGADENDCQYPTCEQLTCDNGACYNTSQKCDWKVDCRDSSDEINCT

EICLHNEFSCGNGECIPRAYVCDHDNDCQDGSDEHACNYPTCGGYQFTCPSGRCIYQNWV

CDGEDDCKDNGDEDGCESGPHDVHKCSPREWSCPESGRCISIYKVCDGILDCPGREDENN

TSTGKYCSMTLCSALNCQYQCHETPYGGACFCPPGYIINHNDSRTCVEFDDCQIWGICDQ

KCESRPGRHLCHCEEGYILERGQYCKANDSFGEASIIFSNGRDLLIGDIHGRSFRILVES

QNRGVAVGVAFHYHLQRVFWTDTVQNKVFSVDINGLNIQEVLNVSVETPENLAVDWVNNK

IYLVETKVNRIDMVNLDGSYRVTLITENLGHPRGIAVDPTVGYLFFSDWESLSGEPKLER

AFMDGSNRKDLVKTKLGWPAGVTLDMISKRVYWVDSRFDYIETVTYDGIQRKTVVHGGSL

IPHPFGVSLFEGQVFFTDWTKMAVLKANKFTETNPQVYYQASLRPYGVTVYHSLRQPYAT

NPCKDNNGGCEQVCVLSHRTDNDGLGFRCKCTFGFQLDTDERHCIAVQNFLIFSSQVAIR

GIPFTLSTQEDVMVPVSGNPSFFVGIDFDAQDSTIFFSDMSKHMIFKQKIDGTGREILAA

NRVENVESLAFDWISKNLYWTDSHYKSISVMRLADKTRRTVVQYLNNPRSVVVHPFAGYL

FFTDWFRPAKIMRAWSDGSHLLPVINTTLGWPNGLAIDWAASRLYWVDAYFDKIEHSTFD

GLDRRRLGHIEQMTHPFGLAIFGEHLFFTDWRLGAIIRVRKADGGEMTVIRSGIAYILHL

KSYDVNIQTGSNACNQPTHPNGDCSHFCFPVPNFQRVCGCPYGMRLASNHLTCEGDPTNE

PPTEQCGLFSFPCKNGRCVPNYYLCDGVDDCHDNSDEQLCGTLNNTCSSSAFTCGHGECI

PAHWRCDKRNDCVDGSDEHNCPTHAPASCLDTQYTCDNHQCISKNWVCDTDNDCGDGSDE

KNCNSTETCQPSQFNCPNHRCIDLSFVCDGDKDCVDGSDEVGCVLNCTASQFKCASGDKC

IGVTNRCDGVFDCSDNSDEAGCPTRPPGMCHSDEFQCQEDGICIPNFWECDGHPDCLYGS

DEHNACVPKTCPSSYFHCDNGNCIHRAWLCDRDNDCGDMSDEKDCPTQPFRCPSWQWQCL

GHNICVNLSVVCDGIFDCPNGTDESPLCNGNSCSDFNGGCTHECVQEPFGAKCLCPLGFL

LANDSKTCEDIDECDILGSCSQHCYNMRGSFRCSCDTGYMLESDGRTCKVTASESLLLLV

ASQNKIIADSVTSQVHNIYSLVENGSYIVAVDFDSISGRIFWSDATQGKTWSAFQNGTDR

RVVFDSSIILTETIAIDWVGRNLYWTDYALETIEVSKIDGSHRTVLISKNLTNPRGLALD

PRMNEHLLFWSDWGHHPRIERASMDGSMRTVIVQDKIFWPCGLTIDYPNRLLYFMDSYLD

YMDFCDYNGHHRRQVIASDLIIRHPYALTLFEDSVYWTDRATRRVMRANKWHGGNQSVVM

YNIQWPLGIVAVHPSKQPNSVNPCAFSRCSHLCLLSSQGPHFYSCVCPSGWSLSPDLLNC

LRDDQPFLITVRQHIIFGISLNPEVKSNDAMVPIAGIQNGLDVEFDDAEQYIYWVENPGE

IHRVKTDGTNRTVFASISMVGPSMNLALDWISRNLYSTNPRTQSIEVLTLHGDIRYRKTL

IANDGTALGVGFPIGITVDPARGKLYWSDQGTDSGVPAKIASANMDGTSVKTLFTGNLEH

LECVTLDIEEQKLYWAVTGRGVIERGNVDGTDRMILVHQLSHPWGIAVHDSFLYYTDEQY

EVIERVDKATGANKIVLRDNVPNLRGLQVYHRRNAAESSNGCSNNMNACQQICLPVPGGL

FSCACATGFKLNPDNRSCSPYNSFIVVSMLSAIRGFSLELSDHSETMVPVAGQGRNALHV

DVDVSSGFIYWCDFSSSVASDNAIRRIKPDGSSLMNIVTHGIGENGVRGIAVDWVAGNLY

FTNAFVSETLIEVLRINTTYRRVLLKVTVDMPRHIVVDPKNRYLFWADYGQRPKIERSFL

DCTNRTVLVSEGIVTPRGLAVDRSDGYVYWVDDSLDIIARIRINGENSEVIRYGSRYPTP

YGITVFENSIIWVDRNLKKIFQASKEPENTEPPTVIRDNINWLRDVTIFDKQVQPRSPAE

VNNNPCLENNGGCSHLCFALPGLHTPKCDCAFGTLQSDGKNCAISTENFLIFALSNSLRS

LHLDPENHSPPFQTINVERTVMSLDYDSVSDRIYFTQNLASGVGQISYATLSSGIHTPTV

IASGIGTADGIAFDWITRRIYYSDYLNQMINSMAEDGSNRTVIARVPKPRAIVLDPCQGY

LYWADWDTHAKIERATLGGNFRVPIVNSSLVMPSGLTLDYEEDLLYWVDASLQRIERSTL

TGVDREVIVNAAVHAFGLTLYGQYIYWTDLYTQRIYRANKYDGSGQIAMTTNLLSQPRGI

NTVVKNQKQQCNNPCEQFNGGCSHICAPGPNGAECQCPHEGNWYLANNRKHCIVDNGERC

GASSFTCSNGRCISEEWKCDNDNDCGDGSDEMESVCALHTCSPTAFTCANGRCVQYSYRC

DYYNDCGDGSDEAGCLFRDCNATTEFMCNNRRCIPREFICNGVDNCHDNNTSDEKNCPDR

TCQSGYTKCHNSNICIPRVYLCDGDNDCGDNSDENPTYCTTHTCSSSEFQCASGRCIPQH

WYCDQETDCFDASDEPASCGHSERTCLADEFKCDGGRCIPSEWICDGDNDCGDMSDEDKR

HQCQNQNCSDSEFLCVNDRPPDRRCIPQSWVCDGDVDCTDGYDENQNCTRRTCSENEFTC

GYGLCIPKIFRCDRHNDCGDYSDERGCLYQTCQQNQFTCQNGRCISKTFVCDEDNDCGDG

SDELMHLCHTPEPTCPPHEFKCDNGRCIEMMKLCNHLDDCLDNSDEKGCGINECHDPSIS

GCDHNCTDTLTSFYCSCRPGYKLMSDKRTCVDIDECTEMPFVCSQKCENVIGSYICKCAP

GYLREPDGKTCRQNSNIEPYLIFSNRYYLRNLTIDGYFYSLILEGLDNVVALDFDRVEKR

LYWIDTQRQVIERMFLNKTNKETIINHRLPAAESLAVDWVSRKLYWLDARLDGLFVSDLN

GGHRRMLAQHCVDANNTFCFDNPRGLALHPQYGYLYWADWGHRAYIGRVGMDGTNKSVII

STKLEWPNGITIDYTNDLLYWADAHLGYIEYSDLEGHHRHTVYDGALPHPFAITIFEDTI

YWTDWNTRTVEKGNKYDGSNRQTLVNTTHRPFDIHVYHPYRQPIVSNPCGTNNGGCSHLC

LIKPGGKGFTCECPDDFRTLQLSGSTYCMPMCSSTQFLCANNEKCIPIWWKCDGQKDCSD

GSDELALCPQRFCRLGQFQCSDGNCTSPQTLCNAHQNCPDGSDEDRLLCENHHCDSNEWQ

CANKRCIPESWQCDTFNDCEDNSDEDSSHCASRTCRPGQFRCANGRCIPQAWKCDVDNDC

GDHSDEPIEECMSSAHLCDNFTEFSCKTNYRCIPKWAVCNGVDDCRDNSDEQGCEERTCH

PVGDFRCKNHHCIPLRWQCDGQNDCGDNSDEENCAPRECTESEFRCVNQQCIPSRWICDH

YNDCGDNSDERDCEMRTCHPEYFQCTSGHCVHSELKCDGSADCLDASDEADCPTRFPDGA

YCQATMFECKNHVCIPPYWKCDGDDDCGDGSDEELHLCLDVPCNSPNRFRCDNNRCIYSH

EVCNGVDDCGDGTDETEEHCRKPTPKPCTEYEYKCGNGHCIPHDNVCDDADDCGDWSDEL

GCNKGKERTCAENICEQNCTQLNEGGFICSCTAGFETNVFDRTSCLDINECEQFGTCPQH

CRNTKGSYECVCADGFTSMSDRPGKRCAAEGSSPLLLLPDNVRIRKYNLSSERFSEYLQD

EEYIQAVDYDWDPKDIGLSVVYYTVRGEGSRFGAIKRAYIPNFESGRNNLVQEVDLKLKY

VMQPDGIAVDWVGRHIYWSDVKNKRIEVAKLDGRYRKWLISTDLDQPAAIAVNPKLGLMF

WTDWGKEPKIESAWMNGEDRNILVFEDLGWPTGLSIDYLNNDRIYWSDFKEDVIETIKYD

GTDRRVIAKEAMNPYSLDIFEDQLYWISKEKGEVWKQNKFGQGKKEKTLVVNPWLTQVRI

FHQLRYNKSVPNLCKQICSHLCLLRPGGYSCACPQGSSFIEGSTTECDAAIELPINLPPP

CRCMHGGNCYFDETDLPKCKCPSGYTGKYCEMAFSKGISPGTTAVAVLLTILLIVVIGAL

AIAGFFHYRRTGSLLPALPKLPSLSSLVKPSENGNGVTFRSGADLNMDIGVSGFGPETAI

DRSMAMSEDFVMEMGKQPIIFENPMYSARDSAVKVVQPIQVTVSENVDNKNYGSPINPSE

IVPETNPTSPAADGTQVTKWNLFKRKSKQTTNFENPIYAQMENEQKESVAATPPPSPSLP

AKPKPPSRRDPTPTYSATEDTFKDTANLVKEDSEV(SEQ ID NO.940)。

As used herein, "target sequence" refers to a contiguous portion of the mRNA molecule nucleotide sequence formed during transcription of a gene of interest (e.g., CD320 gene or LRP2 gene), including mRNA that is the product of RNA processing of the primary transcript.

As used herein, the term "strand comprising a sequence" refers to an oligonucleotide comprising a chain of nucleotides, which is described by a sequence referred to using standard nucleotide nomenclature.

"G", "C", "A" and "U" generally each represent a nucleotide containing guanine, cytosine, adenine and uracil as bases. "T" and "dT" are used interchangeably herein and refer to deoxyribonucleotides in which the nucleobase is thymine, e.g., deoxyribothymine, 2' -deoxythymidine, or thymidine. However, it should be understood that the term "ribonucleotide" or "nucleotide" or "deoxyribonucleotide" may also refer to modified nucleotides, or alternative replacement portions, as described in further detail below. It will be apparent to those skilled in the art that guanine, cytosine, adenine and uracil may be substituted with other moieties without substantially altering the base pairing properties of oligonucleotides comprising nucleotides carrying such substituted moieties. For example, without limitation, a nucleotide containing inosine as its base may base pair with a nucleotide containing adenine, cytosine, or uracil. Thus, in the nucleotide sequence of the present invention, a nucleotide containing uracil, guanine or adenine may be replaced with a nucleotide containing, for example, inosine. Sequences comprising such replacement parts are embodiments of the present invention.

The term "siRNA" refers to the term, as defined herein, that contains an RNA compound, mixture, composition or agent that mediates targeted cleavage of an RNA transcript by a RISC/AGO (RNA-induced silencing complex) complex, whereby the guide strand of the siRNA hybridizes to the mRNA molecule to which it is complementary. mRNA is degraded by the RISC/AGO complex, which has RNase cleavage activity, resulting in mRNA degradation, and no or reduced levels of protein encoded by mRNA are produced as compared to untreated cells. This results in a "knockdown" effect or reduced protein levels of the gene targeted by the siRNA compared to control treated cells. siRNA modulates, e.g., inhibits expression of CD320 or LRP2 in a cell, e.g., a cell within a subject (such as a mammalian subject).

In one embodiment, the RNAi agents of the invention comprise single-stranded RNA that interacts with a target RNA sequence (e.g., CD320 or LRP2 target mRNA sequence) to direct cleavage of the target RNA. Without wishing to be bound by theory, it is believed that long double stranded RNA introduced into the cell is cleaved into siRNA by a type III endonuclease called Dicer (Sharp et al (2001) Genes Dev.15:485). Dicer (an rnase III-like enzyme) treats dsRNA into a short interfering RNA of 19-23 base pairs (bp) with a characteristic two base 3' overhang (Bernstein, et al, (2001) Nature 409:363). Initially, siRNA may consist of two RNA strands, an antisense (or guide) strand and a sense (or passenger) strand, which form a duplex of unequal length 10-80bp with or without 3' nucleotide overhang. The dsRNA may comprise one or more single-stranded overhangs of one or more nucleotides. In one embodiment, at least one end of the dsRNA has a single-stranded nucleotide overhang of 1 mass 4, typically 1 or 2 nucleotides. In another embodiment, the antisense strand of the dsRNA has an overhang of 1-10 nucleotides at each of the 3 'and 5' ends on the sense strand. In further embodiments, the sense strand of the dsRNA has an overhang of 1-10 nucleotides at each of the 3 'and 5' ends of the antisense strand.

The siRNA is then incorporated into an RNA-induced silencing complex (RISC), wherein one or more helices cleave the siRNA duplex, enabling the complementary antisense (guide) strand to guide target recognition (Nykanen, et al, (2001) Cell 107:309). Upon binding to the appropriate target mRNA, one or more endonucleases within RISC cleave the target to induce silencing (Elbashir, et al, (2001) Genes Dev.15:188). Thus, in one aspect, the invention relates to single stranded RNAs (sirnas) produced in cells that promote the formation of RISC complexes to cause silencing of target genes (i.e., CD320 or LRP2 genes). Thus, the term "siRNA" is also used herein to refer to RNAi as described above.

In another embodiment, the RNAi agent can be a single-stranded siRNA that is introduced into a cell or organism to inhibit a target mRNA. The single stranded RNAi agent binds to RISC endonuclease Argonaute 2 (which then cleaves the target mRNA). Single-stranded siRNA is typically 15-80 nucleotides and can be chemically modified to improve metabolic stability and activity; wherein one or more pyrimidine nucleotides may be modified to a 2' -deoxy-2 ' -fluoro nucleotide, one or more purine nucleotides may be modified to a 2' -deoxy purine nucleotide, further wherein a terminal cap modification may be present at the 3' or 5' end; in particular by introducing one or more 2' -deoxythymidine nucleotides, or by introducing one or more phosphorothioate groups at any nucleotide in the linker sequence but in particular at the 3' and 5' ends. In addition, 3' -terminal phosphate or vinyl phosphonate groups may be introduced. Examples of such modifications include, but are not limited to, modifications to the ribose moiety of a nucleotide, such as: other modifications to the ribose moiety may include bridging modifications such that the 2 '-carbon of the sugar moiety is covalently linked to the 4' -carbon of the sugar moiety through a methylene or methoxymethylene group to provide bridged nucleotides described in the art as LNA and (S) -cET respectively (corey et al., (2018) nuc acid res 46; 1584-1600). Furthermore, the sugar moiety may be modified by removing the bond between carbon C2 'and C3' to provide "open" chain nucleotides similar to those described in WO 2011/139843 A2. The ribose moiety of the RNA nucleotide may also be substituted with morpholino groups to provide modifications of the phosphodiester moiety of the PMO nucleotide and may also include phosphorothioate and phosphorothioate (32, 32) and phosphorothioate (32, 37-3882) which may be replaced with phosphorothioate, such as the end of the phosphorothioate, and the end of the phosphorothioate may be modified by the use of the phosphorothioate (32, 32-3882) in addition, the end of the phosphorothioate and the phosphorothioate may be replaced with a phosphorothioate (32, 35) of the end of the phosphorothioate and the phosphorothioate may be modified by the phosphorothioate of the end of the phosphorothioate (32, 35). (2012) Cell150:883-894 (each of which is incorporated herein by reference in its entirety). Any of the antisense nucleotide sequences described herein can be used as a single stranded siRNA described herein, or by Lima et al, (2012) Cell 150; 883-894.

In another embodiment, the "RNAi" used in the compositions, uses and methods of the invention is double-stranded RNA, and is referred to herein as a "double-stranded RNAi agent," double-stranded RNA (dsRNA) molecule, "" dsRNA agent, "or" dsRNA. The term "dsRNA" refers to a complex of ribonucleic acid molecules having a duplex structure comprising two antiparallel and substantially complementary nucleic acid strands, which are said to have "sense" (passenger) and "antisense" (guide) orientations relative to a target RNA (i.e., CD320 gene or LRP2 gene). In some embodiments of the invention, double-stranded RNA (dsRNA) triggers degradation of target RNA (e.g., mRNA) by a post-transcriptional gene silencing mechanism referred to herein as RNA interference or RNAi.

Typically, the majority of the nucleotides of each strand of a dsRNA molecule are ribonucleotides, but as described in detail herein, each or both strands may also comprise one or more non-ribonucleotides, e.g. deoxyribonucleotides and/or modified nucleotides. Furthermore, as used herein, an "RNAi agent" may comprise ribonucleotides with chemical modification (Corey et al., (2018) Nuc Acid Res46; 1584-1600); RNAi agents can comprise substantial modifications at multiple nucleotides or at a single nucleotide. Such modifications may include all types of modifications disclosed herein or known in the art. Any such modification used in siRNA-type molecules is encompassed within the "RNAi agents" for the purposes of this specification and claims. Examples of such modifications include, but are not limited to, modifications to the ribose moiety of a nucleotide, such as: other modifications to the ribose moiety may include bridging modifications such that the 2 '-carbon of the sugar moiety is covalently linked to the 4' -carbon of the sugar moiety through A methylene or methoxymethylene group to provide bridging nucleotides described in the art as LNA and (S) -cET respectively (corey et al., (2018) nuc acid res46; 1584-1600). Furthermore, the sugar moiety may be modified by removing the bond between carbon C2 'and C3' to provide "open" strand nucleotides similar to those described in WO 2011/139843A 2. The ribose moiety of an RNA nucleotide may also be substituted with morpholino groups to provide modifications of the phosphodiester moiety of A PMO nucleotide and may also include phosphorothioate and phosphorothioate (35) alternative to the phosphorothioate end of the nucleotide, such as the phosphorothioate end of fig. 35-35, and the phosphorothioate end may be replaced with A phosphorothioate end of the phosphorothioate (35, 35-35).

Chemical modification of ribonucleotides can be performed at any single nucleotide or combination of nucleotides in the antisense and sense strands. In some cases, all nucleotides in the antisense strand or the sense strand, or both the antisense and sense strands, are chemically modified (Allerson et al., (2005) J Med Chem 48, 901-904). In other cases, only some of the nucleic acids in the antisense strand or sense strand, or in both the antisense and sense strands, are chemically modified (Chiu et al, (2003) RNA 9,1034-1048). In still other cases, the modification may follow a pattern of alternating 2 '-methoxy and 2' -fluoro modifications to one or both strands of the siRNA, and sometimes the complementary nucleotides of the antisense strand and sense strand may contain different chemical modifications, e.g., where one member of the complementary nucleotide pair has a 2 '-methoxy modification and the other member has a 2' -fluoro modification (Choung et al.(2006)Biochem Biophys Res Commun 342,919-927;Hassler et al.,(2018)Nucleic Acid Res 46,2185-2196).

The two strands forming the duplex structure may be different parts of one larger RNA molecule, or they may be separate RNA molecules. In the case where the two strands are part of one larger molecule, and thus are joined by an uninterrupted nucleotide chain between the 3 'end of one strand and the corresponding 5' end of the other strand to form a double-stranded structure, the joined RNA strands are referred to as "hairpin loops". In the case where the two strands are covalently linked by other means than an uninterrupted nucleotide chain between the 3 'end of one strand and the corresponding 5' end of the other strand to form a duplex structure, the linking structure is referred to as a "linker". The RNA strands may have the same or different numbers of nucleotides. The maximum number of base pairs is the number of nucleotides in the shortest strand of the dsRNA minus any overhangs present in the duplex. In addition to duplex structures, RNAi agents can comprise one or more nucleotide overhangs.

In one embodiment, the RNAi agent of the invention is a 20-30 nucleotide dsRNA that interacts with a target RNA sequence, such as a CD320 target mRNA sequence or an LRP2 target mRNA sequence, to direct cleavage of the target RNA.

The term "antisense strand" refers to the following strand of a double stranded RNAi agent: comprising a region substantially complementary to a target sequence (e.g., human CD320 mRNA or LRP2 mRNA). As used herein, the term "region complementary to a portion of an mRNA encoding CD320 or LRP 2" refers to a region on the antisense strand that is substantially complementary to a portion of an mRNA sequence encoding CD320 or LRP 2. Where the complementary region is not perfectly complementary to the target sequence, mismatches are most acceptable in the terminal region and, if present, are typically in one or more terminal regions, e.g., within 6, 5, 4, 3 or 2 nucleotides of the 5 'and/or 3' end. For example, in certain embodiments, substantially complementary may mean that in a hybridization pair of nucleobase sequences, at least 85% but not all of the bases in a contiguous sequence of a first polynucleotide will hybridize to the same number of bases in a contiguous sequence of a second polynucleotide.

The term "sense strand" as used herein refers to the following strand of dsRNA: comprising a region substantially complementary to a region of the antisense strand.

As used herein, the term "cleavage region" refers to a region located immediately adjacent to a cleavage site. The cleavage site is the site on the target where cleavage occurs. In some embodiments, the cleavage region comprises three bases on either end of the cleavage site and immediately adjacent to the cleavage site. In some embodiments, the cleavage region comprises two bases on either end of the cleavage site and immediately adjacent to the cleavage site. In some embodiments, cleavage sites occur specifically at the site where nucleotides 10 and 11 of the antisense strand bind, and cleavage regions Bao Han nucleotides 11, 12, and 13.

As used herein, the term "complementary" when used in reference to a first nucleotide sequence in relation to a second nucleotide sequence, refers to the ability of an oligonucleotide or polynucleotide comprising the first nucleotide sequence to hybridize to and form a duplex structure with an oligonucleotide or polynucleotide comprising the second nucleotide sequence under certain conditions, as understood by one of skill in the art, unless otherwise indicated. For example, such conditions may be stringent conditions, where stringent conditions may include: the washing is carried out after a duration of 12-16 hours at 400mM NaCl,40mM PIPES pH 6.4,1mM EDTA,50 ℃or 70 ℃. Other conditions, such as physiologically relevant conditions that may be encountered in an organism, may also be suitable. For example, the complementary sequence is sufficient to allow the relevant function of the nucleic acid to proceed, such as RNAi. One skilled in the art will be able to determine the set of conditions best suited for testing the complementarity of two sequences depending on the end use of the hybridizing nucleotides.

Sequences may be "fully complementary" with respect to each other when there is a base pairing of a nucleotide of a first nucleotide sequence with a nucleotide of a second nucleotide sequence over the entire length of the first and second nucleotide sequences. However, when a first sequence is referred to herein as "substantially complementary" to a second sequence, the two sequences may be fully complementary, or they may form one or more, but typically no more than 4, 3 or 2 mismatched base pairs upon hybridization, while retaining the ability to hybridize under conditions most relevant to their end use. However, where two oligonucleotides are designed to form one or more single stranded overhangs upon hybridization, such overhangs should not be considered mismatches in determining complementarity. For example, a dsRNA comprising one oligonucleotide of 21 nucleotides in length and another oligonucleotide of 23 nucleotides in length, wherein the longer oligonucleotide comprises 21 nucleotide sequences that are fully complementary to the shorter oligonucleotide, may still be referred to as "fully complementary" for the purposes described herein.

As used herein, a "complementary" sequence may also comprise or be formed entirely of base pairs other than Watson-Crick base pairs and/or base pairs formed of non-natural and modified nucleotides, insofar as the requirements set forth above with respect to its hybridization capability are met. Such non-Watson-Crick base pairing includes, but is not limited to, G: U Wobble or Hoogstein base pairing.

The terms "complementary", "fully complementary" and "substantially complementary" herein may be used with respect to base matching between the sense strand and the antisense strand of a dsRNA, or between the antisense strand and the target sequence of a dsRNA, as will be understood from the context of their use.

As used herein, a polynucleotide that is "substantially complementary to at least a portion of a messenger RNA (mRNA) refers to a polynucleotide that is substantially complementary to a contiguous portion of an mRNA of interest (e.g., an mRNA encoding CD320 or an mRNA encoding LRP 2) that includes a 5'utr, an Open Reading Frame (ORF), or a 3' utr. For example, if the sequence is substantially complementary to an uninterrupted portion of an mRNA encoding CD320 or LRP2, the polynucleotide is complementary to at least a portion of the CD320 mRNA or LRP2 mRNA.

As used herein, the term "inhibit" is used interchangeably with "reduce," "silence," "down-regulate," "repression," and other similar terms, and includes any level of inhibition.

The phrases "inhibit expression of CD 320", "inhibit expression of LRP 2", as used herein, include inhibiting expression of any CD320 or LRP2 gene (such as an identified gene from, for example, a mouse, rat, monkey, or human), as well as variants (e.g., naturally occurring variants), or mutants of the identified gene. Thus, the CD320 or LRP2 gene may be a wild-type CD320 or LRP2 gene, a mutant CD320 or LRP2 gene, or a transgenic CD320 or LRP2 gene in the context of a genetically manipulated cell, group of cells, or organism.

"Inhibiting expression of a CD320 gene" or "inhibiting expression of an LRP2 gene" includes inhibition of any level of a CD320 gene or LRP2 gene, e.g., at least partial inhibition of gene expression of CD320 or LRP2, such as inhibition of at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%. In a preferred embodiment, inhibition is assessed by expressing the level of CD320 or LRP2 protein in the treated cells as a percentage of the mRNA level in the control cells using the following formula:

Normalized protein level of treated cells/normalized protein level of control cells. The control cells were negative control siRNA. Normalization refers to normalizing protein levels to the levels of housekeeping proteins.

Expression of the CD320 or LRP2 gene can be assessed based on the level of any variable associated with CD320 or LRP2 gene expression (e.g., CD320 or LRP2 mRNA level, CD320 or LRP2 protein level). Inhibition may be assessed by a decrease in the absolute or relative level of one or more of these variables compared to a control level. The control level may be any type of control level used in the art, e.g., a pre-dosing baseline level, or a level determined from an analogous subject, cell or sample, either untreated or treated with a control (such as, e.g., a buffer-only control or inactive reagent control).

Contacting the cells with an RNAi agent (ds or ss as used herein) includes contacting the cells by any possible means, whether in vivo or in vitro. Contacting the cell with the RNAi agent comprises contacting the cell with the RNAi agent in vitro or contacting the cell with the RNAi agent in vivo. The contacting may be performed directly or indirectly. Thus, for example, an RNAi agent can be brought into physical contact with a cell by an individual performing the method, or alternatively, the RNAi agent can be placed in conditions that would allow or result in its subsequent contact with the cell.

As used herein, "patient" or "subject" is intended to include a human or non-human animal, preferably a mammal, such as a monkey. Most preferably, the subject or patient is a human.

As used herein, "CD 320-related disease" is intended to include any disease associated with perturbation of the CD320 gene or protein, polymorphisms, single Nucleotide Polymorphisms (SNPs), and epigenetic modifications of the CD320 gene. Such diseases may be caused, for example, by overproduction of the CD320 protein, by mutation of the CD320 gene, by abnormal cleavage of the CD320 protein, by abnormal folding of the CD320 protein, by abnormal interactions between CD320 itself or with other proteins or other endogenous or exogenous substances. For example, the cancer may be a CD 320-related disease. The extent of inhibition of protein expression can be measured by western blotting.

As used herein, "LRP2 associated disease" is intended to include any disease associated with perturbation of the epigenetic modifications of the LRP2 gene, protein, polymorphism, SNP, and CD320 gene. Such diseases may be caused, for example, by overproduction of LRP2 protein, by mutation of the LRP2 gene, by abnormal cleavage of LRP2 protein, by abnormal folding of LRP2 protein, by abnormal interactions between LRP2 molecule and other proteins or other endogenous or exogenous substances. For example, the cancer may be an LRP2 associated disease. The extent of inhibition of protein expression can be measured by western blotting.

As used herein, "therapeutically effective amount" is intended to include an amount of RNAi agent that, when administered to a cell or patient for treating a CD 320-related disease or LRP 2-related disease, is sufficient to affect treatment of the disease (e.g., by reducing, ameliorating or maintaining an existing disease or one or more symptoms of the disease, or by preferably causing death of the disease cell as compared to a non-disease cell). The "therapeutically effective amount" may vary from one to the next: RNAi agents, how the agents are administered, the disease and its severity and history, age, weight, family history, genetic constitution, the stage of the pathological process mediated by CD320 or LRP2 expression, the type of previous or concomitant therapy (if any) and other individual characteristics of the patient to be treated.

As used herein, "prophylactically effective amount" is intended to include an amount of RNAi agent sufficient to prevent or ameliorate a CD 320-related disease or a symptom of LRP 2-related disease when administered to a subject who has not experienced or exhibited the disease, but who is likely to be susceptible to the disease. Improving a disease includes slowing the progression of the disease or reducing the severity of later-developed disease. The "prophylactically effective amount" may vary from: RNAi agents, how the agents are administered, the degree of risk of disease, medical history, age, body weight, family history, genetic make-up, type of previous or concomitant therapy (if any), and other individual characteristics of the patient to be treated.

"Therapeutically effective amount" or "prophylactically effective amount" also includes the amount of RNAi agent that produces some desired local or systemic effect at a reasonable benefit/risk ratio applicable to any treatment. The RNAi agents used in the methods of the invention can be administered in sufficient amounts to produce a reasonable benefit/risk ratio suitable for such treatment.

Pharmaceutical composition

The methods described herein comprise administering an LRP2 inhibitory composition and/or a CD320 inhibitory composition, e.g., a first siRNA targeting the CD320 gene and/or a second siRNA targeting the LRP2 gene. In some embodiments, the LRP2 inhibiting composition and/or the CD320 inhibiting composition is a pharmaceutical composition.

The methods described herein further comprise administering one or more LRP2 inhibiting compositions and/or one or more CD320 inhibiting compositions, e.g., one or more sirnas targeting the CD320 gene and/or one or more sirnas targeting the LRP2 gene. It will be appreciated that such compositions may be chemically modified in a variety of ways and that such modifications need not be the same in the composition mixture. In some embodiments, the LRP2 inhibiting composition and/or the CD320 inhibiting composition is a pharmaceutical composition.

The pharmaceutical compositions of the present invention may be administered in a variety of ways depending on whether local or systemic treatment is desired or not, and the area to be treated. Administration may be topical, pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer); intratracheal, intranasal, epidermal and transdermal, oral or parenteral. Parenteral administration includes intravenous, intra-arterial, subcutaneous, intraperitoneal, or intramuscular injection or infusion; or intracranial, such as intraparenchymal, intrathecal, or intraventricular administration.

The composition may be delivered in a manner that targets specific tissues such as lung cells or breast cells or brain cells or bladder cells or uterine cells or cervical cells or prostate cells. The pharmaceutical composition may be delivered directly into the brain by injection. The injection may be stereotactically injected into a specific region of the brain (e.g., substantia nigra, cortex, hippocampus, striatum, or globus pallidus), or the dsRNA may be delivered into multiple regions of the central nervous system (e.g., into multiple regions of the brain, and/or into the spinal cord). dsRNA may also be delivered into a diffuse region of the brain (e.g., diffusion delivered to the cortex of the brain). Typically, siRNA is administered 1) by intratumoral injection, 2) by systemic injection, 3) by slow release from the implanted polymer. Other tissue specificities may be achieved by antibody or small molecule conjugation, or by tissue-specific delivery devices (e.g., catheters may be used for delivery to the bladder).

In one embodiment, RNAi targeting LRP2 or CD320 can be delivered through a cannula or other delivery device having one end implanted in tissue. The cannula may be connected to a reservoir of the RNAi composition. Flow or delivery may be mediated by a pump, such as an osmotic pump or a micropump. In one embodiment, the pump and reservoir are implanted away from the region of tissue, such as in the abdomen, and delivery is effected by a catheter leading from the pump or reservoir to the release site.

Thus, in some embodiments, the pharmaceutical compositions described herein comprise one or more pharmaceutically acceptable excipients. The pharmaceutical compositions described herein are formulated for administration to a subject.

As used herein, a pharmaceutical composition or medicament comprises a pharmacologically effective amount of at least one of the RNAi agents and one or more pharmaceutically acceptable excipients. Pharmaceutically acceptable excipients (excipients) are substances other than the active pharmaceutical ingredient (API, therapeutic product, e.g., CD320 RNAi agent or LRP2 RNAi agent) that are intentionally included in a drug delivery system. Excipients do not exert or are not intended to exert a therapeutic effect at the intended dose. The excipient may function as follows: a) facilitates handling of the drug delivery system during manufacture, b) protects, supports or enhances stability, bioavailability or patient acceptability of the API, c) facilitates product identification, and/or d) enhances any other attribute of the overall safety, effectiveness of API delivery during storage or use. The pharmaceutically acceptable excipient may or may not be an inert substance.

Excipients include, but are not limited to: absorption enhancers, anti-adherent agents, defoamers, antioxidants, binders, buffers, carriers, coating agents, colorants, delivery enhancers, delivery polymers, dextran, dextrose, diluents, disintegrants, emulsifiers, extenders, fillers, flavoring agents, glidants, humectants, lubricants, oils, polymers, preservatives, saline, salts, solvents, sugars, suspending agents, slow release matrices, sweeteners, thickeners, tonicity agents, vehicles, water repellents, and wetting agents.

Pharmaceutical compositions suitable for injectable use comprise sterile aqueous solutions (in the case of water solubility) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, cremophor. RTM. ELTM (BASF, parsippany, N.J.), or Phosphate Buffered Saline (PBS). The composition is understood to include formulations and drug delivery systems, should be stable under the conditions of manufacture and storage, and should be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), and suitable mixtures thereof. For example, proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants. In many cases, it is preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, and sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition agents which delay absorption, for example, aluminum monostearate and gelatin.

Sterile injectable solutions can be prepared by: the desired amount of active compound is incorporated, if desired, in an appropriate solvent with one or a combination of the ingredients listed above, and then filter sterilized. Typically, dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the methods of preparation include vacuum drying and freeze-drying which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

Formulations suitable for intra-articular administration may be in the form of a sterile aqueous preparation of the drug, which may be in microcrystalline form, for example, in the form of an aqueous microcrystalline suspension. Liposome formulations or biodegradable polymer systems can also be used to present drugs for intra-articular and ophthalmic administration.

Active compounds, such as controlled release formulations, including implants and microcapsule delivery systems, can be prepared with carriers that protect the compound from rapid elimination in vivo. Biodegradable biocompatible polymers such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid may be used. Methods for preparing such formulations will be apparent to those skilled in the art. Liposomal suspensions may also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No.4,522,811.

Dose and timing

Those of skill in the art will appreciate that certain factors may affect the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or condition, previous treatments, the overall health and/or age of the subject, and other diseases present. Furthermore, treating a subject with a therapeutically effective amount of a composition may include monotherapy or a series of therapies. The effective dosages and in vivo half-life estimates of LRP2 inhibitory and/or CD320 inhibitory compositions encompassed by the present invention can be made using conventional methods or based on in vivo testing using an appropriate animal model, as described elsewhere herein.

Generally, a suitable dose of a pharmaceutical composition of an LRP2 inhibitory composition and/or a CD320 inhibitory composition will be in the range of 0.01 to 300.0 mg/kg body weight of the subject per day, typically in the range of 1 to 50 mg/kg body weight per day.

For example, the LRP2 inhibiting composition and/or the CD320 inhibiting composition may be an siRNA composition of one or more sirnas and may be administered at 0.01mg/kg、0.05mg/kg、0.2mg/kg、0.3mg/kg、0.4mg/kg、0.5mg/kg、0.6mg/kg、0.7mg/kg、0.8mg/kg、0.9mg/kg、1mg/kg、1.1mg/kg、1.2mg/kg、1.3mg/kg、1.4mg/kg、1.5mg/kg、1.628mg/kg、2mg/kg、3mg/kg、5.0mg/kg、10mg/kg、20mg/kg、30mg/kg、40mg/kg、50mg/kg、100mg/kg、200mg/kg、400mg/kg per single dose. In another embodiment, the dosage is from 0.15mg/kg to 0.3mg/kg. For example, an LRP2 and/or CD320 inhibitory composition may be administered at a dose of 0.15mg/kg, 0.2mg/kg, 0.25mg/kg, or 0.3mg/kg. In one embodiment, the LRP2 and/or CD320 inhibitory composition is administered at a dose of 0.3mg/kg.

The pharmaceutical composition may be administered once daily, or once or twice every 5, 10, 15, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days. The dosage units may be compounded to deliver within a few days, for example, using conventional sustained release formulations that provide sustained release of the LRP2 inhibiting composition and/or CD320 inhibiting composition over a period of several days. Sustained release formulations are well known in the art and are particularly suitable for delivering agents at a particular site, such as may be used with the agents of the present invention.

In one embodiment, the LRP 2-inhibitory composition and/or the CD 320-inhibitory composition is dependent on the tumor cell line at a dose of 0.3mg/kg, and wherein one dose is administered every 21 days. In another embodiment, the effective amount is 0.3mg/kg and the effective amount is administered once every 21 days by infusion for 70 minutes (15 minutes at 1mL/min, then 55 minutes at 3 mL/min). In another embodiment, the effective amount is 0.3mg/kg and the effective amount is administered in two doses every 21-28 days by 60 minutes of infusion (at 3.3 mL/min) or by 70 minutes of infusion (at 1.1mL/min for 15 minutes and then at 3.3mL/min for 55 minutes).

Dosages of the LRP2 inhibitory composition and/or CD320 inhibitory composition may be adjusted for treatment.

The LRP 2-inhibitory composition and/or CD 320-inhibitory composition may be administered in combination with other known drugs effective in treating pathological processes mediated by target gene expression.

In another embodiment, the pharmaceutical composition is formulated for administration according to the dosage regimen described herein, e.g., no more than once every four weeks, no more than once every three weeks, no more than once every two weeks, or no more than once a week. In another embodiment, administration of the pharmaceutical composition may be maintained for one month or more, such as one month, two months, three months, or six months, or one year or more.

In embodiments of the pharmaceutical compositions described herein, RNAi (e.g., dsRNA) is administered with a buffer solution. In an embodiment, the buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate, or any combination thereof. In an embodiment, the buffer solution is Phosphate Buffered Saline (PBS).

In embodiments of the pharmaceutical compositions described herein, the compositions are administered intravenously.

In embodiments of the pharmaceutical compositions described herein, the composition is administered subcutaneously.

In certain embodiments, the pharmaceutical compositions, e.g., the compositions described herein, comprise lipid formulations. In embodiments, the composition is administered intravenously.

In some embodiments, a pharmaceutical composition, such as the compositions described herein, comprises a cationic polyamine formulation or nanoparticle (e.g., jetPEI). In some embodiments, the composition is administered intravenously.

In another embodiment, the pharmaceutical composition is formulated for administration according to the dosage regimen described herein, e.g., no more than once every four weeks, no more than once every three weeks, no more than once every two weeks, or no more than once a week. In another embodiment, administration of the pharmaceutical composition may be maintained for one month or more, for example, one month, two months, three months, or six months, or one year or more.

In another embodiment, a composition containing an RNAi agent (e.g., dsRNA targeting LRP2 or CD 320) characteristic of the invention is administered with a non-RNAi therapeutic agent such as an agent known to be useful in treating cancer such as lung cancer. In another embodiment, a composition containing a characteristic RNAi agent of the invention (e.g., a dsRNA targeting LRP2 and/or CD 320) is administered with a non-RNAi therapeutic regimen, such as radiation therapy, chemotherapy, immunotherapy, photodynamic therapy, or a combination thereof.

In one aspect provided herein is a method of inhibiting LRP2 and/or CD320 expression in a cell, the method comprising: (a) Introducing an RNAi agent (e.g., dsRNA) as described herein into a cell and (b) maintaining the cell of step (a) for a time sufficient to obtain degradation of mRNA transcripts of the LRP2 gene and/or the D320 gene, thereby inhibiting expression of the LRP2 gene and/or the CD320 gene in the cell.

In one aspect provided herein is a method for reducing or inhibiting expression of an LRP2 gene and/or a CD320 gene in a cell. The method comprises the following steps: (a) One or more complementary double-stranded ribonucleic acid (dsRNA) molecules in which one sequence is designated the sense strand and the other sequence is designated the antisense strand, and wherein the antisense strand has significant complementarity to a portion of the mRNA encoding LRP2 or CD320, are introduced into the cell. The complementary region is 15-30 nucleotides in length, and typically 19-24 nucleotides in length, and the dsRNA inhibits expression of LRP2 protein and/or D320 protein by at least 10%, such as at least 20%, at least 30%, at least 40% or more upon entry into a cell expressing LRP2 and/or CD 320; (b) Single or repeated treatment of cells with dsRNA as described in part (a) to maintain inhibition of LRP2 and/or CD320 protein expression for a desired period of time of at least 10%, e.g., at least 20%, at least 30%, at least 40% or more.

In an embodiment of the above method of inhibiting LRP2 and/or CD320 expression in a cell, the cell is treated ex vivo, in vitro or in vivo. In embodiments, the cell is melanoma, glioblastoma, lung cancer, triple negative breast cancer, kidney cancer, pancreatic cancer, hepatocellular carcinoma, ovarian cancer, and prostate cancer.

In some embodiments, the cells are present in a subject in need of treatment, prevention and/or management of a CD 320-associated disease or LRP 2-associated disease.

In embodiments, expression of LRP2 and/or CD320 is inhibited by at least 30%.

In embodiments, IC ₅₀ of RNAi (e.g., dsRNA) is in the range of 0.01-50 nM.

In embodiments, IC ₅₀ of RNAi (e.g., dsRNA) is in the range of 0.01-1 nM.

In certain embodiments, the cell is a mammalian cell (e.g., a human, non-human primate, or rodent cell).

In one embodiment, the cells are treated ex vivo, in vitro, or in vivo (e.g., the cells are present in a subject (e.g., a patient in need of treatment, prevention, and/or management of a disease associated with LRP2 and/or CD320 expression).

In one embodiment, the subject is a mammal (e.g., a human) at risk of, or diagnosed with, a proliferative disorder.

In embodiments, RNAi (e.g., dsRNA) is formulated as a Lipid Nanoparticle (LNP) multi-complex (polyamine) formulation.

In embodiments, RNAi (e.g., dsRNA) is administered at a dose of 0.05001-500.01 mg/kg.

In embodiments, RNAi (e.g., dsRNA) is administered at a concentration of 0.01mg/kg to 50.1mg/kg of subject body weight.

In embodiments, RNAi (e.g., dsRNA) is formulated as an LNP formulation and administered at a dose of 0.050.1-50.5 mg/kg.

In embodiments, IC ₅₀ of RNAi (e.g., dsRNA) is in the range of 0.01-10 nM.

In embodiments, RNAi (e.g., dsRNA) or a composition comprising RNAi is administered according to a dosing regimen. In embodiments, RNAi (e.g., dsRNA) or a composition comprising RNAi is administered in a single dose or in multiple doses, e.g., according to a dosage regimen.

As used herein, the term "sample" includes a collection of fluids, cells, or tissues isolated from a subject, as well as fluids, cells, or tissues present in the subject. Examples of biological fluids include blood, serum and serosal fluids, plasma, cerebrospinal fluid, ocular fluid, lymph, urine, saliva, and the like. Tissue samples may include samples from tissues, organs or local areas. For example, the sample may originate from a particular organ, a portion of an organ, or fluid or cells within those organs. In certain embodiments, the sample may be derived from a tumor. In a preferred embodiment, "sample derived from a subject" refers to blood or plasma drawn from a subject. In further embodiments, "sample derived from a subject" refers to a tissue biopsy derived from a subject.

In one embodiment, a characteristic RNAi (e.g., dsRNA) herein comprises a first sequence of dsRNA selected from the group consisting of the sense sequences of table 1 and a second sequence selected from the group consisting of the corresponding antisense sequences of table 1. It should be understood that the suffix a (e.g., OSC 17A) represents the antisense strand and the suffix S (e.g., OSC 17S) represents the sense strand. In those cases, when we refer to siRNA without a suffix (e.g., OSC 17), we mean dsRNA consisting of an antisense strand and a sense strand corresponding to the number (e.g., OSC17A paired with OSC 17S).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, while in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. RNAi targeting CD320 inhibits expression of CD320 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more when contacted with a cell expressing CD320, such as when determined by a method as described herein. In one embodiment, the CD 320-targeting RNAi is formulated in Stabilized Nucleic Acid Lipid Particles (SNALP).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, while in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. RNAi targeting LRP2 inhibits expression of LRP2 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35% or at least 40% or more when contacted with cells expressing LRP2, such as when determined by the methods as described herein. In one embodiment, the RNAi targeting LRP2 is formulated in Stabilized Nucleic Acid Lipid Particles (SNALP).

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, while in other embodiments, the RNAi is about 25 to about 30 nucleotides in length. RNAi targeting CD320 inhibits expression of CD320 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35%, or at least 40% or more when contacted with a cell expressing CD320, such as when determined by a method as described herein. In one embodiment, the CD320 targeted RNAi is formulated as a complex with a cationic polyamine, which may be present as nanoparticles.

In some embodiments, the RNAi is about 15 to about 25 nucleotides in length, while in other embodiments the RNAi is about 25 to about 30 nucleotides in length. RNAi targeting LRP2 inhibits expression of LRP2 gene by at least 10%, at least 20%, at least 25%, at least 30%, at least 35% or at least 40% or more when contacted with cells expressing LRP2, such as when determined by the methods as described herein. In one embodiment, LRP 2-targeting RNAi is formulated with cationic polyamines as a complex, which may be present as nanoparticles.

Referring now to table 1-the DNA sequence is illustrated, which is then transcribed into shRNA, targeting CD320 or LRP2 mRNA for disruption in the cell. The shRNA sequences used in lentiviral vectors exemplify sequences for targeting CD320 sequences encoding CD320 proteins and LRP2 sequences encoding LRP2 proteins. Each vector carrying the shRNA coding sequence also contains a unique drug resistance gene that will allow selection of those cells that ingest shRNA because those cells that do not ingest shRNA with unique drug resistance gene will not survive. Drug selection was initiated on day 2. On day 3, cells were harvested and plated in new dishes. Only cells with drug resistance genes, i.e. those that ingest shRNA virus particles, survive this re-plating procedure. From day 4, the cell growth of each culture was closely observed. Cells infected with unrelated control shRNA continued to grow as expected (since shRNA is essentially a nonfunctional shRNA) -data not shown. The results of cell lines that ingest cd320+lrp2shrna are shown in table 1.

TABLE 1

Preliminary studies showed that cancer cells were selectively killed by CD320 and LRP2 knockdown, while normal cells remained unaffected (table 2).

Table 2 shows the effect of simultaneous knockdown of CD320 and LRP2 on cell viability.

TABLE 2

Additional cancer cell lines were also treated with the compounds described herein to determine whether the cancer cell lines were more susceptible to growth inhibition and toxicity than non-cancer cells of the same origin. Similar to the experimental overview in fig. 1, cell lines from skin cancer, prostate cancer and brain cancer were screened. Table 3 summarizes the effect of simultaneous knockdown of CD320 and LRP2 in cancer and normal cells.

TABLE 3 Table 3

Screening results showed that lung, prostate, skin and brain cancer cell lines were inhibited or killed by simultaneous knockdown of CD320 and LRP2 ("double knockdown"), while non-cancerous cells were unaffected.

Referring now to fig. 2, representative photographs of cells were taken to record their phenotype after double knockdown of CD320 and LRP2 and to illustrate the sensitivity of cancer cell lines to knockdown of CD320 and LRP2 protein expression.

As described in fig. 1, normal cells (GM 05659 fibroblasts) or cancer cells were infected with lentiviruses for control sequences or for shRNA expression by shCD320 and shLRP. Cells were grown as described in fig. 1. On day 9 after transfection with lentiviruses, photographs of the cells were taken. The solid oval represents healthy growth of normal fibroblasts infected with shRNA against CD320 and LRP 2. The dashed ellipses represent unhealthy dead cells of the cancer cell line infected with shRNA against CD320 and LRP 2.

These results support the use of compounds as therapeutic agents based on reduced expression of CD320 and LRP2 proteins, preferably resulting in detrimental effects in cancer cells compared to non-cancer cells. Initial experiments were performed using shRNA delivered by lentiviral vectors. Short inhibitory RNAs (sirnas) were designed with sequences complementary to a portion of CD320 protein and/or LRP2 protein. siRNA can be chemically modified to increase its stability and efficacy and reduce its immunogenicity, and there are a variety of platforms for its delivery in clinical applications.

SiRNA sequences were designed and identified that were effective in knocking down protein levels of LRP2 and/or CD 320. Table 4 is a list of siRNA sequences complementary to mRNA of CD320 or LRP2, which were tested for their ability to knock down CD320 or LRP2 protein, respectively (see fig. 3, 4, 5, 12 and 15).

TABLE 4 Table 4

The list of all potential siRNA sequences is quite large. We have identified 340 potential siRNA sequences against LRP2 and 59 potential siRNA sequences against CD 320. (for the complete list see tables 5 and 6, tables 5A and 6A identify, for each antisense sequence identified, complementary target positions and sequences). In addition, these siRNA sequences can be chemically modified to improve their stability and reduce their off-target effects. siRNA molecules are susceptible to metabolic degradation, for example by rnases or dnases. The siRNA can be made resistant to such metabolic degradation and increase its biological half-life in cells or plasma by chemically modifying the siRNA molecule by incorporating one or more non-natural (i.e., artificial) nucleotides in the sequence. In addition, inclusion of artificial nucleotides at strategic positions in the siRNA sequence can reduce the immunogenicity of the siRNA and increase the selectivity of the guide strand relative to the passenger strand. The modified siRNA molecules may bind a single type of artificial nucleotide, or may comprise multiple artificial nucleotides of different types. Artificial nucleotides may include, but are not limited to, those containing chemical modifications to the ribose moiety or phosphate moiety (fig. 19 and table 7). Examples of artificial nucleotides include, but are not limited to, the structures shown in table 7. Further, modifications of a plurality of structural elements may be combined. In addition, nucleobase B may be modified, which may include unnatural bases such as those containing sulfur atoms (e.g., thiouracil) in addition to natural RNA nucleobases (G, C, a, U).

TABLE 7 nucleotide modifications corresponding to FIG. 19A

^a N represents any ribonucleotide or deoxyribonucleotide or analogue thereof.

In some embodiments, the phosphodiester group covalently linking two nucleotides is chemically modified such that, for example, one or both oxygen atoms in the group are replaced with sulfur atoms (as indicated by a single or double asterisk between the two nucleotides) to indicate that one or both oxygen atoms in the phosphodiester are replaced with sulfur (table 7 and fig. 19A). In some embodiments, the siRNA sequence may comprise other artificial nucleotides in which further structural modifications have been made to the ribose moiety, such as the addition of bridging atoms covalently linking carbons 2 'and 5' of the ribose moiety (fig. 19B-C fig. 19) or positions 1 'and 2' of the ribose moiety (fig. 19D), or alternatively, changes in the size of the sugar ring in a given nucleotide, such as the deletion of the bond between carbons 2 'and 3' of the ribose moiety (fig. 19E), or an increase in the size of the sugar ring from 5 atoms to 6 atoms (fig. 19F-19G).

TABLE 5CD320

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TABLE 6LRP2

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Table 5A CD320 antisense targets

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Table 6a LRP2 antisense targets

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TABLE 11

Additional tables of siRNA sequences

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Modified keywords

[ DT ] = DNA base (T) in RNA oligo

[ MA ], [ mG ], [ mC ], [ mU ] = 2' O-methyl RNA

* =Phosphorothioate bond

In one embodiment, a characteristic RNAi (e.g., dsRNA) herein comprises a first sequence of dsRNA selected from the group consisting of the sense sequences of any of the tables herein, and a second sequence selected from the group consisting of the corresponding antisense sequences of any of the tables herein. The corresponding antisense sequences are nucleotide sequences within the OSID family, such as OSC17. In those cases, when we refer to siRNA without a suffix (e.g., OSC 17), we mean dsRNA consisting of an antisense strand and a sense strand corresponding to that number (e.g., OSC17A paired with OSC17S or OSC17C- (n) paired with OSC17B- (n), where "n" is any number of the OSC17 family).

Unless otherwise specified, a compound provided herein may be enantiomerically pure, such as a single enantiomer or a single diastereomer, or a stereoisomeric mixture, such as a mixture of enantiomers, e.g., a racemic mixture of two enantiomers; or a mixture of two or more diastereomers. Conventional techniques for preparing/separating individual enantiomers include synthesis of precursors from suitable optical purity, asymmetric synthesis from achiral starting materials, or decomposition of mixtures of enantiomers (e.g. chiral chromatography, recrystallisation, decomposition), formation of diastereomeric salts, or derivatization into diastereomeric adducts followed by separation. It is understood that phosphorothioate groups represented by asterisks constitute stereocenters and that the presence of each such group in the sequence gives rise to two diastereomers. The number of such diastereomers in double stranded RNAi agents can be calculated by the formula 2n, where n represents the number of phosphorothioate groups in the sequence consisting of double stranded siRNA.

In some embodiments, the antisense strand (identified by "A" in the OS ID name) and/or sense strand (identified by "S" in the OS ID name) of the RNAi agent comprises or consists of a nucleobase sequence, e.g., "OSC17A-1" CAGUUGGUUUUUGUUCUUCAGUUC [ dT ] (SEQ ID NO: 17), and the nucleobase sequence may comprise at least one or more nucleotides that are modified nucleotides, and wherein SEQ ID NO:17 is located at positions 1-25 (5 '. Fwdarw.3') of the antisense strand and forms a duplex with the corresponding sense strand (identified as OSC 17S-1). In some embodiments, the antisense strand of the RNAi agent comprises or consists of a nucleobase sequence, e.g., CAGUUGCGCAGUUUCUUGUCAGUUC [ dT ] [ dT ] (SEQ ID NO: 17), wherein all or substantially all or 1, 2, 3,4, or 5 nucleotides are modified nucleotides (see, e.g., SEQ ID NO: 24), and wherein SEQ ID NO:124 is located at positions 1-27 (5 '. Fwdarw.3') of the antisense strand. For any of the antisense strands or sense strands disclosed herein, in some embodiments, the antisense strand of the RNAi agent comprises or consists of the sequence (5 '→3'), wherein x is a phosphorothioate linkage between deoxythymines [ dT ]; and/or wherein mC, mA, mG, mU is 2 '-O-methylcytidine, 2' -O-methyladenine, 2 '-O-methylguanosine, 2' -O-methyluridine, respectively; and/or wherein 2fA, 2fU, 2fG, 2fC are 2 '-fluoroadenine, 2' -fluorouridine, 2 '-fluoroguanosine, and 2' -fluorocytosine, respectively. Antisense targets on mRNA are identified by the same names, but without the "a" or "S" labels following the names. Antisense sequences having the same name, such as OSC17A-1 to OSC17A-18, bind to the same nucleotide target sequence.

The sequences shown in table 4 were transfected into HEK 293 (human embryonic kidney) and MDA-MB-435S (human melanoma) cell lines to determine their ability to reduce protein expression of LRP2 and CD320 genes/proteins. Both cell lines were chosen because of their relatively high levels of LRP2 expression (as noted in the human protein profile of the world wide web proteins. Org and the NCI-60 gene expression profile of discover. Nih. Gov/cellminer/so) and therefore the change in protein expression of LRP2 was readily detectable.

Referring now to FIGS. 3A-3B and 3D-3E, HEK293 and MDA-MB-231 cells were transfected with siRNA indicated at 20nM and incubated for 48 hours. Whole cell lysates were prepared and immunoblotted for CD320 and LRP2 protein levels. Protein levels were normalized to housekeeping control genes that were not affected by siRNA transfection. The graph shows fold-change in protein levels compared to the scrambled siRNA control (OSS 1). (mean-/+ SEM shown, n=3).

CD320 and LRP2 protein levels were determined by western blotting and quantified by Image Studio Software (LiCor corporation) relative to control proteins not affected by CD320 or LRP2 knockdown. To determine the efficacy of knockdown, the protein levels of CD320 (fig. 3A-3B) and LRP2 (fig. 3D-3E) on samples exposed to the siRNA sequences against mRNA of either gene were compared to the protein levels in untreated and scrambled controls (black and grey bars, respectively, in all figures of fig. 3). We found that the two siRNA sequences (OSC 17 and OSC 47) against CD320 almost completely abrogated expression of CD320 (circles in fig. 3A-3B). The siLRP2 sequence results in variable efficiency in reducing LRP2 protein. Both sequences (OSL 231 and OSL 245) consistently reduced LRP2 levels by more than 75% in both cell lines (circles in fig. 3B, 3E).

Referring now to fig. 6, lysates were prepared from transformed (HEK 293) and representative cancer cell lines and western blots were performed to determine LRP2 protein levels. The cancer cells selected have low levels of LRP2 expression. Results represent the mean + SEM of three independent lysates. The data indicate that the cancer cells screened have very low levels of LRP2 expression.

We transfected a panel of LRP2 and CD320 sirnas into cancer cell lines derived from various tissues and analyzed the levels of LRP2 protein and CD320 protein in the cell lines. Representative cell lines from prostate, breast and glioblastoma as well as normal fibroblasts were exposed to CD320 and LRP2 siRNA in an experimental setup similar to that for HEK293 and MDA-MB-435S cells. The results are shown in fig. 3C, 3F and 4.

Referring now to fig. 3C, 3F; and FIG. 4, MDA-MB-231LnCAP, MCF-7, and U251 cells are exposed to siRNA sequences to knock down CD320 (FIG. 3C and FIG. 4A-FIG. 4C) and LRP2 (FIG. 3F and FIG. 4D-FIG. 4F) in a similar manner as described for the data represented in FIG. 3A, FIG. 3B, FIG. 3D, and FIG. 3E. CD320 protein knockdown in fig. 3C and fig. 4A-4C was greater than 90% for all cell lines tested compared to untreated or scrambled controls. LRP2 knockdown was also achieved in all cell lines. However, the level of knockdown in LnCAP cells is lower compared to other cell lines, and the effective sequences can also be different (fig. 3F and 4D-4F).

Referring now to fig. 5, an experimental setup similar to that described in fig. 3 was employed. Additional prostate and brain cancer cell lines and normal fibroblasts were exposed to siRNA against CD 320. The level of CD320 was almost eliminated in DU-145 (prostate) cells, while the levels knocked down in a172 brain cells and normal fibroblasts were 21% -33% and 25% -28%, respectively (fig. 5A-5C).

From these studies we can conclude that in almost every cell line tested, both siRNAs against CD320 (OSC 17 and OSC 47) were very effective in knocking down CD320 protein levels (more than 80%). Although LRP2 is theoretically more difficult to knock down due to its size, we have identified two sirnas, OSL231 and OSL245, which consistently knock down LRP2 in most cell lines where we could detect LRP2.

Furthermore, the expression level of LRP2 protein in HEK293 cells is very high and is easy to detect by western blot. As measured by western blot, cancer cell lines have much lower LRP2 expression compared to HEK293 cells (fig. 6), and some cell lines may contain LRP2 below reliable detection levels.

Referring now to fig. 7, the effect of doxorubicin treatment on cell viability as measured by CTG assay is illustrated. A172 and HCC15 cells were plated in 96-well plates at 1200 cells/well. The next day, cells were treated with doxorubicin at the indicated concentrations. The viability of the cells was determined using CTG assay 4 days after the initial doxorubicin exposure. The lines indicate a non-linear fit of the data to calculate IC ₅₀ values. Instead of visually assessing the effect of CD320/LRP2 gene expression knockdown on cell proliferation (as shown in figure 2 for shRNA-mediated CD320/LRP2 knockdown), a functional assay was developed to quantify the effect of simultaneous knockdown of LRP2 and CD320 on cell viability by siRNA. A widely used assay for measuring cell viability is the Promega cell titer platform (CTG), which quantifies ATP levels in cells (viable cells produce ATP, and dead cells do not). After incubation of cells with CTG reagent, ATP levels can be measured indirectly from light production using a TECAN luminescence plate reader. As a first step, the toxicity of the known chemotherapeutic drug doxorubicin is determined on the cell line of interest. Doxorubicin was used as a positive control for cytotoxicity in our assay. Representative data from doxorubicin-exposed a172 brain cancer cells (fig. 7A) and HCC15 lung cancer cells (fig. 7B) are shown in fig. 7. From the data, IC ₅₀ for doxorubicin treatment on these cell lines was determined: 132nm for A172 cells and 167nm for HCC15 cells. Based on these findings, a larger screen was initiated to determine IC ₅₀ of doxorubicin in various cancer and non-cancer cell lines, and thus determine the dose of doxorubicin used when the cell lines were used in a viability assay to test simultaneous knockdown of CD320 and LRP 2. The results of the cell lines tested are summarized in table 8 (IC ₅₀ determination of doxorubicin).

To quantify the effect of knockdown CD320 and LRP2 on cell proliferation, cells were plated in 24-well plates. The next day, cells were transfected with CD320 and/or LRP 2. Cell lines may require repeated transfection and/or time for effective toxicity (cell line dependence). In this experimental setup, if some cell lines require re-infection for effective toxicity, there is room for re-infection. At the end of the study, cell growth of the cell lines was analyzed by CTG assay. A schematic of this experimental setup is presented in fig. 8.

TABLE 8

Cell lines were plated at 1000 to 4000 cells/well in 96-well plates and treated with doxorubicin the next day. CTG activity was measured 4 days after treatment. IC ₅₀ values were calculated by GRAPHPAD PRISM software. The results are tabulated in table 8.

These data show that doxorubicin works effectively on this CTG platform (i.e., doxorubicin kills cancer cells) and thus can be used as a positive control in an in vitro assay to compare the cytotoxic effects of siRNA knockdown of CD320 and LRP 2. In this latter assay, normal cells or cancer cells are transfected with individuals or combinations of siRNA sequences or control siRNA that specifically target CD320 or LRP2, similar to the experiments providing the data of fig. 3, 4 and 5. In figures 3, 4 and 5, protein levels are measured, but in an in vitro assay, cell viability is measured.

Referring now to fig. 8, an overview of a functional assay for screening (ds) siRNA for its effect on cell proliferation is illustrated. To quantify the effect of knockdown CD320 and LRP2 on cell proliferation, cells were plated in 24-well plates. The next day, cells were transfected with siRNA against CD320 and/or LRP 2. Cell lines may require repeated transfection and/or time for effective toxicity (cell line dependence). In this experimental setup, if some cell lines require re-infection for effective toxicity, there is room for re-infection. At the end of the study, cell growth of the cell lines was analyzed by CTG assay.

Referring now to fig. 10B, MDA-MB-231 triple negative breast cancer cells were plated in 24-well plates at 20000 cells/well. The cells were transfected with siRNA selected from OSC17, OSC47, OSL231 and OSL245 at 20nM for the next day. Cells were also transfected with a combination of two siRNAs (10 nM each) one targeting CD320 and the other targeting LRP2, the siRNA targeting CD30 being selected from the group of OSC17 and OSC47, and the siRNA targeting LRP2 being selected from the group of OSL231 and OSL245, each administered at 10 nM. As shown in table 9, cells were repeatedly transfected 4 times over the course of 11 days. On day 11, cells were analyzed for cell growth by CTG assay. The percent cell survival compared to the non-targeted control (OSS 2) is shown. The data presented are the mean of 6 experiments-/+ SEM.

Referring now to FIG. 11, MDA-MB-231 and DU-145 cells were transfected with 20nM negative control siRNA (OSS 2), 20nM CD 320-targeting siRNA (OSC 17) or 20nM LRP 2-targeting siRNA (OSL 245). Cells were also transfected with a combination of CD 320-targeting siRNA (OSC 17) and LRP 2-targeting siRNA (OSL 24) in a concentration range (2-20 nM), so the concentration of both sirnas was equal to 20nM of the total siRNA transfected, as shown in fig. 11. As shown in table 9, transfected cells were repeated and the percent cell survival is shown.

Referring now to FIG. 12, MDA-MB-231 breast cancer cells were transfected with 20nM negative control siRNA (OSS 2), 20nM CD320 targeting siRNA (OSC 17), or 20nM LRP2 targeting siRNA (OSL 245). Lysates were prepared daily within 5 days. Lysates were subjected to western blotting for CD320 protein level (fig. 12A) or LRP2 protein level (fig. 12B).

Referring now to fig. 9 and 10, data quantifying the effect of knockdown CD320 and LRP2 in various cell lines is shown. As shown, cell lines representing multiple types of cancer or normal fibroblasts were transfected with single or combination of siRNA against CD320 or LRP 2. Cells were transfected repeatedly for potent toxicity and then cell viability was determined by CTG assay as summarized in table 9. In our assay, doxorubicin-treated cells served as positive controls for cytotoxicity.

The data presented in fig. 9 and 10, along with the additional cell lines we screened, are summarized in table 9. These experiments show the broad applicability of siCD320,320 and siLRP2 toxicities in individual cancer types.

Referring now to FIG. 13, a schematic diagram of PEI and siRNA complexes is illustrated. PEI and siRNA were mixed together. Subsequently, a multi-complex (broadly, nanoparticle) of PEI siRNA complex is formed, which is able to enter the cell by endocytic or pinocytosis mechanism.

Referring now to fig. 14, sirna is a short RNA duplex, typically 16 to 30 nucleotides; the sequence of the siRNA is complementary to mRNA expressed in the cell. Exogenous siRNA duplex is introduced into cells by transfection methods. The siRNA duplex is unwound by RISC (RNA-induced silencing complex) complex, whereby the guide strand of the siRNA hybridizes to the mRNA molecule to which it is complementary. mRNA is degraded by the RISC/AGO complex, which has RNase cleavage activity. The end result is that the mRNA targeted by the siRNA is degraded and no protein encoded by the mRNA is produced. This results in a "knockdown" effect or reduced protein levels of the gene targeted by the siRNA compared to control treated cells.

Referring now to fig. 15, the effectiveness of INTERFERIN in delivering siRNA to cancer cells is illustrated. The siRNA indicated at 2nM was transfected into A172 and MDA-MB-435S cells according to the manufacturer' S protocol. Cell lysates were prepared 3 days after infection and analyzed for CD320 protein levels by western blotting. OSS1 and OSS2 were non-targeted siRNA controls. In this experiment, two sequences were tested. In contrast to OSS1, CD320 protein levels were knocked down to 9% to 18% for a172 cells and 26% to 48% for MDA-MB-435S cells. A more efficient knockdown of CD320 is observed when siRNA is delivered with other transfection reagents (e.g., RNAiMAX, viromer Blue) used in the previously described experiments, particularly against MDA-MB-435S cells. The Polyplus INTERFERin platform has been tested in our laboratory in vitro in principle verification experiments, whereby the platform is capable of delivering siRNA to target cells in vitro.

Referring now to fig. 16, treatment of breast cancer, prostate cancer and skin cancer cells with an amount of a CD320 receptor inhibitor or an LRP2 receptor inhibitor, or a combination of both, effective to inhibit proliferation of the cancer cells compared to control cells treated with control siRNA is illustrated. MDA-MB-231, DU145, lnCAP and MDA-MB-435S cells were plated in 24 well plates at 20000 cells/well. The following day, cells were transfected with either indicated siRNA or a scrambled control for knocking down CD320, LRP2 at 20 nM. For the combination of siRNAs, cells were treated with 10nM of each siRNA (20 nM total). As shown in table 9, cells were transfected repeatedly for the time periods indicated in table 9. Photographs of the indicated cells were taken at the end of the experiment.

TABLE 9 summary of functional siRNA data screening

Note that: the numbers represent percent survival compared to the negative control OSS 2.

A mouse-human tumor xenograft model was established using triple negative breast cancer cells (MDA-MB-231) injected into the flank of nude mice to test the efficacy of combined administration of OSC17 and OSL 245. Administration of the drug is performed by repeated administration within the drug concentration range using intratumoral iv, ip or dedicated administration routes. The dosing schedule is based on pilot studies to determine the tolerability of the delivery vehicle and drug and will be incorporated within the teachings of the art. Wherein the delivery platform is a nanoparticle, liposome, micelle, polymer, small molecule conjugate, aptamer, and antibody conjugate. Mixing techniques involving the elements of the above-described delivery systems are also known.

The manufacturing process involves the synthesis of two single stranded oligonucleotides of a duplex by conventional solid phase oligonucleotide synthesis. After purification, the two oligonucleotides were annealed to duplex.

In vivo is a cationic polymer delivery system that can bind negatively charged siRNA molecules to cationic polyamine polymers. Its use in xenograft models using MCF-7 (breast), MDA-MB-231 (breast) and a549 (lung) cell lines (both ip and intratumoral) has been reported. The delivery system is currently used in seven human clinical trials (table 10). The formulated siRNA was reported to be very stable.

TABLE 10 in vivo clinical trial use

Note that in the specification and claims, "about" or "approximately" means within twenty percent (20%) of the recited numerical quantity. Although the invention has been described in detail with particular reference to these embodiments, other embodiments may achieve the same results. For example, an antisense oligonucleotide complementary to a target mRNA may inhibit expression of a protein of interest even though the antisense oligonucleotide is not provided in the form of dsRNA and may not bind to RISC/AGO complex. Variations and modifications of the present invention will be obvious to those skilled in the art, and it is intended to cover in the appended claims all such modifications and equivalents. The entire disclosures of all references, applications, patents and publications cited above are incorporated herein by reference.

SEQUENCE LISTING

<110> BIOAFFINITY TECHNOLOGIES, INC.

<120> COMPOSITIONS AND METHODS FOR TREATING CANCER

<130> 32064-1035-PCT2

<140>

<141>

<150> 17/359,905

<151> 2021-06-28

<160> 1394

<170> PatentIn version 3.5

<210> 1

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 1

ucuuaucccu gcgcacgcgc att 23

<210> 2

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 2

ucucuuaucc cugcgcacgc gtt 23

<210> 3

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 3

augcuguccc cacagcggcg ctt 23

<210> 4

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 4

auccaaccgc cgcucaugcu gtt 23

<210> 5

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 5

uggaaagcgg gcucgcggcg gtt 23

<210> 6

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 6

aacuuggugg gugggcacga gtt 23

<210> 7

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 7

uggaacuugg ugggugggca ctt 23

<210> 8

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 8

acuggaacuu gguggguggg ctt 23

<210> 9

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 9

uaagccacug gugcggcacu gtt 23

<210> 10

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 10

acgcauaagc cacuggugcg gtt 23

<210> 11

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 11

uccaaguccc ugucgcagcg ctt 23

<210> 12

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 12

uccucaucgc ugccaucgcu gtt 23

<210> 13

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 13

ucacugacgc cggugcaggg gtt 23

<210> 14

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 14

uugucaguuc ccccagagca gtt 23

<210> 15

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 15

uucuugucag uucccccaga gtt 23

<210> 16

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 16

aguuucuugu caguuccccc att 23

<210> 17

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 17

caguugcgca guuucuuguc aguuctt 27

<210> 18

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 18

caguugcgca guuucuuguc aguuctt 27

<210> 19

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 19

caguugcgca guuucuuguc aguuctt 27

<210> 20

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 20

caguugcgca guuucuuguc aguuctt 27

<210> 21

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 21

caguugcgca guuucuuguc aguuc 25

<210> 22

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 22

caguugcgca guuucuuguc aguuc 25

<210> 23

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 23

caguugcgca guuucuuguc aguuctt 27

<210> 24

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 24

caguugcgca guuucuuguc aguuctt 27

<210> 25

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 25

caguugcgca guuucuuguc aguuc 25

<210> 26

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 26

caguugcgca guuucuuguc aguuctt 27

<210> 27

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 27

caguugcgca guuucuuguc aguuc 25

<210> 28

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 28

caguugcgca guuucuuguc aguuctt 27

<210> 29

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 29

caguugcgca guuucuuguc aguuc 25

<210> 30

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 30

caguugcgca guuucuuguc aguuctt 27

<210> 31

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 31

caguugcgca guuucuuguc aguuctt 27

<210> 32

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 32

caguugcgca guuucuuguc aguuctt 27

<210> 33

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 33

caguugcgca guuucuuguc agu 23

<210> 34

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 34

caguugcgca guuucuuguc agu 23

<210> 35

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 35

augcagucau cgcucagcgu gtt 23

<210> 36

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 36

aaugcaguca ucgcucagcg utt 23

<210> 37

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 37

uggaaugcag ucaucgcuca gtt 23

<210> 38

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 38

aguggaaugc agucaucgcu ctt 23

<210> 39

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 39

acagucuggg uggccgucgc att 23

<210> 40

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 40

auugguucca cagccgagcu ctt 23

<210> 41

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 41

ucucauuggu uccacagccg att 23

<210> 42

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 42

aucucauugg uuccacagcc gtt 23

<210> 43

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 43

aggaucucau ugguuccaca gtt 23

<210> 44

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 44

ugagagaggu gacacucucc att 23

<210> 45

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 45

ugguuguggc auuccugaga gtt 23

<210> 46

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 46

uggcauuccc gacagagggg att 23

<210> 47

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 47

aggauguggc auucccgaca gtt 23

<210> 48

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 48

uuccagacug gucuccggca gtt 23

<210> 49

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 49

auaaccccau aggcaguugg gtt 23

<210> 50

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 50

uugcacugag caccgcagca gtt 23

<210> 51

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 51

aaaaggagga ggguggcggu gtt 23

<210> 52

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 52

acaaaaggag gaggguggcg gtt 23

<210> 53

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 53

accaguaacc ccagugggcg gtt 23

<210> 54

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 54

uucauggcca ccaguaaccc ctt 23

<210> 55

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 55

acuccuucau ggccaccagu att 23

<210> 56

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 56

uucugacagc agcagggacu ctt 23

<210> 57

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 57

ucuguucuga cagcagcagg gtt 23

<210> 58

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 58

ucuucuguuc ugacagcagc att 23

<210> 59

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 59

aggucuucug uucugacagc att 23

<210> 60

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 60

uuguccucag ggcagcgagg utt 23

<210> 61

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 61

aagugcuugu ccucagggca gtt 23

<210> 62

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 62

uacccauccg caucacugcu ctt 23

<210> 63

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 63

ucucugaggg cuggugugcc ctt 23

<210> 64

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 64

aagagcucag gucucugagg gtt 23

<210> 65

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 65

aagagcucag gucucugagg gtt 23

<210> 66

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 66

aagagcucag gucucugagg gtt 23

<210> 67

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 67

aagagcucag gucucugagg gtt 23

<210> 68

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 68

aagagcucag gucucugagg g 21

<210> 69

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 69

aagagcucag gucucugagg g 21

<210> 70

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 70

aagagcucag gucucugagg gtt 23

<210> 71

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 71

aagagcucag gucucugagg gtt 23

<210> 72

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 72

aagagcucag gucucugagg g 21

<210> 73

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 73

aagagcucag gucucugagg gtt 23

<210> 74

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 74

aagagcucag gucucugagg g 21

<210> 75

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 75

aagagcucag gucucugagg gtt 23

<210> 76

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 76

aagagcucag gucucugagg g 21

<210> 77

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 77

aagagcucag gucucugagg g 21

<210> 78

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 78

aagagcucag gucucugagg gtt 23

<210> 79

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 79

aagagcucag gucucugagg gtt 23

<210> 80

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 80

aagagcucag gucucugagg gtt 23

<210> 81

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 81

aagagcucag gucucugagg g 21

<210> 82

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 82

aagagcucag gucucugagg gtt 23

<210> 83

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 83

agaagagcuc aggucucuga gtt 23

<210> 84

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 84

auagggagug uccagggacc ctt 23

<210> 85

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 85

uccauaggga guguccaggg att 23

<210> 86

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 86

aucuccauag ggagugucca gtt 23

<210> 87

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 87

ucaguucugg cuguggcagg utt 23

<210> 88

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 88

uucuaccccc ugggagcugc ctt 23

<210> 89

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 89

aagcacaggg ccguucuacc ctt 23

<210> 90

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 90

ugucuuaagc acagggccgu utt 23

<210> 91

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 91

agugucuuaa gcacagggcc gtt 23

<210> 92

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 92

uuuuuugagg augugaagca att 23

<210> 93

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 93

uuuuuuugag gaugugaagc att 23

<210> 94

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 94

ugcgcgugcg cagggauaag att 23

<210> 95

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 95

cgcgugcgca gggauaagag att 23

<210> 96

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 96

gcgccgcugu ggggacagca utt 23

<210> 97

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 97

cagcaugagc ggcgguugga utt 23

<210> 98

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 98

ccgccgcgag cccgcuuucc att 23

<210> 99

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 99

cucgugccca cccaccaagu utt 23

<210> 100

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 100

gugcccaccc accaaguucc att 23

<210> 101

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 101

gcccacccac caaguuccag utt 23

<210> 102

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 102

cagugccgca ccaguggcuu att 23

<210> 103

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 103

ccgcaccagu ggcuuaugcg utt 23

<210> 104

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 104

gcgcugcgac agggacuugg att 23

<210> 105

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 105

cagcgauggc agcgaugagg att 23

<210> 106

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 106

ccccugcacc ggcgucagug att 23

<210> 107

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 107

cugcucuggg ggaacugaca att 23

<210> 108

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 108

cucuggggga acugacaaga att 23

<210> 109

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 109

ugggggaacu gacaagaaac utt 23

<210> 110

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 110

gaacugacaa gaaacugcgc aacugtt 27

<210> 111

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 111

gaacugacaa gaaacugcgc aacugtt 27

<210> 112

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 112

gaacugacaa gaaacugcgc aacugtt 27

<210> 113

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 113

gaacugacaa gaaacugcgc aacug 25

<210> 114

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 114

gaacugacaa gaaacugcgc aacugtt 27

<210> 115

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 115

gaacugacaa gaaacugcgc aacug 25

<210> 116

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 116

gaacugacaa gaaacugcgc aacugtt 27

<210> 117

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 117

gaacugacaa gaaacugcgc aacugtt 27

<210> 118

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 118

gaacugacaa gaaacugcgc aacugtt 27

<210> 119

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 119

gaacugacaa gaaacugcgc aacug 25

<210> 120

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 120

gaacugacaa gaaacugcgc aacug 25

<210> 121

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 121

gaacugacaa gaaacugcgc aacugtt 27

<210> 122

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 122

gaacugacaa gaaacugcgc aacug 25

<210> 123

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 123

ugacaagaaa cugcgcaacu gtt 23

<210> 124

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 124

gaaacugcgc aacugtt 17

<210> 125

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 125

gaaacugcgc aacugtt 17

<210> 126

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 126

gaaacugcgc aacug 15

<210> 127

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 127

gaaacugcgc aacug 15

<210> 128

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 128

cacgcugagc gaugacugca utt 23

<210> 129

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 129

acgcugagcg augacugcau utt 23

<210> 130

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 130

cugagcgaug acugcauucc att 23

<210> 131

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 131

gagcgaugac ugcauuccac utt 23

<210> 132

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 132

ugcgacggcc acccagacug utt 23

<210> 133

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 133

gagcucggcu guggaaccaa utt 23

<210> 134

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 134

ucggcugugg aaccaaugag att 23

<210> 135

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 135

cggcugugga accaaugaga utt 23

<210> 136

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 136

cuguggaacc aaugagaucc utt 23

<210> 137

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 137

uggagagugu caccucucuc att 23

<210> 138

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 138

cucucaggaa ugccacaacc att 23

<210> 139

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 139

uccccucugu cgggaaugcc att 23

<210> 140

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 140

cugucgggaa ugccacaucc utt 23

<210> 141

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 141

cugccggaga ccagucugga att 23

<210> 142

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 142

cccaacugcc uaugggguua utt 23

<210> 143

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 143

cugcugcggu gcucagugca att 23

<210> 144

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 144

caccgccacc cuccuccuuu utt 23

<210> 145

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 145

ccgccacccu ccuccuuuug utt 23

<210> 146

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 146

ccgcccacug ggguuacugg utt 23

<210> 147

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 147

gggguuacug guggccauga att 23

<210> 148

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 148

uacugguggc caugaaggag utt 23

<210> 149

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 149

gagucccugc ugcugucaga att 23

<210> 150

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 150

ggcugcugcu gucagaacag att 23

<210> 151

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 151

ugcugcuguc agaacagaag att 23

<210> 152

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 152

ugcugucaga acagaagacc utt 23

<210> 153

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 153

accucgcugc ccugaggaca att 23

<210> 154

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 154

cugcccugag gacaagcacu utt 23

<210> 155

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 155

gagcagugau gcggaugggu att 23

<210> 156

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 156

gggcacacca gcccucagag att 23

<210> 157

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 157

cccucagaga ccugagcucu utt 23

<210> 158

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 158

cccucagaga ccugagcucu utt 23

<210> 159

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 159

cccucagaga ccugagcucu utt 23

<210> 160

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 160

cccucagaga ccugagcucu u 21

<210> 161

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 161

cccucagaga ccugagcucu utt 23

<210> 162

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 162

cccucagaga ccugagcucu u 21

<210> 163

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 163

cccucagaga ccugagcucu utt 23

<210> 164

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 164

cccucagaga ccugagcucu utt 23

<210> 165

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 165

cccucagaga ccugagcucu utt 23

<210> 166

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 166

cccucagaga ccugagcucu u 21

<210> 167

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 167

cccucagaga ccugagcucu u 21

<210> 168

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 168

cccucagaga ccugagcucu utt 23

<210> 169

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 169

cccucagaga ccugagcucu u 21

<210> 170

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 170

cccucagaga ccugagcucu utt 23

<210> 171

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 171

gagaccugag cucuutt 17

<210> 172

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 172

gagaccugag cucuutt 17

<210> 173

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 173

gagaccugag cucuu 15

<210> 174

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 174

gagaccugag cucuu 15

<210> 175

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 175

cccucagaga ccugagcucu utt 23

<210> 176

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 176

cucagagacc ugagcucuuc utt 23

<210> 177

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 177

gggucccugg acacucccua utt 23

<210> 178

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 178

ucccuggaca cucccuaugg att 23

<210> 179

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 179

cuggacacuc ccuauggaga utt 23

<210> 180

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 180

accugccaca gccagaacug att 23

<210> 181

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 181

ggcagcuccc aggggguaga att 23

<210> 182

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 182

ggguagaacg gcccugugcu utt 23

<210> 183

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 183

aacggcccug ugcuuaagac att 23

<210> 184

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 184

cggcccugug cuuaagacac utt 23

<210> 185

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 185

uugcuucaca uccucaaaaa att 23

<210> 186

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 186

ugcuucacau ccucaaaaaa att 23

<210> 187

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 187

uacuuuguga gcaaucuuga ctt 23

<210> 188

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 188

auucacuugg gauacacuga ctt 23

<210> 189

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 189

acaugaaaac ucauugugca att 23

<210> 190

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 190

ucuuuacagu caucuucucc att 23

<210> 191

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 191

uaucuuuaca gucaucuucu ctt 23

<210> 192

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 192

aacauuuaug aacaucauga gtt 23

<210> 193

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 193

ucacaaacuu uauaaaugga gtt 23

<210> 194

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 194

aucacaaacu uuauaaaugg att 23

<210> 195

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 195

auacuacagu auuuuccggu att 23

<210> 196

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 196

ucauacuaca guauuuuccg gtt 23

<210> 197

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 197

acaaauuccc cauaucuggc att 23

<210> 198

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 198

aagauauacc cuucuucaca gtt 23

<210> 199

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 199

uuagcuuugc aauacugucc att 23

<210> 200

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 200

aucauuagcu uugcaauacu gtt 23

<210> 201

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 201

aaaggaauca uuagcuuugc att 23

<210> 202

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 202

augaauauca ccaauuaaca att 23

<210> 203

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 203

aaaaaaccuu auuuugcacg gtt 23

<210> 204

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 204

ugaaaaaacc uuauuuugca ctt 23

<210> 205

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 205

aaugucaacu gaaaaaaccu utt 23

<210> 206

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 206

uaaugucaac ugaaaaaacc utt 23

<210> 207

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 207

uuaaaccauu aaugucaacu gtt 23

<210> 208

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 208

uauuuaaacc auuaauguca att 23

<210> 209

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 209

uagauuuuau uauuaaccca gtt 23

<210> 210

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 210

auagauuuua uuauuaaccc att 23

<210> 211

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 211

aaauuuacca uaucuaugcg gtt 23

<210> 212

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 212

aaguuuucag uuauaagggu att 23

<210> 213

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 213

aauaaauaac caacaguugg gtt 23

<210> 214

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 214

agaaaaauaa auaaccaaca gtt 23

<210> 215

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 215

auaucauauc cagaguuacc ctt 23

<210> 216

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 216

aguuucaaug uaaucaaacc gtt 23

<210> 217

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 217

uuacaguuuc aauguaauca att 23

<210> 218

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 218

auaaguuaca guuucaaugu att 23

<210> 219

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 219

ucuuuacacg gauugguagc att 23

<210> 220

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 220

aaaaucaauc ccgacaaaga att 23

<210> 221

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 221

ucugaaaaaa agauagugcu gtt 23

<210> 222

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 222

aucugaaaaa aagauagugc utt 23

<210> 223

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 223

aaaaaucaug uguuuugaca utt 23

<210> 224

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 224

uuugcuuaaa aaucaugugu utt 23

<210> 225

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 225

aacuuucaac auuuuccacc ctt 23

<210> 226

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 226

uugaaaucca aucaaaagcc att 23

<210> 227

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 227

uuugaaaucc aaucaaaagc ctt 23

<210> 228

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 228

uagagauucu uugaaaucca att 23

<210> 229

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 229

auagagauuc uuugaaaucc att 23

<210> 230

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 230

uuuaaauacu gaacuacugu gtt 23

<210> 231

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 231

uauuuaaaua cugaacuacu gtt 23

<210> 232

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 232

auagauaccc ggcaaaagga utt 23

<210> 233

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 233

aagaguagug uuuauuacag gtt 23

<210> 234

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 234

aucaaaauag gcaucuaccc att 23

<210> 235

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 235

ucaauuuuau caaaauaggc att 23

<210> 236

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 236

uaaaugcucu ccaaagaugg ctt 23

<210> 237

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 237

ucaaaugcag uauguaagca att 23

<210> 238

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 238

uucaaaugca guauguaagc att 23

<210> 239

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 239

ugauuacagg cguuagaacc att 23

<210> 240

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 240

uguuaucaug acaaucaucg att 23

<210> 241

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 241

uuaucacagg uguauugggu gtt 23

<210> 242

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 242

auuaucacag guguauuggg utt 23

<210> 243

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 243

aguucuuuga gauacacugg utt 23

<210> 244

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 244

ucgaauugca guucuuuuca utt 23

<210> 245

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 245

ucaauacauc gaugauuggg gtt 23

<210> 246

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 246

aacgauaggu caauacaucg att 23

<210> 247

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 247

acaaacgaua ggucaauaca utt 23

<210> 248

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 248

ucaaaaacac caucacaacg att 23

<210> 249

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 249

ucacauuccc agaaguucgg gtt 23

<210> 250

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 250

aucacauucc cagaaguucg gtt 23

<210> 251

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 251

ugaugaaggg caagucuugg gtt 23

<210> 252

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 252

agaaucauug gcaaguaaga att 23

<210> 253

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 253

uaucacauuc aucuaugucu utt 23

<210> 254

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 254

aauaucacau ucaucuaugu ctt 23

<210> 255

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 255

aacauguagc cuguaucaca ctt 23

<210> 256

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 256

ucacuuucua acauguagcc utt 23

<210> 257

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 257

aucacuuucu aacauguagc ctt 23

<210> 258

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 258

aauguaagaa ccauucucga ctt 23

<210> 259

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 259

uacaauguaa gaaccauucu ctt 23

<210> 260

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 260

aaaaucaaca gcuacaaugu att 23

<210> 261

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 261

auugaaucaa aaucaacagc utt 23

<210> 262

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 262

uaauugaauc aaaaucaaca gtt 23

<210> 263

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 263

aagauacgac cacuaauuga att 23

<210> 264

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 264

aguuucaguc aagaugaugc utt 23

<210> 265

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 265

aauaguuuca gucaagauga utt 23

<210> 266

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 266

uauugcaaua guuucaguca att 23

<210> 267

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 267

ucuauugcaa uaguuucagu ctt 23

<210> 268

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 268

aaucuauugc aauaguuuca gtt 23

<210> 269

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 269

auuuuggaga cuucaauugu utt 23

<210> 270

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 270

uuagguuuuu acuaaucagc att 23

<210> 271

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 271

ucauucuggg aucuaaugcu att 23

<210> 272

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 272

uucauucugg gaucuaaugc utt 23

<210> 273

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 273

aguagaugcu cauucauucu gtt 23

<210> 274

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 274

auuauaauca caaaagucca utt 23

<210> 275

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 275

uccauuauaa ucacaaaagu ctt 23

<210> 276

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 276

ugccguauaa ucaaaucact t 21

<210> 277

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 277

auauuauaca uuacaacuga ctt 23

<210> 278

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 278

auugaauauu auacauuaca att 23

<210> 279

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 279

aauuugguug uuucgaagga utt 23

<210> 280

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 280

acggaauuug guuguuucga att 23

<210> 281

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 281

uuacaguuau uaagaaaggu utt 23

<210> 282

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 282

uccaaaaauu auauguugcc utt 23

<210> 283

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 283

uuccaaaaau uauauguugc ctt 23

<210> 284

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 284

ucuaaaccau ucuguauccc utt 23

<210> 285

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 285

aucuaaacca uucuguaucc ctt 23

<210> 286

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 286

uucaacaucu aaaccauucu gtt 23

<210> 287

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 287

auuuucaacc caauagaugu att 23

<210> 288

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 288

uauagaagca aauacugucc utt 23

<210> 289

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 289

uagauauaga agcaaauacu gtt 23

<210> 290

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 290

uaaggccagg uucauagaag gtt 23

<210> 291

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 291

ucuugaaauc caaucuaagg ctt 23

<210> 292

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 292

auaaagguuu cuugaaaucc att 23

<210> 293

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 293

ucaaaaccuc gauugacuga gtt 23

<210> 294

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 294

uucuguaucu gauaucuccg utt 23

<210> 295

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 295

uuucuguauc ugauaucucc gtt 23

<210> 296

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 296

uuuuucugua ucugauaucu ctt 23

<210> 297

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 297

aucaauguuu uucuguaucu gtt 23

<210> 298

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 298

auaaaggaaa gaaucaugga ctt 23

<210> 299

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 299

aauaaaggaa agaaucaugg att 23

<210> 300

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 300

ucaguauaau aaaggaaaga att 23

<210> 301

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 301

uuucaaugac cucauacugu utt 23

<210> 302

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 302

auuuggaaca uuaucucuca att 23

<210> 303

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 303

agauuuggaa cauuaucucu ctt 23

<210> 304

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 304

ucagauuugg aacauuaucu ctt 23

<210> 305

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 305

uugcuacagc cauuugaggt t 21

<210> 306

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 306

augaaagagu uauauggaga gtt 23

<210> 307

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 307

acaaugaaag aguuauaugg att 23

<210> 308

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 308

ugaaacaaca augaaagagu utt 23

<210> 309

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 309

auugaaacaa caaugaaaga gtt 23

<210> 310

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 310

agcuaaagcc ucugauugca gtt 23

<210> 311

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 311

aagcuaaagc cucugauugc att 23

<210> 312

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 312

acaauuccaa gcuaaagccu ctt 23

<210> 313

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 313

ugacaauucc aagcuaaagc ctt 23

<210> 314

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 314

ugaaugaucu gacaauucca att 23

<210> 315

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 315

auguucauca gagaagaucc att 23

<210> 316

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 316

uauuccaugu gucacaaugu utt 23

<210> 317

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 317

acuucuauca guguuucaga att 23

<210> 318

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 318

uauugauccg cagaacuucu att 23

<210> 319

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 319

uguucuuggg aucuacaaca att 23

<210> 320

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 320

aaagaacgcu caaucuuugg utt 23

<210> 321

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 321

uaaacguagc caucacuucg gtt 23

<210> 322

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 322

aucuaaagaa ucaucaaccc att 23

<210> 323

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 323

uuauaucuaa agaaucauca att 23

<210> 324

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 324

auagaauuuu caaaaacagu gtt 23

<210> 325

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 325

ugauagaauu uucaaaaaca gtt 23

<210> 326

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 326

uuucaaauuc cuaucuaccc att 23

<210> 327

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 327

uuuucaaauu ccuaucuacc ctt 23

<210> 328

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 328

auauugucuc uuaucacugu gtt 23

<210> 329

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 329

ugauauuguc ucuuaucacu gtt 23

<210> 330

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 330

ugaaauggca caauucuugc ctt 23

<210> 331

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 331

uguugaaaug gcacaauucu utt 23

<210> 332

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 332

aauuuucugu ugaaauggca ctt 23

<210> 333

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 333

aaauuuucug uugaaauggc att 23

<210> 334

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 334

auuagacaag gcaaagauga gtt 23

<210> 335

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 335

acauuuauug uuuggaaagg utt 23

<210> 336

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 336

aucacuuaca cugucauagu ctt 23

<210> 337

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 337

uagauucuau cacuuacacu gtt 23

<210> 338

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 338

aguagauucu aucacuuaca ctt 23

<210> 339

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 339

uuuuguguga aguagauucu att 23

<210> 340

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 340

uaaauuuugu gugaaguaga utt 23

<210> 341

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 341

ucuaguaauc cagucaaagg ctt 23

<210> 342

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 342

aauucuucua guaauccagu ctt 23

<210> 343

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 343

uaaauucuuc uaguaaucca gtt 23

<210> 344

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 344

auaaauucuu cuaguaaucc att 23

<210> 345

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 345

auauacuggc cauagagagu ctt 23

<210> 346

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 346

uucuuugugu guacaaguca gtt 23

<210> 347

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 347

aauucuuugu guguacaagu ctt 23

<210> 348

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 348

ucgguaaauu cuuugugugu att 23

<210> 349

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 349

uguuacacug uuguuucugg utt 23

<210> 350

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 350

auuguuacac uguuguuucu gtt 23

<210> 351

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 351

aaacuguuca caaggauugu utt 23

<210> 352

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 352

acaucguuca ccauugucca ctt 23

<210> 353

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 353

uguuauugca cauaaacucc gtt 23

<210> 354

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 354

ucuguuauug cacauaaacu ctt 23

<210> 355

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 355

uuaugacauu uuguguaucc att 23

<210> 356

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 356

ugaauuauga cauuuugugu att 23

<210> 357

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 357

uuugaauuau gacauuuugu gtt 23

<210> 358

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 358

uacaaauauu ugaauuauga ctt 23

<210> 359

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 359

aaauaaacgc gaggaauaca att 23

<210> 360

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 360

aauaaguagg guuuucauca ctt 23

<210> 361

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 361

ucacaauacc aauguugagg att 23

<210> 362

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 362

uguuucuuga ucacaauacc att 23

<210> 363

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 363

aacaaucugu uucuugauca ctt 23

<210> 364

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 364

uuuacacaga gaaacucgga att 23

<210> 365

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 365

auuuacacag agaaacucgg att 23

<210> 366

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 366

uucugauucu caucguagcc gtt 23

<210> 367

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 367

auuuucagag caaguucucc utt 23

<210> 368

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 368

auaucuuugg gauacacagu ctt 23

<210> 369

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 369

agguaaacug auucuguugg ctt 23

<210> 370

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 370

auagaaacug guuaaggugu ctt 23

<210> 371

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 371

acaauagaaa cugguuaagg utt 23

<210> 372

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 372

ucaucaauau caacacaagu ctt 23

<210> 373

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 373

agauguagga gccuauuaca utt 23

<210> 374

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 374

ucgauguuac uguuuugccg gtt 23

<210> 375

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 375

uugcuaaaaa ugagauaggg utt 23

<210> 376

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 376

auuucucaaa uaguaacggu utt 23

<210> 377

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 377

aauuucucaa auaguaacgg utt 23

<210> 378

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 378

aaauuucuca aauaguaacg gtt 23

<210> 379

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 379

aguuaaauuu cucaaauagu att 23

<210> 380

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 380

aucuauaguu aaauuucuca att 23

<210> 381

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 381

uaaaaauagc caucuauagu utt 23

<210> 382

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 382

aucuaaugcc acaacauugu ctt 23

<210> 383

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 383

aauccaauac aaucucuucu ctt 23

<210> 384

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 384

acauucucuc aaugacuugc ctt 23

<210> 385

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 385

augauugucu ccuuguuugu ctt 23

<210> 386

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 386

auuaucacag acuuguuggu utt 23

<210> 387

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 387

uucaaaaaug guaauagcga att 23

<210> 388

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 388

ucuucaaaaa ugguaauagc gtt 23

<210> 389

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 389

auuuguuucc cuuuuccacu gtt 23

<210> 390

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 390

auuugaucca ucauauuugu utt 23

<210> 391

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 391

uauauggaug guacacaugg att 23

<210> 392

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 392

aaagaagacg gucuucauca gtt 23

<210> 393

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 393

ugaauucugu gaaguuguca ctt 23

<210> 394

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 394

acaaugucca cuuguacacu gtt 23

<210> 395

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 395

acacaauguc cacuuguaca ctt 23

<210> 396

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 396

uuuuugcauu cgaacauagu att 23

<210> 397

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 397

augguuuuug cauucgaaca utt 23

<210> 398

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 398

auacaaacau gguuuuugca utt 23

<210> 399

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 399

aucacauuuc caauauggcg gtt 23

<210> 400

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 400

ugaaguucuu caucugaacc att 23

<210> 401

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 401

auaaaugcag cgauuguugu ctt 23

<210> 402

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 402

auucuguaca agguuuaggg gtt 23

<210> 403

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 403

uauucuguac aagguuuagg gtt 23

<210> 404

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 404

auucauauuc uguacaaggu utt 23

<210> 405

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 405

uauucauauu cuguacaagg utt 23

<210> 406

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 406

uuauauucau auucuguaca att 23

<210> 407

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 407

uauugcaacc caguucaucg gtt 23

<210> 408

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 408

auauuuucag cacauguucu utt 23

<210> 409

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 409

uuaauugggu acaauuuugc utt 23

<210> 410

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 410

aaaaacauug guuucgaacc ctt 23

<210> 411

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 411

ugucaaaaac auugguuucg att 23

<210> 412

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 412

uucgaauucg gacauuguca gtt 23

<210> 413

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 413

auuauauuuu cgaauucgga ctt 23

<210> 414

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 414

agauuauauu uucgaauucg gtt 23

<210> 415

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 415

ucaucuugaa gauacucuga gtt 23

<210> 416

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 416

uauauuccuc aucuugaaga utt 23

<210> 417

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 417

uuugauagca ccaaaccuag agccctt 27

<210> 418

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 418

uuugauagca ccaaaccuag agccctt 27

<210> 419

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 419

uuugauagca ccaaaccuag agccctt 27

<210> 420

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 420

uuugauagca ccaaaccuag agccctt 27

<210> 421

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 421

uuugauagca ccaaaccuag agccc 25

<210> 422

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 422

uuugauagca ccaaaccuag agccc 25

<210> 423

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 423

uuugauagca ccaaaccuag agccctt 27

<210> 424

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 424

uuugauagca ccaaaccuag agccctt 27

<210> 425

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 425

uuugauagca ccaaaccuag agccc 25

<210> 426

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 426

uuugauagca ccaaaccuag agccctt 27

<210> 427

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 427

uuugauagca ccaaaccuag acccc 25

<210> 428

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 428

uuugauagca ccaaaccuag agccctt 27

<210> 429

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 429

uaucaaaccu cgauagcaac accgc 25

<210> 430

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 430

uuugauagca ccaaaccuag agccctt 27

<210> 431

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 431

uuugauagca ccaaaccuag agccctt 27

<210> 432

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 432

uuugauagca ccaaaccuag agccctt 27

<210> 433

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 433

uuugauagca ccaaaccuag agc 23

<210> 434

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 434

uuugauagca ccaaaccuag agc 23

<210> 435

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 435

ucaaaguugg ggauguaggc att 23

<210> 436

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 436

ucaguuucag gucaacuucc utt 23

<210> 437

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 437

uacguauuuc aguuucaggu ctt 23

<210> 438

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 438

uuacguauuu caguuucagg utt 23

<210> 439

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 439

aguuuagcca ccucaaugcg utt 23

<210> 440

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 440

aacauaagcc cuaguuuggg att 23

<210> 441

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 441

ucgauuuuag guuccuuucc ctt 23

<210> 442

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 442

ucgaaaacca ggauguugcg gtt 23

<210> 443

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 443

ucaaauaauc gauagaaagg ctt 23

<210> 444

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 444

uuguucaaau aaucgauaga att 23

<210> 445

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 445

uuaugguuuc aauaacgucc utt 23

<210> 446

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 446

uuuuaugguu ucaauaacgu ctt 23

<210> 447

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 447

auuuuauggu uucaauaacg utt 23

<210> 448

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 448

uuugcaauga cucuccuauc agucctt 27

<210> 449

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 449

uuugcaauga cucuccuauc agucctt 27

<210> 450

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 450

uuugcaauga cucuccuauc agucctt 27

<210> 451

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 451

uuugcaauga cucuccuauc agucctt 27

<210> 452

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 452

uuugcaauga cucuccuauc agucc 25

<210> 453

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 453

uuugcaauga cucuccuauc agucc 25

<210> 454

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 454

uuugcaauga cucuccuauc agucctt 27

<210> 455

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 455

uuugcaauga cucuccuauc agucctt 27

<210> 456

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 456

uuugcaauga cucuccuauc agucc 25

<210> 457

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 457

uuugcaauga cucuccuauc agucctt 27

<210> 458

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 458

uuugcaauga cucuccuauc acucc 25

<210> 459

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 459

uuugcaauga cucuccuauc agucctt 27

<210> 460

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 460

uauccuaagu cacacguuug acugc 25

<210> 461

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 461

uuugcaauga cucuccuauc agucctt 27

<210> 462

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 462

uuugcaauga cucuccuauc agucctt 27

<210> 463

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 463

uuugcaauga cucuccuauc agucctt 27

<210> 464

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 464

uuugcaauga cucuccuauc agu 23

<210> 465

<211> 23

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 465

uuugcaauga cucuccuauc agu 23

<210> 466

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 466

uagauaucca guauaacugg utt 23

<210> 467

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 467

uuuuguuucc auacuucucc ctt 23

<210> 468

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 468

auuuauuuug uuuccauacu utt 23

<210> 469

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 469

uauuguaucu gaguugauga att 23

<210> 470

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 470

ucaaaauagc aauuuccucc gtt 23

<210> 471

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 471

ucaucaaaau agcaauuucc utt 23

<210> 472

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 472

auuucacaau auuuuccggu gtt 23

<210> 473

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 473

uuugaaaacg ccauuucaca att 23

<210> 474

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 474

uucuauagug gaagaauccu gtt 23

<210> 475

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 475

auauccaugu uaagaucugc ctt 23

<210> 476

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 476

acaaagucuu cacucauugc ctt 23

<210> 477

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 477

uuauuaucca cauuuucaga utt 23

<210> 478

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 478

ucuuauuauc cacauuuuca gtt 23

<210> 479

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 479

uccauaauuc uuauuaucca ctt 23

<210> 480

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 480

uuccauaauu cuuauuaucc att 23

<210> 481

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 481

uuuucguuug aagagauucc att 23

<210> 482

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 482

uagauuuucg uuugaagaga utt 23

<210> 483

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 483

uuuagauuuu cguuugaaga gtt 23

<210> 484

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 484

uuguuuagau uuucguuuga att 23

<210> 485

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 485

uaguuuguuu agauuuucgu utt 23

<210> 486

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 486

uuucaaaguu gguaguuugu utt 23

<210> 487

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 487

auuggauuuu caaaguuggu att 23

<210> 488

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 488

auagauugga uuuucaaagu utt 23

<210> 489

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 489

uuaaaagugu cuucuguugc att 23

<210> 490

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 490

ucuuuaacaa gauuugcggu gtt 23

<210> 491

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 491

ucuucuuuaa caagauuugc gtt 23

<210> 492

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 492

ugguauagcu auacuucaga gtt 23

<210> 493

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 493

auuauucccu aaauagcugg utt 23

<210> 494

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 494

uaauuauucc cuaaauagcu gtt 23

<210> 495

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 495

auauaugugc aaaagugugu utt 23

<210> 496

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 496

aaauauaugu gcaaaagugu gtt 23

<210> 497

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 497

aacuuuuuuc aucuguuugu att 23

<210> 498

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 498

uaaaguacug aauguuaacu utt 23

<210> 499

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 499

uuuuuuucau aaaguacuga att 23

<210> 500

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 500

uauuuuuuuc auaaaguacu gtt 23

<210> 501

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 501

auuuguaaaa auaugagacg gtt 23

<210> 502

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 502

acauugugau aauuauuugu att 23

<210> 503

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 503

auacauauag uacauuguga utt 23

<210> 504

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 504

auauacauau aguacauugu gtt 23

<210> 505

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 505

aaagauauac auauaguaca utt 23

<210> 506

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 506

auuaccuuca gacaacuuca gtt 23

<210> 507

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 507

uauuuauagu auuaccuuca gtt 23

<210> 508

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 508

uaaucuuucc aaaauuuaca att 23

<210> 509

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 509

aguaacagga uaaucuuucc att 23

<210> 510

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 510

auucaguaac aggauaaucu utt 23

<210> 511

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 511

uagcaaauuc aguaacagga utt 23

<210> 512

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 512

uuagcaaauu caguaacagg att 23

<210> 513

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 513

ucuuuauuag caaauucagu att 23

<210> 514

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 514

aucauuuacu auaaugauca ctt 23

<210> 515

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 515

uucuuguugg aucauuuacu att 23

<210> 516

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 516

ucaauuccuu uucuuguugg att 23

<210> 517

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 517

auuuuauagg aaauaugagu gtt 23

<210> 518

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 518

uaauuuuaua ggaaauauga gtt 23

<210> 519

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 519

ugcuaaugug uaaaaaugga ctt 23

<210> 520

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 520

uugaacauua auuaagugcu att 23

<210> 521

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 521

auugaacauu aauuaagugc utt 23

<210> 522

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 522

auauugaaca uuaauuaagu gtt 23

<210> 523

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 523

aaauugacau guaauauuga att 23

<210> 524

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 524

aucaacauag ccauuaauca att 23

<210> 525

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 525

ucuauacaac acauaguggc ctt 23

<210> 526

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 526

augucuauac aacacauagu gtt 23

<210> 527

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 527

acugaauugc uuuuccuacc utt 23

<210> 528

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 528

aaauaaaaau guugucuugg ctt 23

<210> 529

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 529

aucacaaaua aaaauguugu ctt 23

<210> 530

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 530

aaugauaugg gauuuccuca utt 23

<210> 531

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 531

auuaaccaca aacucaaugc att 23

<210> 532

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 532

uuuaauuaac cacaaacuca att 23

<210> 533

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 533

uuugguuuca gaaauucagc utt 23

<210> 534

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 534

uuaugaagac acagauuugg utt 23

<210> 535

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 535

uuucauagaa acaaaaaccc att 23

<210> 536

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 536

augauauuuu cauagaaaca att 23

<210> 537

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 537

uauaaugaua uuuucauaga att 23

<210> 538

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 538

ugauuauaau gauauuuuca utt 23

<210> 539

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 539

auaaauagug auuauaauga utt 23

<210> 540

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 540

aaaagcuuaa uaagaauggu utt 23

<210> 541

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 541

aaaaagcuua auaagaaugg utt 23

<210> 542

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 542

uaaauguaca cauuuagcca ctt 23

<210> 543

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 543

auaaauguac acauuuagcc att 23

<210> 544

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 544

uauaaaugua cacauuuagc ctt 23

<210> 545

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 545

uucuaauaua aauguacaca utt 23

<210> 546

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 546

aagaauuaaa gaaaagaucu gtt 23

<210> 547

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 547

aauaagaauu aaagaaaaga utt 23

<210> 548

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 548

aaaccaauaa gaauuaaaga att 23

<210> 549

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 549

acuauaccca cuauuuaaga gtt 23

<210> 550

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 550

acaaaugugc aauauuagca ctt 23

<210> 551

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 551

aacaaaugug caauauuagc att 23

<210> 552

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 552

auguuucauu cauucaucca utt 23

<210> 553

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 553

aguaguauau guuucauuca utt 23

<210> 554

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 554

aaucaguagu auauguuuca utt 23

<210> 555

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 555

aaauaaucag uaguauaugu utt 23

<210> 556

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 556

aaucaaagua auuacaguca gtt 23

<210> 557

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 557

aucuaaucaa aguaauuaca gtt 23

<210> 558

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 558

uuauuuccag uuguuuaucu att 23

<210> 559

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 559

uuauuagaac uuuuucagca gtt 23

<210> 560

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 560

uuuauuagaa cuuuuucagc att 23

<210> 561

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 561

gucaagauug cucacaaagu att 23

<210> 562

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 562

gucaguguau cccaagugaa utt 23

<210> 563

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 563

uugcacaaug aguuuucaug utt 23

<210> 564

<211> 25

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 564

uggagaagau gacuguaaag auatt 25

<210> 565

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 565

gagaagauga cuguaaagau att 23

<210> 566

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 566

cucaugaugu ucauaaaugu utt 23

<210> 567

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 567

cuccauuuau aaaguuugug att 23

<210> 568

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 568

uccauuuaua aaguuuguga utt 23

<210> 569

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 569

uaccggaaaa uacuguagua utt 23

<210> 570

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 570

ccggaaaaua cuguaguaug att 23

<210> 571

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 571

ugccagauau ggggaauuug utt 23

<210> 572

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 572

cugugaagaa ggguauaucu utt 23

<210> 573

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 573

uggacaguau ugcaaagcua att 23

<210> 574

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 574

caguauugca aagcuaauga utt 23

<210> 575

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 575

ugcaaagcua augauuccuu utt 23

<210> 576

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 576

uuguuaauug gugauauuca utt 23

<210> 577

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 577

ccgugcaaaa uaagguuuuu utt 23

<210> 578

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 578

gugcaaaaua agguuuuuuc att 23

<210> 579

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 579

aagguuuuuu caguugacau utt 23

<210> 580

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 580

agguuuuuuc aguugacauu att 23

<210> 581

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 581

caguugacau uaaugguuua att 23

<210> 582

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 582

uugacauuaa ugguuuaaau att 23

<210> 583

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 583

cuggguuaau aauaaaaucu att 23

<210> 584

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 584

uggguuaaua auaaaaucua utt 23

<210> 585

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 585

ccgcauagau augguaaauu utt 23

<210> 586

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 586

uacccuuaua acugaaaacu utt 23

<210> 587

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 587

cccaacuguu gguuauuuau utt 23

<210> 588

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 588

cuguugguua uuuauuuuuc utt 23

<210> 589

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 589

ggguaacucu ggauaugaua utt 23

<210> 590

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 590

cgguuugauu acauugaaac utt 23

<210> 591

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 591

uugauuacau ugaaacugua att 23

<210> 592

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 592

uacauugaaa cuguaacuua utt 23

<210> 593

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 593

ugcuaccaau ccguguaaag att 23

<210> 594

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 594

uucuuugucg ggauugauuu utt 23

<210> 595

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 595

cagcacuauc uuuuuuucag att 23

<210> 596

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 596

agcacuaucu uuuuuucaga utt 23

<210> 597

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 597

augucaaaac acaugauuuu utt 23

<210> 598

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 598

aacacaugau uuuuaagcaa att 23

<210> 599

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 599

ggguggaaaa uguugaaagu utt 23

<210> 600

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 600

uggcuuuuga uuggauuuca att 23

<210> 601

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 601

ggcuuuugau uggauuucaa att 23

<210> 602

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 602

uuggauuuca aagaaucucu att 23

<210> 603

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 603

uggauuucaa agaaucucua utt 23

<210> 604

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 604

cacaguaguu caguauuuaa att 23

<210> 605

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 605

caguaguuca guauuuaaau att 23

<210> 606

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 606

auccuuuugc cggguaucua utt 23

<210> 607

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 607

ccccuguaau aaacacuacu ctt 23

<210> 608

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 608

uggguagaug ccuauuuuga utt 23

<210> 609

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 609

ugccuauuuu gauaaaauug att 23

<210> 610

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 610

gccaucuuug gagagcauuu att 23

<210> 611

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 611

uugcuuacau acugcauuug att 23

<210> 612

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 612

ugcuuacaua cugcauuuga att 23

<210> 613

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 613

ugguucuaac gccuguaauc att 23

<210> 614

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 614

ucgaugauug ucaugauaac att 23

<210> 615

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 615

cacccaauac accugugaua att 23

<210> 616

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 616

acccaauaca ccugugauaa utt 23

<210> 617

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 617

accaguguau cucaaagaac utt 23

<210> 618

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 618

augaaaagaa cugcaauucg att 23

<210> 619

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 619

ccccaaucau cgauguauug att 23

<210> 620

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 620

ucgauguauu gaccuaucgu utt 23

<210> 621

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 621

auguauugac cuaucguuug utt 23

<210> 622

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 622

ucguugugau gguguuuuug att 23

<210> 623

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 623

cccgaacuuc ugggaaugug att 23

<210> 624

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 624

ccgaacuucu gggaauguga utt 23

<210> 625

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 625

cccaagacuu gcccuucauc att 23

<210> 626

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 626

uucuuacuug ccaaugauuc utt 23

<210> 627

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 627

aagacauaga ugaaugugau att 23

<210> 628

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 628

gacauagaug aaugugauau utt 23

<210> 629

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 629

gugugauaca ggcuacaugu utt 23

<210> 630

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 630

aggcuacaug uuagaaagug att 23

<210> 631

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 631

ggcuacaugu uagaaaguga utt 23

<210> 632

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 632

gucgagaaug guucuuacau utt 23

<210> 633

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 633

gagaaugguu cuuacauugu att 23

<210> 634

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 634

uacauuguag cuguugauuu utt 23

<210> 635

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 635

agcuguugau uuugauucaa utt 23

<210> 636

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 636

cuguugauuu ugauucaauu att 23

<210> 637

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 637

uucaauuagu ggucguaucu utt 23

<210> 638

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 638

agcaucaucu ugacugaaac utt 23

<210> 639

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 639

aucaucuuga cugaaacuau utt 23

<210> 640

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 640

uugacugaaa cuauugcaau att 23

<210> 641

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 641

gacugaaacu auugcaauag att 23

<210> 642

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 642

cugaaacuau ugcaauagau utt 23

<210> 643

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 643

aacaauugaa gucuccaaaa utt 23

<210> 644

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 644

ugcugauuag uaaaaaccua att 23

<210> 645

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 645

uagcauuaga ucccagaaug att 23

<210> 646

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 646

agcauuagau cccagaauga att 23

<210> 647

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 647

cagaaugaau gagcaucuac utt 23

<210> 648

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 648

auggacuuuu gugauuauaa utt 23

<210> 649

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 649

gacuuuugug auuauaaugg att 23

<210> 650

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 650

gugugauuug auuauacggc att 23

<210> 651

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 651

gucaguugua auguauaaua utt 23

<210> 652

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 652

uuguaaugua uaauauucaa utt 23

<210> 653

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 653

auccuucgaa acaaccaaau utt 23

<210> 654

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 654

uucgaaacaa ccaaauuccg utt 23

<210> 655

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 655

aaccuuucuu aauaacugua att 23

<210> 656

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 656

aggcaacaua uaauuuuugg att 23

<210> 657

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 657

ggcaacauau aauuuuugga att 23

<210> 658

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 658

agggauacag aaugguuuag att 23

<210> 659

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 659

gggauacaga augguuuaga utt 23

<210> 660

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 660

cagaaugguu uagauguuga att 23

<210> 661

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 661

uacaucuauu ggguugaaaa utt 23

<210> 662

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 662

aggacaguau uugcuucuau att 23

<210> 663

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 663

caguauuugc uucuauaucu att 23

<210> 664

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 664

ccuucuauga accuggccut t 21

<210> 665

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 665

gccuuagauu ggauuucaag att 23

<210> 666

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 666

uggauuucaa gaaaccuuua utt 23

<210> 667

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 667

cucagucaau cgagguuuug att 23

<210> 668

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 668

acggagauau cagauacaga att 23

<210> 669

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 669

cggagauauc agauacagaa att 23

<210> 670

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 670

gagauaucag auacagaaaa att 23

<210> 671

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 671

cagauacaga aaaacauuga utt 23

<210> 672

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 672

guccaugauu cuuuccuuua utt 23

<210> 673

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 673

uccaugauuc uuuccuuuau utt 23

<210> 674

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 674

uucuuuccuu uauuauacug att 23

<210> 675

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 675

aacaguauga ggucauugaa att 23

<210> 676

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 676

uugagagaua auguuccaaa utt 23

<210> 677

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 677

gagagauaau guuccaaauc utt 23

<210> 678

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 678

gagauaaugu uccaaaucug att 23

<210> 679

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 679

ccucaaaugg cuguagcaat t 21

<210> 680

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 680

cucuccauau aacucuuuca utt 23

<210> 681

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 681

uccauauaac ucuuucauug utt 23

<210> 682

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 682

aacucuuuca uuguuguuuc att 23

<210> 683

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 683

cucuuucauu guuguuucaa utt 23

<210> 684

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 684

cugcaaucag aggcuuuagc utt 23

<210> 685

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 685

ugcaaucaga ggcuuuagcu utt 23

<210> 686

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 686

gaggcuuuag cuuggaauug utt 23

<210> 687

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 687

ggcuuuagcu uggaauuguc att 23

<210> 688

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 688

uuggaauugu cagaucauuc att 23

<210> 689

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 689

uggaucuucu cugaugaaca utt 23

<210> 690

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 690

aacauuguga cacauggaau att 23

<210> 691

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 691

uucugaaaca cugauagaag utt 23

<210> 692

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 692

uagaaguucu gcggaucaau att 23

<210> 693

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 693

uuguuguaga ucccaagaac att 23

<210> 694

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 694

accaaagauu gagcguucuu utt 23

<210> 695

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 695

ccgaagugau ggcuacguuu att 23

<210> 696

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 696

uggguugaug auucuuuaga utt 23

<210> 697

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 697

uugaugauuc uuuagauaua att 23

<210> 698

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 698

cacuguuuuu gaaaauucua utt 23

<210> 699

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 699

cuguuuuuga aaauucuauc att 23

<210> 700

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 700

uggguagaua ggaauuugaa att 23

<210> 701

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 701

ggguagauag gaauuugaaa att 23

<210> 702

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 702

cacagugaua agagacaaua utt 23

<210> 703

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 703

cagugauaag agacaauauc att 23

<210> 704

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 704

ggcaagaauu gugccauuuc att 23

<210> 705

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 705

aagaauugug ccauuucaac att 23

<210> 706

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 706

gugccauuuc aacagaaaau utt 23

<210> 707

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 707

ugccauuuca acagaaaauu utt 23

<210> 708

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 708

cucaucuuug ccuugucuaa utt 23

<210> 709

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 709

accuuuccaa acaauaaaug utt 23

<210> 710

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 710

gacuaugaca guguaaguga utt 23

<210> 711

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 711

caguguaagu gauagaaucu att 23

<210> 712

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 712

guguaaguga uagaaucuac utt 23

<210> 713

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 713

uagaaucuac uucacacaaa att 23

<210> 714

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 714

aucuacuuca cacaaaauuu att 23

<210> 715

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 715

gccuuugacu ggauuacuag att 23

<210> 716

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 716

gacuggauua cuagaagaau utt 23

<210> 717

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 717

cuggauuacu agaagaauuu att 23

<210> 718

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 718

uggauuacua gaagaauuua utt 23

<210> 719

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 719

gacucucuau ggccaguaua utt 23

<210> 720

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 720

cugacuugua cacacaaaga att 23

<210> 721

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 721

gacuuguaca cacaaagaau utt 23

<210> 722

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 722

uacacacaaa gaauuuaccg att 23

<210> 723

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 723

accagaaaca acaguguaac att 23

<210> 724

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 724

cagaaacaac aguguaacaa utt 23

<210> 725

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 725

aacaauccuu gugaacaguu utt 23

<210> 726

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 726

guggacaaug gugaacgaug utt 23

<210> 727

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 727

cggaguuuau gugcaauaac att 23

<210> 728

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 728

gaguuuaugu gcaauaacag att 23

<210> 729

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 729

uggauacaca aaaugucaua att 23

<210> 730

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 730

uacacaaaau gucauaauuc att 23

<210> 731

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 731

cacaaaaugu cauaauucaa att 23

<210> 732

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 732

gucauaauuc aaauauuugu att 23

<210> 733

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 733

uuguauuccu cgcguuuauu utt 23

<210> 734

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 734

gugaugaaaa cccuacuuau utt 23

<210> 735

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 735

uccucaacau ugguauugug att 23

<210> 736

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 736

ugguauugug aucaagaaac att 23

<210> 737

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 737

gugaucaaga aacagauugu utt 23

<210> 738

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 738

uuccgaguuu cucuguguaa att 23

<210> 739

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 739

uccgaguuuc ucuguguaaa utt 23

<210> 740

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 740

cggcuacgau gagaaucaga att 23

<210> 741

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 741

aggagaacuu gcucugaaaa utt 23

<210> 742

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 742

gacuguguau cccaaagaua utt 23

<210> 743

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 743

gccaacagaa ucaguuuacc utt 23

<210> 744

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 744

gacaccuuaa ccaguuucua utt 23

<210> 745

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 745

accuuaacca guuucuauug utt 23

<210> 746

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 746

gacuuguguu gauauugaug att 23

<210> 747

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 747

auguaauagg cuccuacauc utt 23

<210> 748

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 748

ccggcaaaac aguaacaucg att 23

<210> 749

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 749

acccuaucuc auuuuuagca att 23

<210> 750

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 750

aaccguuacu auuugagaaa utt 23

<210> 751

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 751

accguuacua uuugagaaau utt 23

<210> 752

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 752

ccguuacuau uugagaaauu utt 23

<210> 753

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 753

uacuauuuga gaaauuuaac utt 23

<210> 754

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 754

uugagaaauu uaacuauaga utt 23

<210> 755

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 755

aacuauagau ggcuauuuuu att 23

<210> 756

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 756

gacaauguug uggcauuaga utt 23

<210> 757

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 757

gagaagagau uguauuggau utt 23

<210> 758

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 758

ggcaagucau ugagagaaug utt 23

<210> 759

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 759

gacaaacaag gagacaauca utt 23

<210> 760

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 760

aaccaacaag ucugugauaa utt 23

<210> 761

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 761

uucgcuauua ccauuuuuga att 23

<210> 762

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 762

cgcuauuacc auuuuugaag att 23

<210> 763

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 763

caguggaaaa gggaaacaaa utt 23

<210> 764

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 764

aacaaauaug auggaucaaa utt 23

<210> 765

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 765

uccaugugua ccauccauau att 23

<210> 766

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 766

cugaugaaga ccgucuucuu utt 23

<210> 767

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 767

gugacaacuu cacagaauuc att 23

<210> 768

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 768

cgguguacaa guggacauug utt 23

<210> 769

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 769

guguacaagu ggacauugug utt 23

<210> 770

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 770

uacuauguuc gaaugcaaaa att 23

<210> 771

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 771

auguucgaau gcaaaaacca utt 23

<210> 772

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 772

augcaaaaac cauguuugua utt 23

<210> 773

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 773

ccgccauauu ggaaauguga utt 23

<210> 774

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 774

ugguucagau gaagaacuuc att 23

<210> 775

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 775

gacaacaauc gcugcauuua utt 23

<210> 776

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 776

ccccuaaacc uuguacagaa utt 23

<210> 777

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 777

cccuaaaccu uguacagaau att 23

<210> 778

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 778

aaccuuguac agaauaugaa utt 23

<210> 779

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 779

accuuguaca gaauaugaau att 23

<210> 780

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 780

uuguacagaa uaugaauaua att 23

<210> 781

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 781

ccgaugaacu ggguugcaau att 23

<210> 782

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 782

aagaacaugu gcugaaaaua utt 23

<210> 783

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 783

agcaaaauug uacccaauua att 23

<210> 784

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 784

ggguucgaaa ccaauguuuu utt 23

<210> 785

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 785

ucgaaaccaa uguuuuugac att 23

<210> 786

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 786

cugacaaugu ccgaauucga att 23

<210> 787

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 787

guccgaauuc gaaaauauaa utt 23

<210> 788

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 788

ccgaauucga aaauauaauc utt 23

<210> 789

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 789

cucagaguau cuucaagaug att 23

<210> 790

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 790

aucuucaaga ugaggaauau att 23

<210> 791

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 791

gggcucuagg uuuggugcua ucaaatt 27

<210> 792

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 792

gggcucuagg uuuggugcua ucaaatt 27

<210> 793

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 793

gggcucuagg uuuggugcua ucaaatt 27

<210> 794

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 794

gggcucuagg uuuggugcua ucaaa 25

<210> 795

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 795

gggcucuagg uuuggugcua ucaaatt 27

<210> 796

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 796

gggcucuagg uuuggugcua ucaaa 25

<210> 797

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 797

gggcucuagg uuuggugcua ucaaatt 27

<210> 798

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 798

gggcucuagg uuuggugcua ucaaatt 27

<210> 799

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 799

gggcucuagg uuuggugcua ucaaatt 27

<210> 800

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 800

gggcucuagg uuuggugcua ucaaa 25

<210> 801

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 801

gggcucuagg uuuggugcua ucaaa 25

<210> 802

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 802

gggcucuagg uuuggugcua ucaaatt 27

<210> 803

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 803

gggcucuagg uuuggugcua ucaaa 25

<210> 804

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 804

ucuagguuug gugcuaucaa att 23

<210> 805

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 805

uuuggugcua ucaaatt 17

<210> 806

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 806

uuuggugcua ucaaatt 17

<210> 807

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 807

uuuggugcua ucaaa 15

<210> 808

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 808

uuuggugcua ucaaa 15

<210> 809

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 809

ugccuacauc cccaacuuug att 23

<210> 810

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 810

aggaaguuga ccugaaacug att 23

<210> 811

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 811

gaccugaaac ugaaauacgu att 23

<210> 812

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 812

accugaaacu gaaauacgua att 23

<210> 813

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 813

acgcauugag guggcuaaac utt 23

<210> 814

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 814

ucccaaacua gggcuuaugu utt 23

<210> 815

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 815

gggaaaggaa ccuaaaaucg att 23

<210> 816

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 816

ccgcaacauc cugguuuucg att 23

<210> 817

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 817

gccuuucuau cgauuauuug att 23

<210> 818

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 818

uucuaucgau uauuugaaca att 23

<210> 819

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 819

aggacguuau ugaaaccaua att 23

<210> 820

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 820

gacguuauug aaaccauaaa att 23

<210> 821

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 821

acguuauuga aaccauaaaa utt 23

<210> 822

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 822

ggacugauag gagagucauu gcaaatt 27

<210> 823

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 823

ggacugauag gagagucauu gcaaatt 27

<210> 824

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 824

ggacugauag gagagucauu gcaaatt 27

<210> 825

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 825

ggacugauag gagagucauu gcaaa 25

<210> 826

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 826

ggacugauag gagagucauu gcaaatt 27

<210> 827

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 827

ggacugauag gagagucauu gcaaa 25

<210> 828

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 828

ggacugauag gagagucauu gcaaatt 27

<210> 829

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 829

ggacugauag gagagucauu gcaaatt 27

<210> 830

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 830

ggacugauag gagagucauu gcaaatt 27

<210> 831

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 831

ggacugauag gagagucauu gcaaa 25

<210> 832

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 832

ggacugauag gagagucauu gcaaa 25

<210> 833

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 833

ggacugauag gagagucauu gcaaatt 27

<210> 834

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 834

ggacugauag gagagucauu gcaaa 25

<210> 835

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 835

ugauaggaga gucauugcaa att 23

<210> 836

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 836

gagagucauu gcaaatt 17

<210> 837

<211> 17

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 837

gagagucauu gcaaatt 17

<210> 838

<211> 15

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 838

gagagucauu gcaaa 15

<210> 839

<400> 839

000

<210> 840

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 840

accaguuaua cuggauaucu att 23

<210> 841

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 841

gggagaagua uggaaacaaa att 23

<210> 842

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 842

aaguauggaa acaaaauaaa utt 23

<210> 843

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 843

uucaucaacu cagauacaau att 23

<210> 844

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 844

cggaggaaau ugcuauuuug att 23

<210> 845

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 845

aggaaauugc uauuuugaug att 23

<210> 846

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 846

caccggaaaa uauugugaaa utt 23

<210> 847

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 847

uugugaaaug gcguuuucaa att 23

<210> 848

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 848

caggauucuu ccacuauaga att 23

<210> 849

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 849

ggcagaucuu aacauggaua utt 23

<210> 850

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 850

ggcaaugagu gaagacuuug utt 23

<210> 851

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 851

aucugaaaau guggauaaua att 23

<210> 852

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 852

cugaaaaugu ggauaauaag att 23

<210> 853

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 853

guggauaaua agaauuaugg att 23

<210> 854

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 854

uggauaauaa gaauuaugga att 23

<210> 855

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 855

uggaaucucu ucaaacgaaa att 23

<210> 856

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 856

aucucuucaa acgaaaaucu att 23

<210> 857

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 857

cucuucaaac gaaaaucuaa att 23

<210> 858

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 858

uucaaacgaa aaucuaaaca att 23

<210> 859

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 859

aacgaaaauc uaaacaaacu att 23

<210> 860

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 860

aacaaacuac caacuuugaa att 23

<210> 861

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 861

uaccaacuuu gaaaauccaa utt 23

<210> 862

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 862

aacuuugaaa auccaaucua utt 23

<210> 863

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 863

ugcaacagaa gacacuuuua att 23

<210> 864

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 864

caccgcaaau cuuguuaaag att 23

<210> 865

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 865

cgcaaaucuu guuaaagaag att 23

<210> 866

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 866

cucugaagua uagcuauacc att 23

<210> 867

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 867

accagcuauu uagggaauaa utt 23

<210> 868

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 868

cagcuauuua gggaauaauu att 23

<210> 869

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 869

aacacacuuu ugcacauaua utt 23

<210> 870

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 870

cacacuuuug cacauauauu utt 23

<210> 871

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 871

uacaaacaga ugaaaaaagu utt 23

<210> 872

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 872

aaguuaacau ucaguacuuu att 23

<210> 873

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 873

uucaguacuu uaugaaaaaa att 23

<210> 874

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 874

caguacuuua ugaaaaaaau att 23

<210> 875

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 875

ccgucucaua uuuuuacaaa utt 23

<210> 876

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 876

uacaaauaau uaucacaaug utt 23

<210> 877

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 877

aucacaaugu acuauaugua utt 23

<210> 878

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 878

cacaauguac uauauguaua utt 23

<210> 879

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 879

auguacuaua uguauaucuu utt 23

<210> 880

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 880

cugaaguugu cugaagguaa utt 23

<210> 881

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 881

cugaagguaa uacuauaaau att 23

<210> 882

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 882

uuguaaauuu uggaaagauu att 23

<210> 883

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 883

uggaaagauu auccuguuac utt 23

<210> 884

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 884

aagauuaucc uguuacugaa utt 23

<210> 885

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 885

auccuguuac ugaauuugcu att 23

<210> 886

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 886

uccuguuacu gaauuugcua att 23

<210> 887

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 887

uacugaauuu gcuaauaaag att 23

<210> 888

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 888

gugaucauua uaguaaauga utt 23

<210> 889

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 889

uaguaaauga uccaacaaga att 23

<210> 890

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 890

uccaacaaga aaaggaauug att 23

<210> 891

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 891

cacucauauu uccuauaaaa utt 23

<210> 892

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 892

cucauauuuc cuauaaaauu att 23

<210> 893

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 893

guccauuuuu acacauuagc att 23

<210> 894

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 894

uagcacuuaa uuaauguuca att 23

<210> 895

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 895

agcacuuaau uaauguucaa utt 23

<210> 896

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 896

cacuuaauua auguucaaua utt 23

<210> 897

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 897

uucaauauua caugucaauu utt 23

<210> 898

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 898

uugauuaaug gcuauguuga utt 23

<210> 899

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 899

ggccacuaug uguuguauag att 23

<210> 900

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 900

cacuaugugu uguauagaca utt 23

<210> 901

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 901

agguaggaaa agcaauucag utt 23

<210> 902

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 902

gccaagacaa cauuuuuauu utt 23

<210> 903

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 903

gacaacauuu uuauuuguga utt 23

<210> 904

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 904

augaggaaau cccauaucau utt 23

<210> 905

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 905

ugcauugagu uugugguuaa utt 23

<210> 906

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 906

uugaguuugu gguuaauuaa att 23

<210> 907

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 907

agcugaauuu cugaaaccaa att 23

<210> 908

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 908

accaaaucug ugucuucaua att 23

<210> 909

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 909

uggguuuuug uuucuaugaa att 23

<210> 910

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 910

uuguuucuau gaaaauauca utt 23

<210> 911

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 911

uucuaugaaa auaucauuau att 23

<210> 912

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 912

augaaaauau cauuauaauc att 23

<210> 913

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 913

aucauuauaa ucacuauuua utt 23

<210> 914

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 914

aaccauucuu auuaagcuuu utt 23

<210> 915

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 915

accauucuua uuaagcuuuu utt 23

<210> 916

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 916

guggcuaaau guguacauuu att 23

<210> 917

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 917

uggcuaaaug uguacauuua utt 23

<210> 918

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 918

ggcuaaaugu guacauuuau att 23

<210> 919

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 919

auguguacau uuauauuaga att 23

<210> 920

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 920

cagaucuuuu cuuuaauucu utt 23

<210> 921

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 921

aucuuuucuu uaauucuuau utt 23

<210> 922

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 922

uucuuuaauu cuuauugguu utt 23

<210> 923

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 923

cucuuaaaua guggguauag utt 23

<210> 924

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 924

gugcuaauau ugcacauuug utt 23

<210> 925

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 925

ugcuaauauu gcacauuugu utt 23

<210> 926

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 926

auggaugaau gaaugaaaca utt 23

<210> 927

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 927

augaaugaaa cauauacuac utt 23

<210> 928

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 928

augaaacaua uacuacugau utt 23

<210> 929

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 929

aacauauacu acugauuauu utt 23

<210> 930

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 930

cugacuguaa uuacuuugau utt 23

<210> 931

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 931

cuguaauuac uuugauuaga utt 23

<210> 932

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 932

uagauaaaca acuggaaaua att 23

<210> 933

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 933

cugcugaaaa aguucuaaua att 23

<210> 934

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 934

ugcugaaaaa guucuaauaa att 23

<210> 935

<211> 1283

<212> DNA

<213> Homo sapiens

<400> 935

gtgcgcgtgc gcagggataa gagagcggtc tggacagcgc gtggccggcg ccgctgtggg 60

gacagcatga gcggcggttg gatggcgcag gttggagcgt ggcgaacagg ggctctgggc 120

ctggcgctgc tgctgctgct cggcctcgga ctaggcctgg aggccgccgc gagcccgctt 180

tccaccccga cctctgccca ggccgcaggc cccagctcag gctcgtgccc acccaccaag 240

ttccagtgcc gcaccagtgg cttatgcgtg cccctcacct ggcgctgcga cagggacttg 300

gactgcagcg atggcagcga tgaggaggag tgcaggattg agccatgtac ccagaaaggg 360

caatgcccac cgccccctgg cctcccctgc ccctgcaccg gcgtcagtga ctgctctggg 420

ggaactgaca agaaactgcg caactgcagc cgcctggcct gcctagcagg cgagctccgt 480

tgcacgctga gcgatgactg cattccactc acgtggcgct gcgacggcca cccagactgt 540

cccgactcca gcgacgagct cggctgtgga accaatgaga tcctcccgga aggggatgcc 600

acaaccatgg ggccccctgt gaccctggag agtgtcacct ctctcaggaa tgccacaacc 660

atggggcccc ctgtgaccct ggagagtgtc ccctctgtcg ggaatgccac atcctcctct 720

gccggagacc agtctggaag cccaactgcc tatggggtta ttgcagctgc tgcggtgctc 780

agtgcaagcc tggtcaccgc caccctcctc cttttgtcct ggctccgagc ccaggagcgc 840

ctccgcccac tggggttact ggtggccatg aaggagtccc tgctgctgtc agaacagaag 900

acctcgctgc cctgaggaca agcacttgcc accaccgtca ctcagccctg ggcgtagccg 960

gacaggagga gagcagtgat gcggatgggt acccgggcac accagccctc agagacctga 1020

gctcttctgg ccacgtggaa cctcgaaccc gagctcctgc agaagtggcc ctggagattg 1080

agggtccctg gacactccct atggagatcc ggggagctag gatggggaac ctgccacagc 1140

cagaactgag gggctggccc caggcagctc ccagggggta gaacggccct gtgcttaaga 1200

cactcctgct gccccgtctg agggtggcga ttaaagttgc ttcacatcct caaaaaaaaa 1260

aaaaaaaaaa aaaaaaaaaa aaa 1283

<210> 936

<211> 282

<212> PRT

<213> Homo sapiens

<400> 936

Met Ser Gly Gly Trp Met Ala Gln Val Gly Ala Trp Arg Thr Gly Ala

1 5 10 15

Leu Gly Leu Ala Leu Leu Leu Leu Leu Gly Leu Gly Leu Gly Leu Glu

20 25 30

Ala Ala Ala Ser Pro Leu Ser Thr Pro Thr Ser Ala Gln Ala Ala Gly

35 40 45

Pro Ser Ser Gly Ser Cys Pro Pro Thr Lys Phe Gln Cys Arg Thr Ser

50 55 60

Gly Leu Cys Val Pro Leu Thr Trp Arg Cys Asp Arg Asp Leu Asp Cys

65 70 75 80

Ser Asp Gly Ser Asp Glu Glu Glu Cys Arg Ile Glu Pro Cys Thr Gln

85 90 95

Lys Gly Gln Cys Pro Pro Pro Pro Gly Leu Pro Cys Pro Cys Thr Gly

100 105 110

Val Ser Asp Cys Ser Gly Gly Thr Asp Lys Lys Leu Arg Asn Cys Ser

115 120 125

Arg Leu Ala Cys Leu Ala Gly Glu Leu Arg Cys Thr Leu Ser Asp Asp

130 135 140

Cys Ile Pro Leu Thr Trp Arg Cys Asp Gly His Pro Asp Cys Pro Asp

145 150 155 160

Ser Ser Asp Glu Leu Gly Cys Gly Thr Asn Glu Ile Leu Pro Glu Gly

165 170 175

Asp Ala Thr Thr Met Gly Pro Pro Val Thr Leu Glu Ser Val Thr Ser

180 185 190

Leu Arg Asn Ala Thr Thr Met Gly Pro Pro Val Thr Leu Glu Ser Val

195 200 205

Pro Ser Val Gly Asn Ala Thr Ser Ser Ser Ala Gly Asp Gln Ser Gly

210 215 220

Ser Pro Thr Ala Tyr Gly Val Ile Ala Ala Ala Ala Val Leu Ser Ala

225 230 235 240

Ser Leu Val Thr Ala Thr Leu Leu Leu Leu Ser Trp Leu Arg Ala Gln

245 250 255

Glu Arg Leu Arg Pro Leu Gly Leu Leu Val Ala Met Lys Glu Ser Leu

260 265 270

Leu Leu Ser Glu Gln Lys Thr Ser Leu Pro

275 280

<210> 937

<211> 1127

<212> DNA

<213> Homo sapiens

<400> 937

gcgtgcgcgt gcgcagggat aagagagcgg tctggacagc gcgtggccgg cgccgctgtg 60

gggacagcat gagcggcggt tggatggcgc aggttggagc gtggcgaaca ggggctctgg 120

gcctggcgct gctgctgctg ctcggcctcg gactaggcct ggaggccgcc gcgagcccgc 180

tttccacccc gacctctgcc caggccgcag ggattgagcc atgtacccag aaagggcaat 240

gcccaccgcc ccctggcctc ccctgcccct gcaccggcgt cagtgactgc tctgggggaa 300

ctgacaagaa actgcgcaac tgcagccgcc tggcctgcct agcaggcgag ctccgttgca 360

cgctgagcga tgactgcatt ccactcacgt ggcgctgcga cggccaccca gactgtcccg 420

actccagcga cgagctcggc tgtggaacca atgagatcct cccggaaggg gatgccacaa 480

ccatggggcc ccctgtgacc ctggagagtg tcacctctct caggaatgcc acaaccatgg 540

ggccccctgt gaccctggag agtgtcccct ctgtcgggaa tgccacatcc tcctctgccg 600

gagaccagtc tggaagccca actgcctatg gggttattgc agctgctgcg gtgctcagtg 660

caagcctggt caccgccacc ctcctccttt tgtcctggct ccgagcccag gagcgcctcc 720

gcccactggg gttactggtg gccatgaagg agtccctgct gctgtcagaa cagaagacct 780

cgctgccctg aggacaagca cttgccacca ccgtcactca gccctgggcg tagccggaca 840

ggaggagagc agtgatgcgg atgggtaccc gggcacacca gccctcagag acctgagctc 900

ttctggccac gtggaacctc gaacccgagc tcctgcagaa gtggccctgg agattgaggg 960

tccctggaca ctccctatgg agatccgggg agctaggatg gggaacctgc cacagccaga 1020

actgaggggc tggccccagg cagctcccag ggggtagaac ggccctgtgc ttaagacact 1080

cctgctgccc cgtctgaggg tggcaattaa agttgcttca catcctc 1127

<210> 938

<211> 240

<212> PRT

<213> Homo sapiens

<400> 938

Met Ser Gly Gly Trp Met Ala Gln Val Gly Ala Trp Arg Thr Gly Ala

1 5 10 15

Leu Gly Leu Ala Leu Leu Leu Leu Leu Gly Leu Gly Leu Gly Leu Glu

20 25 30

Ala Ala Ala Ser Pro Leu Ser Thr Pro Thr Ser Ala Gln Ala Ala Gly

35 40 45

Ile Glu Pro Cys Thr Gln Lys Gly Gln Cys Pro Pro Pro Pro Gly Leu

50 55 60

Pro Cys Pro Cys Thr Gly Val Ser Asp Cys Ser Gly Gly Thr Asp Lys

65 70 75 80

Lys Leu Arg Asn Cys Ser Arg Leu Ala Cys Leu Ala Gly Glu Leu Arg

85 90 95

Cys Thr Leu Ser Asp Asp Cys Ile Pro Leu Thr Trp Arg Cys Asp Gly

100 105 110

His Pro Asp Cys Pro Asp Ser Ser Asp Glu Leu Gly Cys Gly Thr Asn

115 120 125

Glu Ile Leu Pro Glu Gly Asp Ala Thr Thr Met Gly Pro Pro Val Thr

130 135 140

Leu Glu Ser Val Thr Ser Leu Arg Asn Ala Thr Thr Met Gly Pro Pro

145 150 155 160

Val Thr Leu Glu Ser Val Pro Ser Val Gly Asn Ala Thr Ser Ser Ser

165 170 175

Ala Gly Asp Gln Ser Gly Ser Pro Thr Ala Tyr Gly Val Ile Ala Ala

180 185 190

Ala Ala Val Leu Ser Ala Ser Leu Val Thr Ala Thr Leu Leu Leu Leu

195 200 205

Ser Trp Leu Arg Ala Gln Glu Arg Leu Arg Pro Leu Gly Leu Leu Val

210 215 220

Ala Met Lys Glu Ser Leu Leu Leu Ser Glu Gln Lys Thr Ser Leu Pro

225 230 235 240

<210> 939

<211> 15735

<212> DNA

<213> Homo sapiens

<400> 939

ggtctaaagg gctttatgca ctgtctggag ggtggggact ggcgcgggta gaaaacggga 60

tgcctcgggc gtgggggcag gcttttggcc actaggagct ggcggaggtg cagacctaaa 120

ggagcgttcg ctagcagagg cgctgccggt gcggtgtgct acgcgcgccc acctcccggg 180

gaaggaacgg cgaggccggg gaccgtcgcg gagatggatc gcgggccggc agcagtggcg 240

tgcacgctgc tcctggctct cgtcgcctgc ctagcgccgg ccagtggcca agaatgtgac 300

agtgcgcatt ttcgctgtgg aagtgggcat tgcatccctg cagactggag gtgtgatggg 360

accaaagact gttcagatga cgcggatgaa attggctgcg ctgttgtgac ctgccagcag 420

ggctatttca agtgccagag tgagggacaa tgcatcccca actcctgggt gtgtgaccaa 480

gatcaagact gtgatgatgg ctcagatgaa cgtcaagatt gctcacaaag tacatgctca 540

agtcatcaga taacatgctc caatggtcag tgtatcccaa gtgaatacag gtgcgaccac 600

gtcagagact gccccgatgg agctgatgag aatgactgcc agtacccaac atgtgagcag 660

cttacttgtg acaatggggc ctgctataac accagtcaga agtgtgattg gaaagttgat 720

tgcagggact cctcagatga aatcaactgc actgagatat gcttgcacaa tgagttttca 780

tgtggcaatg gagagtgtat ccctcgtgct tatgtctgtg accatgacaa tgattgccaa 840

gacggcagtg acgaacatgc ttgcaactat ccgacctgcg gtggttacca gttcacttgc 900

cccagtggcc gatgcattta tcaaaactgg gtttgtgatg gagaagatga ctgtaaagat 960

aatggagatg aagatggatg tgaaagcggt cctcatgatg ttcataaatg ttccccaaga 1020

gaatggtctt gcccagagtc gggacgatgc atctccattt ataaagtttg tgatgggatt 1080

ttagattgcc caggaagaga agatgaaaac aacactagta ccggaaaata ctgtagtatg 1140

actctgtgct ctgccttgaa ctgccagtac cagtgccatg agacgccgta tggaggagcg 1200

tgtttttgtc ccccaggtta tatcatcaac cacaatgaca gccgtacctg tgttgagttt 1260

gatgattgcc agatatgggg aatttgtgac cagaagtgtg aaagccgacc tggccgtcac 1320

ctgtgccact gtgaagaagg gtatatcttg gagcgtggac agtattgcaa agctaatgat 1380

tcctttggcg aggcctccat tatcttctcc aatggtcggg atttgttaat tggtgatatt 1440

catggaagga gcttccggat cctagtggag tctcagaatc gtggagtggc cgtgggtgtg 1500

gctttccact atcacctgca aagagttttt tggacagaca ccgtgcaaaa taaggttttt 1560

tcagttgaca ttaatggttt aaatatccaa gaggttctca atgtttctgt tgaaacccca 1620

gagaacctgg ctgtggactg ggttaataat aaaatctatc tagtggaaac caaggtcaac 1680

cgcatagata tggtaaattt ggatggaagc tatcgggtta cccttataac tgaaaacttg 1740

gggcatccta gaggaattgc cgtggaccca actgttggtt atttattttt ctcagattgg 1800

gagagccttt ctggggaacc taagctggaa agggcattca tggatggcag caaccgtaaa 1860

gacttggtga aaacaaagct gggatggcct gctggggtaa ctctggatat gatatcgaag 1920

cgtgtttact gggttgactc tcggtttgat tacattgaaa ctgtaactta tgatggaatt 1980

caaaggaaga ctgtagttca tggaggctcc ctcattcctc atccctttgg agtaagctta 2040

tttgaaggtc aggtgttctt tacagattgg acaaagatgg ccgtgctgaa ggcaaacaag 2100

ttcacagaga ccaacccaca agtgtactac caggcttccc tgaggcccta tggagtgact 2160

gtttaccatt ccctcagaca gccctatgct accaatccgt gtaaagataa caatgggggc 2220

tgtgagcagg tctgtgtcct cagccacaga acagataatg atggtttggg tttccgttgc 2280

aagtgcacat tcggcttcca actggataca gatgagcgcc actgcattgc tgttcagaat 2340

ttcctcattt tttcatccca agttgctatt cgtgggatcc cgttcacctt gtctacccag 2400

gaagatgtca tggttccagt ttcggggaat ccttctttct ttgtcgggat tgattttgac 2460

gcccaggaca gcactatctt tttttcagat atgtcaaaac acatgatttt taagcaaaag 2520

attgatggca caggaagaga aattctcgca gctaacaggg tggaaaatgt tgaaagtttg 2580

gcttttgatt ggatttcaaa gaatctctat tggacagact ctcattacaa gagtatcagt 2640

gtcatgaggc tagctgataa aacgagacgc acagtagttc agtatttaaa taacccacgg 2700

tcggtggtag ttcatccttt tgccgggtat ctattcttca ctgattggtt ccgtcctgct 2760

aaaattatga gagcatggag tgacggatct cacctcttgc ctgtaataaa cactactctt 2820

ggatggccca atggcttggc catcgattgg gctgcttcac gattgtactg ggtagatgcc 2880

tattttgata aaattgagca cagcaccttt gatggtttag acagaagaag actgggccat 2940

atagagcaga tgacacatcc gtttggactt gccatctttg gagagcattt attttttact 3000

gactggagac tgggtgccat tattcgagtc aggaaagcag atggtggaga aatgacagtt 3060

atccgaagtg gcattgctta catactgcat ttgaaatcgt atgatgtcaa catccagact 3120

ggttctaacg cctgtaatca acccacgcat cctaacggtg actgcagcca cttctgcttc 3180

ccggtgccaa atttccagcg agtgtgtggg tgcccttatg gaatgaggct ggcttccaat 3240

cacttgacat gcgaggggga cccaaccaat gaaccaccca cagagcagtg tggcttattt 3300

tccttcccct gtaaaaatgg cagatgtgtg cccaattact atctctgtga tggagtcgat 3360

gattgtcatg ataacagtga tgagcaacta tgtggcacac ttaataatac ctgttcatct 3420

tcggcgttca cctgtggcca tggggagtgc attcctgcac actggcgctg tgacaaacgc 3480

aacgactgtg tggatggcag tgatgagcac aactgcccca cccacgcacc tgcttcctgc 3540

cttgacaccc aatacacctg tgataatcac cagtgtatct caaagaactg ggtctgtgac 3600

acagacaatg attgtgggga tggatctgat gaaaagaact gcaattcgac agagacatgc 3660

caacctagtc agtttaattg ccccaatcat cgatgtattg acctatcgtt tgtctgtgat 3720

ggtgacaagg attgtgttga tggatctgat gaggttggtt gtgtattaaa ctgtactgct 3780

tctcaattca agtgtgccag tggggataaa tgtattggcg tcacaaatcg ttgtgatggt 3840

gtttttgatt gcagtgacaa ctcggatgaa gcaggctgtc caaccaggcc tcctggtatg 3900

tgccactcag atgaatttca gtgccaagaa gatggtatct gcatcccgaa cttctgggaa 3960

tgtgatgggc atccagactg cctctatgga tctgatgagc acaatgcctg tgtccccaag 4020

acttgccctt catcatattt ccactgtgac aacggaaact gcatccacag ggcatggctc 4080

tgtgatcggg acaatgactg cggggatatg agtgatgaga aggactgccc tactcagccc 4140

tttcgctgtc ctagttggca atggcagtgt cttggccata acatctgtgt gaatctgagt 4200

gtagtgtgtg atggcatctt tgactgcccc aatgggacag atgagtcccc actttgcaat 4260

gggaacagct gctcagattt caatggtggt tgtactcacg agtgtgttca agagcccttt 4320

ggggctaaat gcctatgtcc attgggattc ttacttgcca atgattctaa gacctgtgaa 4380

gacatagatg aatgtgatat tctaggctct tgtagccagc actgttacaa tatgagaggt 4440

tctttccggt gctcgtgtga tacaggctac atgttagaaa gtgatgggag gacttgcaaa 4500

gttacagcat ctgagagtct gctgttactt gtggcaagtc agaacaaaat tattgccgac 4560

agtgtcacct cccaggtcca caatatctat tcattggtcg agaatggttc ttacattgta 4620

gctgttgatt ttgattcaat tagtggtcgt atcttttggt ctgatgcaac tcagggtaaa 4680

acctggagtg cgtttcaaaa tggaacggac agaagagtgg tatttgacag tagcatcatc 4740

ttgactgaaa ctattgcaat agattgggta ggtcgtaatc tttactggac agactatgct 4800

ctggaaacaa ttgaagtctc caaaattgat gggagccaca ggactgtgct gattagtaaa 4860

aacctaacaa atccaagagg actagcatta gatcccagaa tgaatgagca tctactgttc 4920

tggtctgact ggggccacca ccctcgcatc gagcgagcca gcatggacgg cagcatgcgc 4980

actgtcattg tccaggacaa gatcttctgg ccctgcggct taactattga ctaccccaac 5040

agactgctct acttcatgga ctcctatctt gattacatgg acttttgtga ttataatgga 5100

caccatcgga gacaggtgat agccagtgat ttgattatac ggcaccccta tgccctaact 5160

ctctttgaag actctgtgta ctggactgac cgtgctactc gtcgggttat gcgagccaac 5220

aagtggcatg gagggaacca gtcagttgta atgtataata ttcaatggcc ccttgggatt 5280

gttgcggttc atccttcgaa acaaccaaat tccgtgaatc catgtgcctt ttcccgctgc 5340

agccatctct gcctgctttc ctcacagggg cctcattttt actcctgtgt ttgtccttca 5400

ggatggagtc tgtctcctga tctcctgaat tgcttgagag atgatcaacc tttcttaata 5460

actgtaaggc aacatataat ttttggaatc tcccttaatc ctgaggtgaa gagcaatgat 5520

gctatggtcc ccatagcagg gatacagaat ggtttagatg ttgaatttga tgatgctgag 5580

caatacatct attgggttga aaatccaggt gaaattcaca gagtgaagac agatggcacc 5640

aacaggacag tatttgcttc tatatctatg gtggggcctt ctatgaacct ggccttagat 5700

tggatttcaa gaaaccttta ttctaccaat cctagaactc agtcaatcga ggttttgaca 5760

ctccacggag atatcagata cagaaaaaca ttgattgcca atgatgggac agctcttgga 5820

gttggctttc caattggcat aactgttgat cctgctcgtg ggaagctgta ctggtcagac 5880

caaggaactg acagtggggt tcctgccaag atcgccagtg ctaacatgga tggcacatct 5940

gtgaaaactc tctttactgg gaacctcgaa cacctggagt gtgtcactct tgacatcgaa 6000

gagcagaaac tctactgggc agtcactgga agaggagtga ttgaaagagg aaacgtggat 6060

ggaacagatc gaatgatcct ggtacaccag ctttcccacc cctggggaat tgcagtccat 6120

gattctttcc tttattatac tgatgaacag tatgaggtca ttgaaagagt tgataaggcc 6180

actggggcca acaaaatagt cttgagagat aatgttccaa atctgagggg tcttcaagtt 6240

tatcacagac gcaatgccgc cgaatcctca aatggctgta gcaacaacat gaatgcctgt 6300

cagcagattt gcctgcctgt accaggagga ttgttttcct gcgcctgtgc cactggattt 6360

aaactcaatc ctgataatcg gtcctgctct ccatataact ctttcattgt tgtttcaatg 6420

ctgtctgcaa tcagaggctt tagcttggaa ttgtcagatc attcagaaac catggtgccg 6480

gtggcaggcc aaggacgaaa cgcactgcat gtggatgtgg atgtgtcctc tggctttatt 6540

tattggtgtg attttagcag ctcagtggca tctgataatg cgatccgtag aattaaacca 6600

gatggatctt ctctgatgaa cattgtgaca catggaatag gagaaaatgg agtccggggt 6660

attgcagtgg attgggtagc aggaaatctt tatttcacca atgcctttgt ttctgaaaca 6720

ctgatagaag ttctgcggat caatactact taccgccgtg ttcttcttaa agtcacagtg 6780

gacatgccta ggcatattgt tgtagatccc aagaacagat acctcttctg ggctgactat 6840

gggcagagac caaagattga gcgttctttc cttgactgta ccaatcgaac agtgcttgtg 6900

tcagagggca ttgtcacacc acggggcttg gcagtggacc gaagtgatgg ctacgtttat 6960

tgggttgatg attctttaga tataattgca aggattcgta tcaatggaga gaactctgaa 7020

gtgattcgtt atggcagtcg ttacccaact ccttatggca tcactgtttt tgaaaattct 7080

atcatatggg tagataggaa tttgaaaaag atcttccaag ccagcaagga accagagaac 7140

acagagccac ccacagtgat aagagacaat atcaactggc taagagatgt gaccatcttt 7200

gacaagcaag tccagccccg gtcaccagca gaggtcaaca acaacccttg cttggaaaac 7260

aatggtgggt gctctcatct ctgctttgct ctgcctggat tgcacacccc aaaatgtgac 7320

tgtgcctttg ggaccctgca aagtgatggc aagaattgtg ccatttcaac agaaaatttc 7380

ctcatctttg ccttgtctaa ttccttgaga agcttacact tggaccctga aaaccatagc 7440

ccacctttcc aaacaataaa tgtggaaaga actgtcatgt ctctagacta tgacagtgta 7500

agtgatagaa tctacttcac acaaaattta gcctctggag ttggacagat ttcctatgcc 7560

accctgtctt cagggatcca tactccaact gtcattgctt caggtatagg gactgctgat 7620

ggcattgcct ttgactggat tactagaaga atttattaca gtgactacct caaccagatg 7680

attaattcca tggctgaaga tgggtctaac cgcactgtga tagcccgcgt tccaaaacca 7740

agagcaattg tgttagatcc ctgccaaggg tacctgtact gggctgactg ggatacacat 7800

gccaaaatcg agagagccac attgggagga aacttccgcg tacccattgt gaacagcagt 7860

ctggtcatgc ccagtgggct gactctggac tatgaagagg accttctcta ctgggtggat 7920

gctagtctgc agaggattga acgcagcact ctgacgggcg tggatcgtga agtcattgtc 7980

aatgcagccg ttcatgcttt tggcttgact ctctatggcc agtatattta ctggactgac 8040

ttgtacacac aaagaattta ccgagctaac aaatatgacg ggtcaggtca gattgcaatg 8100

accacaaatt tgctctccca gcccagggga atcaacactg ttgtgaagaa ccagaaacaa 8160

cagtgtaaca atccttgtga acagtttaat gggggctgca gccatatctg tgcaccaggt 8220

ccaaatggtg ccgagtgcca gtgtccacat gagggcaact ggtatttggc caacaacagg 8280

aagcactgca ttgtggacaa tggtgaacga tgtggtgcat cttccttcac ctgctccaat 8340

gggcgctgca tctcggaaga gtggaagtgt gataatgaca acgactgtgg ggatggcagt 8400

gatgagatgg aaagtgtctg tgcacttcac acctgctcac cgacagcctt cacctgtgcc 8460

aatgggcgat gtgtccaata ctcttaccgc tgtgattact acaatgactg tggtgatggc 8520

agtgatgagg cagggtgcct gttcagggac tgcaatgcca ccacggagtt tatgtgcaat 8580

aacagaaggt gcatacctcg tgagtttatc tgcaatggtg tagacaactg ccatgataat 8640

aacacttcag atgagaaaaa ttgccctgat cgcacttgcc agtctggata cacaaaatgt 8700

cataattcaa atatttgtat tcctcgcgtt tatttgtgtg acggagacaa tgactgtgga 8760

gataacagtg atgaaaaccc tacttattgc accactcaca cgtgcagcag cagtgagttc 8820

caatgcgcat ctgggcgctg tattcctcaa cattggtatt gtgatcaaga aacagattgt 8880

tttgatgcct ctgatgaacc tgcctcttgt ggtcactctg agcgaacatg cctagctgat 8940

gagttcaagt gtgatggtgg gaggtgcatc ccaagcgaat ggatctgtga cggtgataat 9000

gactgtgggg atatgagtga cgaggataaa aggcaccagt gtcagaatca aaactgctcg 9060

gattccgagt ttctctgtgt aaatgacaga cctccggaca ggaggtgcat tccccagtct 9120

tgggtctgtg atggcgatgt ggattgtact gacggctacg atgagaatca gaattgcacc 9180

aggagaactt gctctgaaaa tgaattcacc tgtggttacg gactgtgtat cccaaagata 9240

ttcaggtgtg accggcacaa tgactgtggt gactatagcg acgagagggg ctgcttatac 9300

cagacttgcc aacagaatca gtttacctgt cagaacgggc gctgcattag taaaaccttc 9360

gtctgtgatg aggataatga ctgtggagac ggatctgatg agctgatgca cctgtgccac 9420

accccagaac ccacgtgtcc acctcacgag ttcaagtgtg acaatgggcg ctgcatcgag 9480

atgatgaaac tctgcaacca cctagatgac tgtttggaca acagcgatga gaaaggctgt 9540

ggcattaatg aatgccatga cccttcaatc agtggctgcg atcacaactg cacagacacc 9600

ttaaccagtt tctattgttc ctgtcgtcct ggttacaagc tcatgtctga caagcggact 9660

tgtgttgata ttgatgaatg cacagagatg ccttttgtct gtagccagaa gtgtgagaat 9720

gtaataggct cctacatctg taagtgtgcc ccaggctacc tccgagaacc agatggaaag 9780

acctgccggc aaaacagtaa catcgaaccc tatctcattt ttagcaaccg ttactatttg 9840

agaaatttaa ctatagatgg ctatttttac tccctcatct tggaaggact ggacaatgtt 9900

gtggcattag attttgaccg agtagagaag agattgtatt ggattgatac acagaggcaa 9960

gtcattgaga gaatgtttct gaataagaca aacaaggaga caatcataaa ccacagacta 10020

ccagctgcag aaagtctggc tgtagactgg gtttccagaa agctctactg gttggatgcc 10080

cgcctggatg gcctctttgt ctctgacctc aatggtggac accgccgcat gctggcccag 10140

cactgtgtgg atgccaacaa caccttctgc tttgataatc ccagaggact tgcccttcac 10200

cctcaatatg ggtacctcta ctgggcagac tggggtcacc gcgcatacat tgggagagta 10260

ggcatggatg gaaccaacaa gtctgtgata atctccacca agttagagtg gcctaatggc 10320

atcaccattg attacaccaa tgatctactc tactgggcag atgcccacct gggttacata 10380

gagtactctg atttggaggg ccaccatcga cacacggtgt atgatggggc actgcctcac 10440

cctttcgcta ttaccatttt tgaagacact atttattgga cagattggaa tacaaggaca 10500

gtggaaaagg gaaacaaata tgatggatca aatagacaga cactggtgaa cacaacacac 10560

agaccatttg acatccatgt gtaccatcca tataggcagc ccattgtgag caatccctgt 10620

ggtaccaaca atggtggctg ttctcatctc tgcctcatca agccaggagg aaaagggttc 10680

acttgcgagt gtccagatga cttccgcacc cttcagctga gtggcagcac ctactgcatg 10740

cccatgtgct ccagcaccca gttcctgtgc gctaacaatg aaaagtgcat tcctatctgg 10800

tggaaatgtg atggacagaa agactgctca gatggctctg atgaactggc cctttgcccg 10860

cagcgcttct gccgactggg acagttccag tgcagtgacg gcaactgcac cagcccgcag 10920

actttatgca atgctcacca aaattgccct gatgggtctg atgaagaccg tcttctttgt 10980

gagaatcacc actgtgactc caatgaatgg cagtgcgcca acaaacgttg catcccagaa 11040

tcctggcagt gtgacacatt taacgactgt gaggataact cagatgaaga cagttcccac 11100

tgtgccagca ggacctgccg gccgggccag tttcggtgtg ctaatggccg ctgcatcccg 11160

caggcctgga agtgtgatgt ggataatgat tgtggagacc actcggatga gcccattgaa 11220

gaatgcatga gctctgccca tctctgtgac aacttcacag aattcagctg caaaacaaat 11280

taccgctgca tcccaaagtg ggccgtgtgc aatggtgtag atgactgcag ggacaacagt 11340

gatgagcaag gctgtgagga gaggacatgc catcctgtgg gggatttccg ctgtaaaaat 11400

caccactgca tccctcttcg ttggcagtgt gatgggcaaa atgactgtgg agataactca 11460

gatgaggaaa actgtgctcc ccgggagtgc acagagagcg agtttcgatg tgtcaatcag 11520

cagtgcattc cctcgcgatg gatctgtgac cattacaacg actgtgggga caactcagat 11580

gaacgggact gtgagatgag gacctgccat cctgaatatt ttcagtgtac aagtggacat 11640

tgtgtacaca gtgaactgaa atgcgatgga tccgctgact gtttggatgc gtctgatgaa 11700

gctgattgtc ccacacgctt tcctgatggt gcatactgcc aggctactat gttcgaatgc 11760

aaaaaccatg tttgtatccc gccatattgg aaatgtgatg gcgatgatga ctgtggcgat 11820

ggttcagatg aagaacttca cctgtgcttg gatgttccct gtaattcacc aaaccgtttc 11880

cggtgtgaca acaatcgctg catttatagt catgaggtgt gcaatggtgt ggatgactgt 11940

ggagatggaa ctgatgagac agaggagcac tgtagaaaac cgacccctaa accttgtaca 12000

gaatatgaat ataagtgtgg caatgggcat tgcattccac atgacaatgt gtgtgatgat 12060

gccgatgact gtggtgactg gtccgatgaa ctgggttgca ataaaggaaa agaaagaaca 12120

tgtgctgaaa atatatgcga gcaaaattgt acccaattaa atgaaggagg atttatctgc 12180

tcctgtacag ctgggttcga aaccaatgtt tttgacagaa cctcctgtct agatatcaat 12240

gaatgtgaac aatttgggac ttgtccccag cactgcagaa ataccaaagg aagttatgag 12300

tgtgtctgtg ctgatggctt cacgtctatg agtgaccgcc ctggaaaacg atgtgcagct 12360

gagggtagct ctcctttgtt gctactgcct gacaatgtcc gaattcgaaa atataatctc 12420

tcatctgaga ggttctcaga gtatcttcaa gatgaggaat atatccaagc tgttgattat 12480

gattgggatc ccaaggacat aggcctcagt gttgtgtatt acactgtgcg aggggagggc 12540

tctaggtttg gtgctatcaa acgtgcctac atccccaact ttgaatccgg ccgcaataat 12600

cttgtgcagg aagttgacct gaaactgaaa tacgtaatgc agccagatgg aatagcagtg 12660

gactgggttg gaaggcatat ttactggtca gatgtcaaga ataaacgcat tgaggtggct 12720

aaacttgatg gaaggtacag aaagtggctg atttccactg acctggacca accagctgct 12780

attgctgtga atcccaaact agggcttatg ttctggactg actggggaaa ggaacctaaa 12840

atcgagtctg cctggatgaa tggagaggac cgcaacatcc tggttttcga ggaccttggt 12900

tggccaactg gcctttctat cgattatttg aacaatgacc gaatctactg gagtgacttc 12960

aaggaggacg ttattgaaac cataaaatat gatgggactg ataggagagt cattgcaaag 13020

gaagcaatga acccttacag cctggacatc tttgaagacc agttatactg gatatctaag 13080

gaaaagggag aagtatggaa acaaaataaa tttgggcaag gaaagaaaga gaaaacgctg 13140

gtagtgaacc cttggctcac tcaagttcga atctttcatc aactcagata caataagtca 13200

gtgcccaacc tttgcaaaca gatctgcagc cacctctgcc ttctgagacc tggaggatac 13260

agctgtgcct gtccccaagg ctccagcttt atagagggga gcaccactga gtgtgatgca 13320

gccatcgaac tgcctatcaa cctgcccccc ccatgcaggt gcatgcacgg aggaaattgc 13380

tattttgatg agactgacct ccccaaatgc aagtgtccta gcggctacac cggaaaatat 13440

tgtgaaatgg cgttttcaaa aggcatctct ccaggaacaa ccgcagtagc tgtgctgttg 13500

acaatcctct tgatcgtcgt aattggagct ctggcaattg caggattctt ccactataga 13560

aggaccggct cccttttgcc tgctctgccc aagctgccaa gcttaagcag tctcgtcaag 13620

ccctctgaaa atgggaatgg ggtgaccttc agatcagggg cagatcttaa catggatatt 13680

ggagtgtctg gttttggacc tgagactgct attgacaggt caatggcaat gagtgaagac 13740

tttgtcatgg aaatggggaa gcagcccata atatttgaaa acccaatgta ctcagccaga 13800

gacagtgctg tcaaagtggt tcagccaatc caggtgactg tatctgaaaa tgtggataat 13860

aagaattatg gaagtcccat aaacccttct gagatagttc cagagacaaa cccaacttca 13920

ccagctgctg atggaactca ggtgacaaaa tggaatctct tcaaacgaaa atctaaacaa 13980

actaccaact ttgaaaatcc aatctatgca cagatggaga acgagcaaaa ggaaagtgtt 14040

gctgcgacac cacctccatc accttcgctc cctgctaagc ctaagcctcc ttcgagaaga 14100

gacccaactc caacctattc tgcaacagaa gacactttta aagacaccgc aaatcttgtt 14160

aaagaagact ctgaagtata gctataccag ctatttaggg aataattaga aacacacttt 14220

tgcacatata ttttttacaa acagatgaaa aaagttaaca ttcagtactt tatgaaaaaa 14280

atatattttt ccctgtttgc ctatagttgg aggtatcctg tgtgtctttt tttacttatg 14340

ccgtctcata tttttacaaa taattatcac aatgtactat atgtatatct ttgcactgaa 14400

gttgtctgaa ggtaatacta taaatatatt gtatatttgt aaattttgga aagattatcc 14460

tgttactgaa tttgctaata aagatgtctg ctgatttggt tggtgatcat tatagtaaat 14520

gatccaacaa gaaaaggaat tgactgggga cctttagccg tgtctaaaga agaggcacca 14580

ctcatatttc ctataaaatt atctaggaaa ggaatccagg ccccgctctt gggtccattt 14640

ttacacatta gcacttaatt aatgttcaat attacatgtc aatttgatta atggctatgt 14700

tgataggggc cactatgtgt tgtatagaca tctggacttg actgtagact cctcagataa 14760

tacagaaggt aggaaaagca attcagtttg gcccttctgt gtgttggcat tgtctaacca 14820

gaactctctg tttcatgtgt gttctctcac tagctgccaa gacaacattt ttatttgtga 14880

tgtctatgag gaaatcccat atcattaagt gccagtgtcc tgcattgagt ttgtggttaa 14940

ttaaatgagc tcttctgctg atggaccctg gagcaatttc tcccctcacc tgacattcaa 15000

ggtggtcacc tgccctagta gttggagctc agtagctgaa tttctgaaac caaatctgtg 15060

tcttcataaa ataaggtgca aaaaaaaaaa ataccagtta agtaaagcct caactgggtt 15120

tttgtttcta tgaaaatatc attataatca ctatttattt cctaagttga acctgaatag 15180

aaagggaaac cattcttatt aagcttttta ttaggccctg tggctaaatg tgtacattta 15240

tattagaatg tactgtacag tccagatctt ttctttaatt cttattggtt tttttttttt 15300

tttttttttt agagatggag tcttgctata ttgccaaggc tgatcttgaa gtcctgggct 15360

caagtgatcc tcccacctca gcctcctgag tggttggggt tacgggcgtg agccactgtg 15420

cctggcttcc agctctcctc ttaaatagtg ggtatagtct gcacaacagg aaccatggca 15480

ggaatataca ctttcccata gcaaatagca tacctgactc tctgtgctaa tattgcacat 15540

ttgttaaaca atgaatgaat ggatggatgg atggatggat gaatgaatga aacatatact 15600

actgattatt ttattccaga gttctcaaaa tatttgttgc tgatattttg agtgctgact 15660

gtaattactt tgattagata aacaactgga aataatgctg ctgaaaaagt tctaataaat 15720

gtgtatttta tcaga 15735

<210> 940

<211> 4655

<212> PRT

<213> Homo sapiens

<400> 940

Met Asp Arg Gly Pro Ala Ala Val Ala Cys Thr Leu Leu Leu Ala Leu

1 5 10 15

Val Ala Cys Leu Ala Pro Ala Ser Gly Gln Glu Cys Asp Ser Ala His

20 25 30

Phe Arg Cys Gly Ser Gly His Cys Ile Pro Ala Asp Trp Arg Cys Asp

35 40 45

Gly Thr Lys Asp Cys Ser Asp Asp Ala Asp Glu Ile Gly Cys Ala Val

50 55 60

Val Thr Cys Gln Gln Gly Tyr Phe Lys Cys Gln Ser Glu Gly Gln Cys

65 70 75 80

Ile Pro Asn Ser Trp Val Cys Asp Gln Asp Gln Asp Cys Asp Asp Gly

85 90 95

Ser Asp Glu Arg Gln Asp Cys Ser Gln Ser Thr Cys Ser Ser His Gln

100 105 110

Ile Thr Cys Ser Asn Gly Gln Cys Ile Pro Ser Glu Tyr Arg Cys Asp

115 120 125

His Val Arg Asp Cys Pro Asp Gly Ala Asp Glu Asn Asp Cys Gln Tyr

130 135 140

Pro Thr Cys Glu Gln Leu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr

145 150 155 160

Ser Gln Lys Cys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu

165 170 175

Ile Asn Cys Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn

180 185 190

Gly Glu Cys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys

195 200 205

Gln Asp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly

210 215 220

Tyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val

225 230 235 240

Cys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp Gly Cys

245 250 255

Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu Trp Ser

260 265 270

Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val Cys Asp Gly

275 280 285

Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn Thr Ser Thr Gly

290 295 300

Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu Asn Cys Gln Tyr Gln

305 310 315 320

Cys His Glu Thr Pro Tyr Gly Gly Ala Cys Phe Cys Pro Pro Gly Tyr

325 330 335

Ile Ile Asn His Asn Asp Ser Arg Thr Cys Val Glu Phe Asp Asp Cys

340 345 350

Gln Ile Trp Gly Ile Cys Asp Gln Lys Cys Glu Ser Arg Pro Gly Arg

355 360 365

His Leu Cys His Cys Glu Glu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr

370 375 380

Cys Lys Ala Asn Asp Ser Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn

385 390 395 400

Gly Arg Asp Leu Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile

405 410 415

Leu Val Glu Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His

420 425 430

Tyr His Leu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys Val

435 440 445

Phe Ser Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn Val

450 455 460

Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys

465 470 475 480

Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val Asn Leu

485 490 495

Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu Gly His Pro

500 505 510

Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu Phe Phe Ser Asp

515 520 525

Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu Arg Ala Phe Met Asp

530 535 540

Gly Ser Asn Arg Lys Asp Leu Val Lys Thr Lys Leu Gly Trp Pro Ala

545 550 555 560

Gly Val Thr Leu Asp Met Ile Ser Lys Arg Val Tyr Trp Val Asp Ser

565 570 575

Arg Phe Asp Tyr Ile Glu Thr Val Thr Tyr Asp Gly Ile Gln Arg Lys

580 585 590

Thr Val Val His Gly Gly Ser Leu Ile Pro His Pro Phe Gly Val Ser

595 600 605

Leu Phe Glu Gly Gln Val Phe Phe Thr Asp Trp Thr Lys Met Ala Val

610 615 620

Leu Lys Ala Asn Lys Phe Thr Glu Thr Asn Pro Gln Val Tyr Tyr Gln

625 630 635 640

Ala Ser Leu Arg Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg Gln

645 650 655

Pro Tyr Ala Thr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu Gln

660 665 670

Val Cys Val Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe Arg

675 680 685

Cys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His Cys

690 695 700

Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg

705 710 715 720

Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val Met Val Pro Val

725 730 735

Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe Asp Ala Gln Asp

740 745 750

Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His Met Ile Phe Lys Gln

755 760 765

Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu Ala Ala Asn Arg Val Glu

770 775 780

Asn Val Glu Ser Leu Ala Phe Asp Trp Ile Ser Lys Asn Leu Tyr Trp

785 790 795 800

Thr Asp Ser His Tyr Lys Ser Ile Ser Val Met Arg Leu Ala Asp Lys

805 810 815

Thr Arg Arg Thr Val Val Gln Tyr Leu Asn Asn Pro Arg Ser Val Val

820 825 830

Val His Pro Phe Ala Gly Tyr Leu Phe Phe Thr Asp Trp Phe Arg Pro

835 840 845

Ala Lys Ile Met Arg Ala Trp Ser Asp Gly Ser His Leu Leu Pro Val

850 855 860

Ile Asn Thr Thr Leu Gly Trp Pro Asn Gly Leu Ala Ile Asp Trp Ala

865 870 875 880

Ala Ser Arg Leu Tyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu His

885 890 895

Ser Thr Phe Asp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu Gln

900 905 910

Met Thr His Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe Phe

915 920 925

Thr Asp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly

930 935 940

Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu

945 950 955 960

Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala Cys Asn Gln

965 970 975

Pro Thr His Pro Asn Gly Asp Cys Ser His Phe Cys Phe Pro Val Pro

980 985 990

Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly Met Arg Leu Ala Ser

995 1000 1005

Asn His Leu Thr Cys Glu Gly Asp Pro Thr Asn Glu Pro Pro Thr

1010 1015 1020

Glu Gln Cys Gly Leu Phe Ser Phe Pro Cys Lys Asn Gly Arg Cys

1025 1030 1035

Val Pro Asn Tyr Tyr Leu Cys Asp Gly Val Asp Asp Cys His Asp

1040 1045 1050

Asn Ser Asp Glu Gln Leu Cys Gly Thr Leu Asn Asn Thr Cys Ser

1055 1060 1065

Ser Ser Ala Phe Thr Cys Gly His Gly Glu Cys Ile Pro Ala His

1070 1075 1080

Trp Arg Cys Asp Lys Arg Asn Asp Cys Val Asp Gly Ser Asp Glu

1085 1090 1095

His Asn Cys Pro Thr His Ala Pro Ala Ser Cys Leu Asp Thr Gln

1100 1105 1110

Tyr Thr Cys Asp Asn His Gln Cys Ile Ser Lys Asn Trp Val Cys

1115 1120 1125

Asp Thr Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Lys Asn Cys

1130 1135 1140

Asn Ser Thr Glu Thr Cys Gln Pro Ser Gln Phe Asn Cys Pro Asn

1145 1150 1155

His Arg Cys Ile Asp Leu Ser Phe Val Cys Asp Gly Asp Lys Asp

1160 1165 1170

Cys Val Asp Gly Ser Asp Glu Val Gly Cys Val Leu Asn Cys Thr

1175 1180 1185

Ala Ser Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys Ile Gly Val

1190 1195 1200

Thr Asn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn Ser Asp

1205 1210 1215

Glu Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser Asp

1220 1225 1230

Glu Phe Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn Phe Trp

1235 1240 1245

Glu Cys Asp Gly His Pro Asp Cys Leu Tyr Gly Ser Asp Glu His

1250 1255 1260

Asn Ala Cys Val Pro Lys Thr Cys Pro Ser Ser Tyr Phe His Cys

1265 1270 1275

Asp Asn Gly Asn Cys Ile His Arg Ala Trp Leu Cys Asp Arg Asp

1280 1285 1290

Asn Asp Cys Gly Asp Met Ser Asp Glu Lys Asp Cys Pro Thr Gln

1295 1300 1305

Pro Phe Arg Cys Pro Ser Trp Gln Trp Gln Cys Leu Gly His Asn

1310 1315 1320

Ile Cys Val Asn Leu Ser Val Val Cys Asp Gly Ile Phe Asp Cys

1325 1330 1335

Pro Asn Gly Thr Asp Glu Ser Pro Leu Cys Asn Gly Asn Ser Cys

1340 1345 1350

Ser Asp Phe Asn Gly Gly Cys Thr His Glu Cys Val Gln Glu Pro

1355 1360 1365

Phe Gly Ala Lys Cys Leu Cys Pro Leu Gly Phe Leu Leu Ala Asn

1370 1375 1380

Asp Ser Lys Thr Cys Glu Asp Ile Asp Glu Cys Asp Ile Leu Gly

1385 1390 1395

Ser Cys Ser Gln His Cys Tyr Asn Met Arg Gly Ser Phe Arg Cys

1400 1405 1410

Ser Cys Asp Thr Gly Tyr Met Leu Glu Ser Asp Gly Arg Thr Cys

1415 1420 1425

Lys Val Thr Ala Ser Glu Ser Leu Leu Leu Leu Val Ala Ser Gln

1430 1435 1440

Asn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His Asn Ile

1445 1450 1455

Tyr Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp Phe

1460 1465 1470

Asp Ser Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr Gln Gly

1475 1480 1485

Lys Thr Trp Ser Ala Phe Gln Asn Gly Thr Asp Arg Arg Val Val

1490 1495 1500

Phe Asp Ser Ser Ile Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp

1505 1510 1515

Val Gly Arg Asn Leu Tyr Trp Thr Asp Tyr Ala Leu Glu Thr Ile

1520 1525 1530

Glu Val Ser Lys Ile Asp Gly Ser His Arg Thr Val Leu Ile Ser

1535 1540 1545

Lys Asn Leu Thr Asn Pro Arg Gly Leu Ala Leu Asp Pro Arg Met

1550 1555 1560

Asn Glu His Leu Leu Phe Trp Ser Asp Trp Gly His His Pro Arg

1565 1570 1575

Ile Glu Arg Ala Ser Met Asp Gly Ser Met Arg Thr Val Ile Val

1580 1585 1590

Gln Asp Lys Ile Phe Trp Pro Cys Gly Leu Thr Ile Asp Tyr Pro

1595 1600 1605

Asn Arg Leu Leu Tyr Phe Met Asp Ser Tyr Leu Asp Tyr Met Asp

1610 1615 1620

Phe Cys Asp Tyr Asn Gly His His Arg Arg Gln Val Ile Ala Ser

1625 1630 1635

Asp Leu Ile Ile Arg His Pro Tyr Ala Leu Thr Leu Phe Glu Asp

1640 1645 1650

Ser Val Tyr Trp Thr Asp Arg Ala Thr Arg Arg Val Met Arg Ala

1655 1660 1665

Asn Lys Trp His Gly Gly Asn Gln Ser Val Val Met Tyr Asn Ile

1670 1675 1680

Gln Trp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys Gln Pro

1685 1690 1695

Asn Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu Cys

1700 1705 1710

Leu Leu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys Pro

1715 1720 1725

Ser Gly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg Asp

1730 1735 1740

Asp Gln Pro Phe Leu Ile Thr Val Arg Gln His Ile Ile Phe Gly

1745 1750 1755

Ile Ser Leu Asn Pro Glu Val Lys Ser Asn Asp Ala Met Val Pro

1760 1765 1770

Ile Ala Gly Ile Gln Asn Gly Leu Asp Val Glu Phe Asp Asp Ala

1775 1780 1785

Glu Gln Tyr Ile Tyr Trp Val Glu Asn Pro Gly Glu Ile His Arg

1790 1795 1800

Val Lys Thr Asp Gly Thr Asn Arg Thr Val Phe Ala Ser Ile Ser

1805 1810 1815

Met Val Gly Pro Ser Met Asn Leu Ala Leu Asp Trp Ile Ser Arg

1820 1825 1830

Asn Leu Tyr Ser Thr Asn Pro Arg Thr Gln Ser Ile Glu Val Leu

1835 1840 1845

Thr Leu His Gly Asp Ile Arg Tyr Arg Lys Thr Leu Ile Ala Asn

1850 1855 1860

Asp Gly Thr Ala Leu Gly Val Gly Phe Pro Ile Gly Ile Thr Val

1865 1870 1875

Asp Pro Ala Arg Gly Lys Leu Tyr Trp Ser Asp Gln Gly Thr Asp

1880 1885 1890

Ser Gly Val Pro Ala Lys Ile Ala Ser Ala Asn Met Asp Gly Thr

1895 1900 1905

Ser Val Lys Thr Leu Phe Thr Gly Asn Leu Glu His Leu Glu Cys

1910 1915 1920

Val Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp Ala Val Thr

1925 1930 1935

Gly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr Asp Arg

1940 1945 1950

Met Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala Val

1955 1960 1965

His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val Ile

1970 1975 1980

Glu Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu Arg

1985 1990 1995

Asp Asn Val Pro Asn Leu Arg Gly Leu Gln Val Tyr His Arg Arg

2000 2005 2010

Asn Ala Ala Glu Ser Ser Asn Gly Cys Ser Asn Asn Met Asn Ala

2015 2020 2025

Cys Gln Gln Ile Cys Leu Pro Val Pro Gly Gly Leu Phe Ser Cys

2030 2035 2040

Ala Cys Ala Thr Gly Phe Lys Leu Asn Pro Asp Asn Arg Ser Cys

2045 2050 2055

Ser Pro Tyr Asn Ser Phe Ile Val Val Ser Met Leu Ser Ala Ile

2060 2065 2070

Arg Gly Phe Ser Leu Glu Leu Ser Asp His Ser Glu Thr Met Val

2075 2080 2085

Pro Val Ala Gly Gln Gly Arg Asn Ala Leu His Val Asp Val Asp

2090 2095 2100

Val Ser Ser Gly Phe Ile Tyr Trp Cys Asp Phe Ser Ser Ser Val

2105 2110 2115

Ala Ser Asp Asn Ala Ile Arg Arg Ile Lys Pro Asp Gly Ser Ser

2120 2125 2130

Leu Met Asn Ile Val Thr His Gly Ile Gly Glu Asn Gly Val Arg

2135 2140 2145

Gly Ile Ala Val Asp Trp Val Ala Gly Asn Leu Tyr Phe Thr Asn

2150 2155 2160

Ala Phe Val Ser Glu Thr Leu Ile Glu Val Leu Arg Ile Asn Thr

2165 2170 2175

Thr Tyr Arg Arg Val Leu Leu Lys Val Thr Val Asp Met Pro Arg

2180 2185 2190

His Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala Asp

2195 2200 2205

Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp Cys Thr

2210 2215 2220

Asn Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro Arg Gly

2225 2230 2235

Leu Ala Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp Val Asp Asp

2240 2245 2250

Ser Leu Asp Ile Ile Ala Arg Ile Arg Ile Asn Gly Glu Asn Ser

2255 2260 2265

Glu Val Ile Arg Tyr Gly Ser Arg Tyr Pro Thr Pro Tyr Gly Ile

2270 2275 2280

Thr Val Phe Glu Asn Ser Ile Ile Trp Val Asp Arg Asn Leu Lys

2285 2290 2295

Lys Ile Phe Gln Ala Ser Lys Glu Pro Glu Asn Thr Glu Pro Pro

2300 2305 2310

Thr Val Ile Arg Asp Asn Ile Asn Trp Leu Arg Asp Val Thr Ile

2315 2320 2325

Phe Asp Lys Gln Val Gln Pro Arg Ser Pro Ala Glu Val Asn Asn

2330 2335 2340

Asn Pro Cys Leu Glu Asn Asn Gly Gly Cys Ser His Leu Cys Phe

2345 2350 2355

Ala Leu Pro Gly Leu His Thr Pro Lys Cys Asp Cys Ala Phe Gly

2360 2365 2370

Thr Leu Gln Ser Asp Gly Lys Asn Cys Ala Ile Ser Thr Glu Asn

2375 2380 2385

Phe Leu Ile Phe Ala Leu Ser Asn Ser Leu Arg Ser Leu His Leu

2390 2395 2400

Asp Pro Glu Asn His Ser Pro Pro Phe Gln Thr Ile Asn Val Glu

2405 2410 2415

Arg Thr Val Met Ser Leu Asp Tyr Asp Ser Val Ser Asp Arg Ile

2420 2425 2430

Tyr Phe Thr Gln Asn Leu Ala Ser Gly Val Gly Gln Ile Ser Tyr

2435 2440 2445

Ala Thr Leu Ser Ser Gly Ile His Thr Pro Thr Val Ile Ala Ser

2450 2455 2460

Gly Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp Trp Ile Thr Arg

2465 2470 2475

Arg Ile Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile Asn Ser Met

2480 2485 2490

Ala Glu Asp Gly Ser Asn Arg Thr Val Ile Ala Arg Val Pro Lys

2495 2500 2505

Pro Arg Ala Ile Val Leu Asp Pro Cys Gln Gly Tyr Leu Tyr Trp

2510 2515 2520

Ala Asp Trp Asp Thr His Ala Lys Ile Glu Arg Ala Thr Leu Gly

2525 2530 2535

Gly Asn Phe Arg Val Pro Ile Val Asn Ser Ser Leu Val Met Pro

2540 2545 2550

Ser Gly Leu Thr Leu Asp Tyr Glu Glu Asp Leu Leu Tyr Trp Val

2555 2560 2565

Asp Ala Ser Leu Gln Arg Ile Glu Arg Ser Thr Leu Thr Gly Val

2570 2575 2580

Asp Arg Glu Val Ile Val Asn Ala Ala Val His Ala Phe Gly Leu

2585 2590 2595

Thr Leu Tyr Gly Gln Tyr Ile Tyr Trp Thr Asp Leu Tyr Thr Gln

2600 2605 2610

Arg Ile Tyr Arg Ala Asn Lys Tyr Asp Gly Ser Gly Gln Ile Ala

2615 2620 2625

Met Thr Thr Asn Leu Leu Ser Gln Pro Arg Gly Ile Asn Thr Val

2630 2635 2640

Val Lys Asn Gln Lys Gln Gln Cys Asn Asn Pro Cys Glu Gln Phe

2645 2650 2655

Asn Gly Gly Cys Ser His Ile Cys Ala Pro Gly Pro Asn Gly Ala

2660 2665 2670

Glu Cys Gln Cys Pro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn

2675 2680 2685

Arg Lys His Cys Ile Val Asp Asn Gly Glu Arg Cys Gly Ala Ser

2690 2695 2700

Ser Phe Thr Cys Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys

2705 2710 2715

Cys Asp Asn Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Met Glu

2720 2725 2730

Ser Val Cys Ala Leu His Thr Cys Ser Pro Thr Ala Phe Thr Cys

2735 2740 2745

Ala Asn Gly Arg Cys Val Gln Tyr Ser Tyr Arg Cys Asp Tyr Tyr

2750 2755 2760

Asn Asp Cys Gly Asp Gly Ser Asp Glu Ala Gly Cys Leu Phe Arg

2765 2770 2775

Asp Cys Asn Ala Thr Thr Glu Phe Met Cys Asn Asn Arg Arg Cys

2780 2785 2790

Ile Pro Arg Glu Phe Ile Cys Asn Gly Val Asp Asn Cys His Asp

2795 2800 2805

Asn Asn Thr Ser Asp Glu Lys Asn Cys Pro Asp Arg Thr Cys Gln

2810 2815 2820

Ser Gly Tyr Thr Lys Cys His Asn Ser Asn Ile Cys Ile Pro Arg

2825 2830 2835

Val Tyr Leu Cys Asp Gly Asp Asn Asp Cys Gly Asp Asn Ser Asp

2840 2845 2850

Glu Asn Pro Thr Tyr Cys Thr Thr His Thr Cys Ser Ser Ser Glu

2855 2860 2865

Phe Gln Cys Ala Ser Gly Arg Cys Ile Pro Gln His Trp Tyr Cys

2870 2875 2880

Asp Gln Glu Thr Asp Cys Phe Asp Ala Ser Asp Glu Pro Ala Ser

2885 2890 2895

Cys Gly His Ser Glu Arg Thr Cys Leu Ala Asp Glu Phe Lys Cys

2900 2905 2910

Asp Gly Gly Arg Cys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp

2915 2920 2925

Asn Asp Cys Gly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys

2930 2935 2940

Gln Asn Gln Asn Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp

2945 2950 2955

Arg Pro Pro Asp Arg Arg Cys Ile Pro Gln Ser Trp Val Cys Asp

2960 2965 2970

Gly Asp Val Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln Asn Cys

2975 2980 2985

Thr Arg Arg Thr Cys Ser Glu Asn Glu Phe Thr Cys Gly Tyr Gly

2990 2995 3000

Leu Cys Ile Pro Lys Ile Phe Arg Cys Asp Arg His Asn Asp Cys

3005 3010 3015

Gly Asp Tyr Ser Asp Glu Arg Gly Cys Leu Tyr Gln Thr Cys Gln

3020 3025 3030

Gln Asn Gln Phe Thr Cys Gln Asn Gly Arg Cys Ile Ser Lys Thr

3035 3040 3045

Phe Val Cys Asp Glu Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu

3050 3055 3060

Leu Met His Leu Cys His Thr Pro Glu Pro Thr Cys Pro Pro His

3065 3070 3075

Glu Phe Lys Cys Asp Asn Gly Arg Cys Ile Glu Met Met Lys Leu

3080 3085 3090

Cys Asn His Leu Asp Asp Cys Leu Asp Asn Ser Asp Glu Lys Gly

3095 3100 3105

Cys Gly Ile Asn Glu Cys His Asp Pro Ser Ile Ser Gly Cys Asp

3110 3115 3120

His Asn Cys Thr Asp Thr Leu Thr Ser Phe Tyr Cys Ser Cys Arg

3125 3130 3135

Pro Gly Tyr Lys Leu Met Ser Asp Lys Arg Thr Cys Val Asp Ile

3140 3145 3150

Asp Glu Cys Thr Glu Met Pro Phe Val Cys Ser Gln Lys Cys Glu

3155 3160 3165

Asn Val Ile Gly Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu

3170 3175 3180

Arg Glu Pro Asp Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu

3185 3190 3195

Pro Tyr Leu Ile Phe Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr

3200 3205 3210

Ile Asp Gly Tyr Phe Tyr Ser Leu Ile Leu Glu Gly Leu Asp Asn

3215 3220 3225

Val Val Ala Leu Asp Phe Asp Arg Val Glu Lys Arg Leu Tyr Trp

3230 3235 3240

Ile Asp Thr Gln Arg Gln Val Ile Glu Arg Met Phe Leu Asn Lys

3245 3250 3255

Thr Asn Lys Glu Thr Ile Ile Asn His Arg Leu Pro Ala Ala Glu

3260 3265 3270

Ser Leu Ala Val Asp Trp Val Ser Arg Lys Leu Tyr Trp Leu Asp

3275 3280 3285

Ala Arg Leu Asp Gly Leu Phe Val Ser Asp Leu Asn Gly Gly His

3290 3295 3300

Arg Arg Met Leu Ala Gln His Cys Val Asp Ala Asn Asn Thr Phe

3305 3310 3315

Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu His Pro Gln Tyr Gly

3320 3325 3330

Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala Tyr Ile Gly Arg

3335 3340 3345

Val Gly Met Asp Gly Thr Asn Lys Ser Val Ile Ile Ser Thr Lys

3350 3355 3360

Leu Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr Thr Asn Asp Leu

3365 3370 3375

Leu Tyr Trp Ala Asp Ala His Leu Gly Tyr Ile Glu Tyr Ser Asp

3380 3385 3390

Leu Glu Gly His His Arg His Thr Val Tyr Asp Gly Ala Leu Pro

3395 3400 3405

His Pro Phe Ala Ile Thr Ile Phe Glu Asp Thr Ile Tyr Trp Thr

3410 3415 3420

Asp Trp Asn Thr Arg Thr Val Glu Lys Gly Asn Lys Tyr Asp Gly

3425 3430 3435

Ser Asn Arg Gln Thr Leu Val Asn Thr Thr His Arg Pro Phe Asp

3440 3445 3450

Ile His Val Tyr His Pro Tyr Arg Gln Pro Ile Val Ser Asn Pro

3455 3460 3465

Cys Gly Thr Asn Asn Gly Gly Cys Ser His Leu Cys Leu Ile Lys

3470 3475 3480

Pro Gly Gly Lys Gly Phe Thr Cys Glu Cys Pro Asp Asp Phe Arg

3485 3490 3495

Thr Leu Gln Leu Ser Gly Ser Thr Tyr Cys Met Pro Met Cys Ser

3500 3505 3510

Ser Thr Gln Phe Leu Cys Ala Asn Asn Glu Lys Cys Ile Pro Ile

3515 3520 3525

Trp Trp Lys Cys Asp Gly Gln Lys Asp Cys Ser Asp Gly Ser Asp

3530 3535 3540

Glu Leu Ala Leu Cys Pro Gln Arg Phe Cys Arg Leu Gly Gln Phe

3545 3550 3555

Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro Gln Thr Leu Cys Asn

3560 3565 3570

Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu Asp Arg Leu Leu

3575 3580 3585

Cys Glu Asn His His Cys Asp Ser Asn Glu Trp Gln Cys Ala Asn

3590 3595 3600

Lys Arg Cys Ile Pro Glu Ser Trp Gln Cys Asp Thr Phe Asn Asp

3605 3610 3615

Cys Glu Asp Asn Ser Asp Glu Asp Ser Ser His Cys Ala Ser Arg

3620 3625 3630

Thr Cys Arg Pro Gly Gln Phe Arg Cys Ala Asn Gly Arg Cys Ile

3635 3640 3645

Pro Gln Ala Trp Lys Cys Asp Val Asp Asn Asp Cys Gly Asp His

3650 3655 3660

Ser Asp Glu Pro Ile Glu Glu Cys Met Ser Ser Ala His Leu Cys

3665 3670 3675

Asp Asn Phe Thr Glu Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile

3680 3685 3690

Pro Lys Trp Ala Val Cys Asn Gly Val Asp Asp Cys Arg Asp Asn

3695 3700 3705

Ser Asp Glu Gln Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly

3710 3715 3720

Asp Phe Arg Cys Lys Asn His His Cys Ile Pro Leu Arg Trp Gln

3725 3730 3735

Cys Asp Gly Gln Asn Asp Cys Gly Asp Asn Ser Asp Glu Glu Asn

3740 3745 3750

Cys Ala Pro Arg Glu Cys Thr Glu Ser Glu Phe Arg Cys Val Asn

3755 3760 3765

Gln Gln Cys Ile Pro Ser Arg Trp Ile Cys Asp His Tyr Asn Asp

3770 3775 3780

Cys Gly Asp Asn Ser Asp Glu Arg Asp Cys Glu Met Arg Thr Cys

3785 3790 3795

His Pro Glu Tyr Phe Gln Cys Thr Ser Gly His Cys Val His Ser

3800 3805 3810

Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu Asp Ala Ser Asp

3815 3820 3825

Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala Tyr Cys Gln

3830 3835 3840

Ala Thr Met Phe Glu Cys Lys Asn His Val Cys Ile Pro Pro Tyr

3845 3850 3855

Trp Lys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly Ser Asp Glu

3860 3865 3870

Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro Asn Arg

3875 3880 3885

Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val Cys

3890 3895 3900

Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr Glu Glu

3905 3910 3915

His Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr

3920 3925 3930

Lys Cys Gly Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp

3935 3940 3945

Asp Ala Asp Asp Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn

3950 3955 3960

Lys Gly Lys Glu Arg Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn

3965 3970 3975

Cys Thr Gln Leu Asn Glu Gly Gly Phe Ile Cys Ser Cys Thr Ala

3980 3985 3990

Gly Phe Glu Thr Asn Val Phe Asp Arg Thr Ser Cys Leu Asp Ile

3995 4000 4005

Asn Glu Cys Glu Gln Phe Gly Thr Cys Pro Gln His Cys Arg Asn

4010 4015 4020

Thr Lys Gly Ser Tyr Glu Cys Val Cys Ala Asp Gly Phe Thr Ser

4025 4030 4035

Met Ser Asp Arg Pro Gly Lys Arg Cys Ala Ala Glu Gly Ser Ser

4040 4045 4050

Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile Arg Lys Tyr Asn

4055 4060 4065

Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp Glu Glu Tyr

4070 4075 4080

Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro Lys Asp Ile Gly Leu

4085 4090 4095

Ser Val Val Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg Phe Gly

4100 4105 4110

Ala Ile Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser Gly Arg Asn

4115 4120 4125

Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys Tyr Val Met Gln

4130 4135 4140

Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His Ile Tyr Trp

4145 4150 4155

Ser Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu Asp Gly

4160 4165 4170

Arg Tyr Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala

4175 4180 4185

Ala Ile Ala Val Asn Pro Lys Leu Gly Leu Met Phe Trp Thr Asp

4190 4195 4200

Trp Gly Lys Glu Pro Lys Ile Glu Ser Ala Trp Met Asn Gly Glu

4205 4210 4215

Asp Arg Asn Ile Leu Val Phe Glu Asp Leu Gly Trp Pro Thr Gly

4220 4225 4230

Leu Ser Ile Asp Tyr Leu Asn Asn Asp Arg Ile Tyr Trp Ser Asp

4235 4240 4245

Phe Lys Glu Asp Val Ile Glu Thr Ile Lys Tyr Asp Gly Thr Asp

4250 4255 4260

Arg Arg Val Ile Ala Lys Glu Ala Met Asn Pro Tyr Ser Leu Asp

4265 4270 4275

Ile Phe Glu Asp Gln Leu Tyr Trp Ile Ser Lys Glu Lys Gly Glu

4280 4285 4290

Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys Lys Glu Lys Thr

4295 4300 4305

Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile Phe His Gln

4310 4315 4320

Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys Gln Ile Cys

4325 4330 4335

Ser His Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser Cys Ala Cys

4340 4345 4350

Pro Gln Gly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu Cys Asp

4355 4360 4365

Ala Ala Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro Cys Arg Cys

4370 4375 4380

Met His Gly Gly Asn Cys Tyr Phe Asp Glu Thr Asp Leu Pro Lys

4385 4390 4395

Cys Lys Cys Pro Ser Gly Tyr Thr Gly Lys Tyr Cys Glu Met Ala

4400 4405 4410

Phe Ser Lys Gly Ile Ser Pro Gly Thr Thr Ala Val Ala Val Leu

4415 4420 4425

Leu Thr Ile Leu Leu Ile Val Val Ile Gly Ala Leu Ala Ile Ala

4430 4435 4440

Gly Phe Phe His Tyr Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu

4445 4450 4455

Pro Lys Leu Pro Ser Leu Ser Ser Leu Val Lys Pro Ser Glu Asn

4460 4465 4470

Gly Asn Gly Val Thr Phe Arg Ser Gly Ala Asp Leu Asn Met Asp

4475 4480 4485

Ile Gly Val Ser Gly Phe Gly Pro Glu Thr Ala Ile Asp Arg Ser

4490 4495 4500

Met Ala Met Ser Glu Asp Phe Val Met Glu Met Gly Lys Gln Pro

4505 4510 4515

Ile Ile Phe Glu Asn Pro Met Tyr Ser Ala Arg Asp Ser Ala Val

4520 4525 4530

Lys Val Val Gln Pro Ile Gln Val Thr Val Ser Glu Asn Val Asp

4535 4540 4545

Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu Ile Val Pro

4550 4555 4560

Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln Val Thr

4565 4570 4575

Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr Asn Phe

4580 4585 4590

Glu Asn Pro Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu Ser

4595 4600 4605

Val Ala Ala Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala Lys Pro

4610 4615 4620

Lys Pro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr Ser Ala Thr

4625 4630 4635

Glu Asp Thr Phe Lys Asp Thr Ala Asn Leu Val Lys Glu Asp Ser

4640 4645 4650

Glu Val

4655

<210> 941

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 941

cctaaggtta agtcgccctc g 21

<210> 942

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 942

cgagggcgac ttaaccttag g 21

<210> 943

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 943

ccctcagaga cctgagctct t 21

<210> 944

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 944

aagagctcag gtctctgagg g 21

<210> 945

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 945

cctgtaataa acactactct t 21

<210> 946

<211> 21

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 946

aagagtagtg tttattacag g 21

<210> 947

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 947

ccuaagguua agucgcccuc g 21

<210> 948

<211> 19

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 948

ugguuuacau guuguguga 19

<210> 949

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 949

gggcucuagg uuuggugcua ucaaa 25

<210> 950

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 950

ggacugauag gagagucauu gcaaa 25

<210> 951

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 951

ccuguaauaa acacuacucu u 21

<210> 952

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 952

ccuucuauga accuggccuu a 21

<210> 953

<211> 19

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 953

gugauuugau uauacggca 19

<210> 954

<211> 19

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 954

ccucaaaugg cuguagcaa 19

<210> 955

<211> 25

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 955

gaacugacaa gaaacugcgc aacug 25

<210> 956

<211> 21

<212> RNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<400> 956

cccucagaga ccugagcucu u 21

<210> 957

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 957

caguugcgca guuucuuguc aguuctt 27

<210> 958

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 958

caguugcgca guuucuuguc aguuctt 27

<210> 959

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 959

caguugcgca guuucuuguc aguuctt 27

<210> 960

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 960

caguugcgca guuucuuguc aguuctt 27

<210> 961

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 961

aagagcucag gucucugagg gtt 23

<210> 962

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 962

aagagcucag gucucugagg gtt 23

<210> 963

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 963

aagagcucag gucucugagg gtt 23

<210> 964

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 964

uuugauagca ccaaaccuag agccctt 27

<210> 965

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 965

uuugauagca ccaaaccuag agccctt 27

<210> 966

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 966

uuugauagca ccaaaccuag agccctt 27

<210> 967

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 967

uuugauagca ccaaaccuag agccctt 27

<210> 968

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 968

uuugauagca ccaaaccuag agccctt 27

<210> 969

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 969

uuugcaauga cucuccuauc agucctt 27

<210> 970

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 970

uuugcaauga cucuccuauc agucctt 27

<210> 971

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 971

uuugcaauga cucuccuauc agucctt 27

<210> 972

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 972

uuugcaauga cucuccuauc agucctt 27

<210> 973

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 973

ttgucaacgc gucaaagaac agucaag 27

<210> 974

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 974

ttgucaacgc gucaaagaac agucaag 27

<210> 975

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 975

ttgucaacgc gucaaagaac agucaag 27

<210> 976

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 976

ttgucaacgc gucaaagaac agucaag 27

<210> 977

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 977

ttgucaacgc gucaaagaac agucaag 27

<210> 978

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 978

ttgucaacgc gucaaagaac agucaag 27

<210> 979

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 979

ttuucucgag uccagagacu ccc 23

<210> 980

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 980

ttuucucgag uccagagacu ccc 23

<210> 981

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 981

ttuucucgag uccagagacu ccc 23

<210> 982

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 982

ttuucucgag uccagagacu ccc 23

<210> 983

<211> 23

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 983

ttuucucgag uccagagacu ccc 23

<210> 984

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 984

ttaaacuauc gugguuugga ucucggg 27

<210> 985

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 985

ttaaacuauc gugguuugga ucucggg 27

<210> 986

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 986

ttaaacuauc gugguuugga ucucggg 27

<210> 987

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 987

ttaaacuauc gugguuugga ucucggg 27

<210> 988

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 988

ttaaacuguc gugguuugga ucucggg 27

<210> 989

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 989

ttaaacuguc gugguuugga ucucggg 27

<210> 990

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 990

ttaaacuauc gugguuugga ucucggg 27

<210> 991

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 991

ttaaacguua cugagaggau agucagg 27

<210> 992

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 992

ttaaacguua cugagaggau agucagg 27

<210> 993

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 993

ttaaacguua cugagaggau agucagg 27

<210> 994

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 994

ttaaacguua cugagaggau agucagg 27

<210> 995

<211> 27

<212> DNA

<213> Artificial Sequence

<220>

<223> Description of Artificial Sequence: Synthetic

oligonucleotide

<220>

<223> Description of Combined DNA/RNA Molecule: Synthetic

oligonucleotide

<400> 995

ttaaacguua cugagaggau agucagg 27

<210> 996

<211> 23

<212> DNA

<213> Homo sapiens

<400> 996

tgcgcgtgcg cagggataag aga 23

<210> 997

<211> 23

<212> DNA

<213> Homo sapiens

<400> 997

cgcgtgcgca gggataagag agc 23

<210> 998

<211> 23

<212> DNA

<213> Homo sapiens

<400> 998

gcgccgctgt ggggacagca tga 23

<210> 999

<211> 23

<212> DNA

<213> Homo sapiens

<400> 999

cagcatgagc ggcggttgga tgg 23

<210> 1000

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1000

ccgccgcgag cccgctttcc acc 23

<210> 1001

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1001

ctcgtgccca cccaccaagt tcc 23

<210> 1002

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1002

gtgcccaccc accaagttcc agt 23

<210> 1003

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1003

gcccacccac caagttccag tgc 23

<210> 1004

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1004

cagtgccgca ccagtggctt atg 23

<210> 1005

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1005

ccgcaccagt ggcttatgcg tgc 23

<210> 1006

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1006

gcgctgcgac agggacttgg act 23

<210> 1007

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1007

cagcgatggc agcgatgagg agg 23

<210> 1008

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1008

cccctgcacc ggcgtcagtg act 23

<210> 1009

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1009

ctgctctggg ggaactgaca aga 23

<210> 1010

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1010

ctctggggga actgacaaga aac 23

<210> 1011

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1011

tgggggaact gacaagaaac tgc 23

<210> 1012

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1012

gaactgacaa gaaactgcgc aactg 25

<210> 1013

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1013

cacgctgagc gatgactgca ttc 23

<210> 1014

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1014

acgctgagcg atgactgcat tcc 23

<210> 1015

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1015

ctgagcgatg actgcattcc act 23

<210> 1016

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1016

gagcgatgac tgcattccac tca 23

<210> 1017

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1017

tgcgacggcc acccagactg tcc 23

<210> 1018

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1018

gagctcggct gtggaaccaa tga 23

<210> 1019

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1019

tcggctgtgg aaccaatgag atc 23

<210> 1020

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1020

cggctgtgga accaatgaga tcc 23

<210> 1021

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1021

ctgtggaacc aatgagatcc tcc 23

<210> 1022

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1022

tggagagtgt cacctctctc agg 23

<210> 1023

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1023

ctctcaggaa tgccacaacc atg 23

<210> 1024

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1024

tcccctctgt cgggaatgcc aca 23

<210> 1025

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1025

ctgtcgggaa tgccacatcc tcc 23

<210> 1026

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1026

ctgccggaga ccagtctgga agc 23

<210> 1027

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1027

cccaactgcc tatggggtta ttg 23

<210> 1028

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1028

ctgctgcggt gctcagtgca agc 23

<210> 1029

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1029

caccgccacc ctcctccttt tgt 23

<210> 1030

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1030

ccgccaccct cctccttttg tcc 23

<210> 1031

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1031

ccgcccactg gggttactgg tgg 23

<210> 1032

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1032

ggggttactg gtggccatga agg 23

<210> 1033

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1033

tactggtggc catgaaggag tcc 23

<210> 1034

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1034

gagtccctgc tgctgtcaga aca 23

<210> 1035

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1035

ccctgctgct gtcagaacag aag 23

<210> 1036

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1036

tgctgctgtc agaacagaag acc 23

<210> 1037

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1037

tgctgtcaga acagaagacc tcg 23

<210> 1038

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1038

acctcgctgc cctgaggaca agc 23

<210> 1039

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1039

ctgccctgag gacaagcact tgc 23

<210> 1040

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1040

gagcagtgat gcggatgggt acc 23

<210> 1041

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1041

gggcacacca gccctcagag acc 23

<210> 1042

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1042

ccctcagaga cctgagctct tct 23

<210> 1043

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1043

ctcagagacc tgagctcttc tgg 23

<210> 1044

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1044

gggtccctgg acactcccta tgg 23

<210> 1045

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1045

tccctggaca ctccctatgg aga 23

<210> 1046

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1046

ctggacactc cctatggaga tcc 23

<210> 1047

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1047

acctgccaca gccagaactg agg 23

<210> 1048

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1048

ggcagctccc agggggtaga acg 23

<210> 1049

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1049

gggtagaacg gccctgtgct taa 23

<210> 1050

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1050

aacggccctg tgcttaagac act 23

<210> 1051

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1051

cggccctgtg cttaagacac tcc 23

<210> 1052

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1052

ttgcttcaca tcctcaaaaa aaa 23

<210> 1053

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1053

tgcttcacat cctcaaaaaa aaa 23

<210> 1054

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1054

gtcaagattg ctcacaaagt aca 23

<210> 1055

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1055

gtcagtgtat cccaagtgaa tac 23

<210> 1056

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1056

ttgcacaatg agttttcatg tgg 23

<210> 1057

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1057

tggagaagat gactgtaaag ata 23

<210> 1058

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1058

gagaagatga ctgtaaagat aat 23

<210> 1059

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1059

ctcatgatgt tcataaatgt tcc 23

<210> 1060

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1060

ctccatttat aaagtttgtg atg 23

<210> 1061

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1061

tccatttata aagtttgtga tgg 23

<210> 1062

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1062

taccggaaaa tactgtagta tga 23

<210> 1063

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1063

ccggaaaata ctgtagtatg act 23

<210> 1064

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1064

tgccagatat ggggaatttg tga 23

<210> 1065

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1065

ctgtgaagaa gggtatatct tgg 23

<210> 1066

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1066

tggacagtat tgcaaagcta atg 23

<210> 1067

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1067

cagtattgca aagctaatga ttc 23

<210> 1068

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1068

tgcaaagcta atgattcctt tgg 23

<210> 1069

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1069

ttgttaattg gtgatattca tgg 23

<210> 1070

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1070

ccgtgcaaaa taaggttttt tca 23

<210> 1071

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1071

gtgcaaaata aggttttttc agt 23

<210> 1072

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1072

aaggtttttt cagttgacat taa 23

<210> 1073

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1073

aggttttttc agttgacatt aat 23

<210> 1074

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1074

cagttgacat taatggttta aat 23

<210> 1075

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1075

ttgacattaa tggtttaaat atc 23

<210> 1076

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1076

ctgggttaat aataaaatct atc 23

<210> 1077

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1077

tgggttaata ataaaatcta tct 23

<210> 1078

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1078

ccgcatagat atggtaaatt tgg 23

<210> 1079

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1079

tacccttata actgaaaact tgg 23

<210> 1080

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1080

cccaactgtt ggttatttat ttt 23

<210> 1081

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1081

ctgttggtta tttatttttc tca 23

<210> 1082

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1082

gggtaactct ggatatgata tcg 23

<210> 1083

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1083

cggtttgatt acattgaaac tgt 23

<210> 1084

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1084

ttgattacat tgaaactgta act 23

<210> 1085

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1085

tacattgaaa ctgtaactta tga 23

<210> 1086

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1086

tgctaccaat ccgtgtaaag ata 23

<210> 1087

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1087

ttctttgtcg ggattgattt tga 23

<210> 1088

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1088

cagcactatc tttttttcag ata 23

<210> 1089

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1089

agcactatct ttttttcaga tat 23

<210> 1090

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1090

atgtcaaaac acatgatttt taa 23

<210> 1091

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1091

aacacatgat ttttaagcaa aag 23

<210> 1092

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1092

gggtggaaaa tgttgaaagt ttg 23

<210> 1093

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1093

tggcttttga ttggatttca aag 23

<210> 1094

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1094

ggcttttgat tggatttcaa aga 23

<210> 1095

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1095

ttggatttca aagaatctct att 23

<210> 1096

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1096

tggatttcaa agaatctcta ttg 23

<210> 1097

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1097

cacagtagtt cagtatttaa ata 23

<210> 1098

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1098

cagtagttca gtatttaaat aac 23

<210> 1099

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1099

atccttttgc cgggtatcta ttc 23

<210> 1100

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1100

tgggtagatg cctattttga taa 23

<210> 1101

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1101

tgcctatttt gataaaattg agc 23

<210> 1102

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1102

gccatctttg gagagcattt att 23

<210> 1103

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1103

ttgcttacat actgcatttg aaa 23

<210> 1104

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1104

tgcttacata ctgcatttga aat 23

<210> 1105

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1105

tggttctaac gcctgtaatc aac 23

<210> 1106

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1106

tcgatgattg tcatgataac agt 23

<210> 1107

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1107

cacccaatac acctgtgata atc 23

<210> 1108

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1108

acccaataca cctgtgataa tca 23

<210> 1109

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1109

accagtgtat ctcaaagaac tgg 23

<210> 1110

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1110

atgaaaagaa ctgcaattcg aca 23

<210> 1111

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1111

ccccaatcat cgatgtattg acc 23

<210> 1112

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1112

tcgatgtatt gacctatcgt ttg 23

<210> 1113

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1113

atgtattgac ctatcgtttg tct 23

<210> 1114

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1114

tcgttgtgat ggtgtttttg att 23

<210> 1115

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1115

cccgaacttc tgggaatgtg atg 23

<210> 1116

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1116

ccgaacttct gggaatgtga tgg 23

<210> 1117

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1117

cccaagactt gcccttcatc ata 23

<210> 1118

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1118

ttcttacttg ccaatgattc taa 23

<210> 1119

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1119

aagacataga tgaatgtgat att 23

<210> 1120

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1120

gacatagatg aatgtgatat tct 23

<210> 1121

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1121

gtgtgataca ggctacatgt tag 23

<210> 1122

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1122

aggctacatg ttagaaagtg atg 23

<210> 1123

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1123

ggctacatgt tagaaagtga tgg 23

<210> 1124

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1124

gtcgagaatg gttcttacat tgt 23

<210> 1125

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1125

gagaatggtt cttacattgt agc 23

<210> 1126

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1126

tacattgtag ctgttgattt tga 23

<210> 1127

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1127

agctgttgat tttgattcaa tta 23

<210> 1128

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1128

ctgttgattt tgattcaatt agt 23

<210> 1129

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1129

ttcaattagt ggtcgtatct ttt 23

<210> 1130

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1130

agcatcatct tgactgaaac tat 23

<210> 1131

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1131

atcatcttga ctgaaactat tgc 23

<210> 1132

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1132

ttgactgaaa ctattgcaat aga 23

<210> 1133

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1133

gactgaaact attgcaatag att 23

<210> 1134

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1134

ctgaaactat tgcaatagat tgg 23

<210> 1135

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1135

aacaattgaa gtctccaaaa ttg 23

<210> 1136

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1136

tgctgattag taaaaaccta aca 23

<210> 1137

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1137

tagcattaga tcccagaatg aat 23

<210> 1138

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1138

agcattagat cccagaatga atg 23

<210> 1139

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1139

cagaatgaat gagcatctac tgt 23

<210> 1140

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1140

atggactttt gtgattataa tgg 23

<210> 1141

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1141

gacttttgtg attataatgg aca 23

<210> 1142

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1142

gtgatttgat tatacggca 19

<210> 1143

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1143

gtcagttgta atgtataata ttc 23

<210> 1144

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1144

ttgtaatgta taatattcaa tgg 23

<210> 1145

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1145

atccttcgaa acaaccaaat tcc 23

<210> 1146

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1146

ttcgaaacaa ccaaattccg tga 23

<210> 1147

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1147

aacctttctt aataactgta agg 23

<210> 1148

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1148

aggcaacata taatttttgg aat 23

<210> 1149

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1149

ggcaacatat aatttttgga atc 23

<210> 1150

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1150

agggatacag aatggtttag atg 23

<210> 1151

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1151

gggatacaga atggtttaga tgt 23

<210> 1152

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1152

cagaatggtt tagatgttga att 23

<210> 1153

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1153

tacatctatt gggttgaaaa tcc 23

<210> 1154

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1154

aggacagtat ttgcttctat atc 23

<210> 1155

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1155

cagtatttgc ttctatatct atg 23

<210> 1156

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1156

ccttctatga acctggcctt a 21

<210> 1157

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1157

gccttagatt ggatttcaag aaa 23

<210> 1158

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1158

tggatttcaa gaaaccttta ttc 23

<210> 1159

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1159

ctcagtcaat cgaggttttg aca 23

<210> 1160

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1160

acggagatat cagatacaga aaa 23

<210> 1161

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1161

cggagatatc agatacagaa aaa 23

<210> 1162

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1162

gagatatcag atacagaaaa aca 23

<210> 1163

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1163

cagatacaga aaaacattga ttg 23

<210> 1164

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1164

gtccatgatt ctttccttta tta 23

<210> 1165

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1165

tccatgattc tttcctttat tat 23

<210> 1166

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1166

ttctttcctt tattatactg atg 23

<210> 1167

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1167

aacagtatga ggtcattgaa aga 23

<210> 1168

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1168

ttgagagata atgttccaaa tct 23

<210> 1169

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1169

gagagataat gttccaaatc tga 23

<210> 1170

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1170

gagataatgt tccaaatctg agg 23

<210> 1171

<211> 19

<212> DNA

<213> Homo sapiens

<400> 1171

cctcaaatgg ctgtagcaa 19

<210> 1172

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1172

ctctccatat aactctttca ttg 23

<210> 1173

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1173

tccatataac tctttcattg ttg 23

<210> 1174

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1174

aactctttca ttgttgtttc aat 23

<210> 1175

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1175

ctctttcatt gttgtttcaa tgc 23

<210> 1176

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1176

ctgcaatcag aggctttagc ttg 23

<210> 1177

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1177

tgcaatcaga ggctttagct tgg 23

<210> 1178

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1178

gaggctttag cttggaattg tca 23

<210> 1179

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1179

ggctttagct tggaattgtc aga 23

<210> 1180

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1180

ttggaattgt cagatcattc aga 23

<210> 1181

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1181

tggatcttct ctgatgaaca ttg 23

<210> 1182

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1182

aacattgtga cacatggaat agg 23

<210> 1183

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1183

ttctgaaaca ctgatagaag ttc 23

<210> 1184

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1184

tagaagttct gcggatcaat act 23

<210> 1185

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1185

ttgttgtaga tcccaagaac aga 23

<210> 1186

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1186

accaaagatt gagcgttctt tcc 23

<210> 1187

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1187

ccgaagtgat ggctacgttt att 23

<210> 1188

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1188

tgggttgatg attctttaga tat 23

<210> 1189

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1189

ttgatgattc tttagatata att 23

<210> 1190

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1190

cactgttttt gaaaattcta tca 23

<210> 1191

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1191

ctgtttttga aaattctatc ata 23

<210> 1192

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1192

tgggtagata ggaatttgaa aaa 23

<210> 1193

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1193

gggtagatag gaatttgaaa aag 23

<210> 1194

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1194

cacagtgata agagacaata tca 23

<210> 1195

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1195

cagtgataag agacaatatc aac 23

<210> 1196

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1196

ggcaagaatt gtgccatttc aac 23

<210> 1197

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1197

aagaattgtg ccatttcaac aga 23

<210> 1198

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1198

gtgccatttc aacagaaaat ttc 23

<210> 1199

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1199

tgccatttca acagaaaatt tcc 23

<210> 1200

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1200

ctcatctttg ccttgtctaa ttc 23

<210> 1201

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1201

acctttccaa acaataaatg tgg 23

<210> 1202

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1202

gactatgaca gtgtaagtga tag 23

<210> 1203

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1203

cagtgtaagt gatagaatct act 23

<210> 1204

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1204

gtgtaagtga tagaatctac ttc 23

<210> 1205

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1205

tagaatctac ttcacacaaa att 23

<210> 1206

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1206

atctacttca cacaaaattt agc 23

<210> 1207

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1207

gcctttgact ggattactag aag 23

<210> 1208

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1208

gactggatta ctagaagaat tta 23

<210> 1209

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1209

ctggattact agaagaattt att 23

<210> 1210

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1210

tggattacta gaagaattta tta 23

<210> 1211

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1211

gactctctat ggccagtata ttt 23

<210> 1212

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1212

ctgacttgta cacacaaaga att 23

<210> 1213

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1213

gacttgtaca cacaaagaat tta 23

<210> 1214

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1214

tacacacaaa gaatttaccg agc 23

<210> 1215

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1215

accagaaaca acagtgtaac aat 23

<210> 1216

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1216

cagaaacaac agtgtaacaa tcc 23

<210> 1217

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1217

aacaatcctt gtgaacagtt taa 23

<210> 1218

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1218

gtggacaatg gtgaacgatg tgg 23

<210> 1219

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1219

cggagtttat gtgcaataac aga 23

<210> 1220

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1220

gagtttatgt gcaataacag aag 23

<210> 1221

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1221

tggatacaca aaatgtcata att 23

<210> 1222

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1222

tacacaaaat gtcataattc aaa 23

<210> 1223

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1223

cacaaaatgt cataattcaa ata 23

<210> 1224

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1224

gtcataattc aaatatttgt att 23

<210> 1225

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1225

ttgtattcct cgcgtttatt tgt 23

<210> 1226

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1226

gtgatgaaaa ccctacttat tgc 23

<210> 1227

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1227

tcctcaacat tggtattgtg atc 23

<210> 1228

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1228

tggtattgtg atcaagaaac aga 23

<210> 1229

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1229

gtgatcaaga aacagattgt ttt 23

<210> 1230

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1230

ttccgagttt ctctgtgtaa atg 23

<210> 1231

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1231

tccgagtttc tctgtgtaaa tga 23

<210> 1232

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1232

cggctacgat gagaatcaga att 23

<210> 1233

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1233

aggagaactt gctctgaaaa tga 23

<210> 1234

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1234

gactgtgtat cccaaagata ttc 23

<210> 1235

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1235

gccaacagaa tcagtttacc tgt 23

<210> 1236

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1236

gacaccttaa ccagtttcta ttg 23

<210> 1237

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1237

accttaacca gtttctattg ttc 23

<210> 1238

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1238

gacttgtgtt gatattgatg aat 23

<210> 1239

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1239

atgtaatagg ctcctacatc tgt 23

<210> 1240

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1240

ccggcaaaac agtaacatcg aac 23

<210> 1241

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1241

accctatctc atttttagca acc 23

<210> 1242

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1242

aaccgttact atttgagaaa ttt 23

<210> 1243

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1243

accgttacta tttgagaaat tta 23

<210> 1244

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1244

ccgttactat ttgagaaatt taa 23

<210> 1245

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1245

tactatttga gaaatttaac tat 23

<210> 1246

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1246

ttgagaaatt taactataga tgg 23

<210> 1247

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1247

aactatagat ggctattttt act 23

<210> 1248

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1248

gacaatgttg tggcattaga ttt 23

<210> 1249

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1249

gagaagagat tgtattggat tga 23

<210> 1250

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1250

ggcaagtcat tgagagaatg ttt 23

<210> 1251

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1251

gacaaacaag gagacaatca taa 23

<210> 1252

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1252

aaccaacaag tctgtgataa tct 23

<210> 1253

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1253

ttcgctatta ccatttttga aga 23

<210> 1254

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1254

cgctattacc atttttgaag aca 23

<210> 1255

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1255

cagtggaaaa gggaaacaaa tat 23

<210> 1256

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1256

aacaaatatg atggatcaaa tag 23

<210> 1257

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1257

tccatgtgta ccatccatat agg 23

<210> 1258

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1258

ctgatgaaga ccgtcttctt tgt 23

<210> 1259

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1259

gtgacaactt cacagaattc agc 23

<210> 1260

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1260

cagtgtacaa gtggacattg tgt 23

<210> 1261

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1261

gtgtacaagt ggacattgtg tac 23

<210> 1262

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1262

tactatgttc gaatgcaaaa acc 23

<210> 1263

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1263

atgttcgaat gcaaaaacca tgt 23

<210> 1264

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1264

atgcaaaaac catgtttgta tcc 23

<210> 1265

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1265

ccgccatatt ggaaatgtga tgg 23

<210> 1266

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1266

tggttcagat gaagaacttc acc 23

<210> 1267

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1267

gacaacaatc gctgcattta tag 23

<210> 1268

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1268

cccctaaacc ttgtacagaa tat 23

<210> 1269

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1269

ccctaaacct tgtacagaat atg 23

<210> 1270

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1270

aaccttgtac agaatatgaa tat 23

<210> 1271

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1271

accttgtaca gaatatgaat ata 23

<210> 1272

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1272

ttgtacagaa tatgaatata agt 23

<210> 1273

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1273

ccgatgaact gggttgcaat aaa 23

<210> 1274

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1274

aagaacatgt gctgaaaata tat 23

<210> 1275

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1275

agcaaaattg tacccaatta aat 23

<210> 1276

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1276

gggttcgaaa ccaatgtttt tga 23

<210> 1277

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1277

tcgaaaccaa tgtttttgac aga 23

<210> 1278

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1278

ctgacaatgt ccgaattcga aaa 23

<210> 1279

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1279

gtccgaattc gaaaatataa tct 23

<210> 1280

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1280

ccgaattcga aaatataatc tct 23

<210> 1281

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1281

ctcagagtat cttcaagatg agg 23

<210> 1282

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1282

atcttcaaga tgaggaatat atc 23

<210> 1283

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1283

gggctctagg tttggtgcta tcaaa 25

<210> 1284

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1284

tgcctacatc cccaactttg aat 23

<210> 1285

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1285

aggaagttga cctgaaactg aaa 23

<210> 1286

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1286

gacctgaaac tgaaatacgt aat 23

<210> 1287

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1287

acctgaaact gaaatacgta atg 23

<210> 1288

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1288

acgcattgag gtggctaaac ttg 23

<210> 1289

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1289

tcccaaacta gggcttatgt tct 23

<210> 1290

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1290

gggaaaggaa cctaaaatcg agt 23

<210> 1291

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1291

ccgcaacatc ctggttttcg agg 23

<210> 1292

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1292

gcctttctat cgattatttg aac 23

<210> 1293

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1293

ttctatcgat tatttgaaca atg 23

<210> 1294

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1294

aggacgttat tgaaaccata aaa 23

<210> 1295

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1295

gacgttattg aaaccataaa ata 23

<210> 1296

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1296

acgttattga aaccataaaa tat 23

<210> 1297

<211> 25

<212> DNA

<213> Homo sapiens

<400> 1297

ggactgatag gagagtcatt gcaaa 25

<210> 1298

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1298

accagttata ctggatatct aag 23

<210> 1299

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1299

gggagaagta tggaaacaaa ata 23

<210> 1300

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1300

aagtatggaa acaaaataaa ttt 23

<210> 1301

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1301

ttcatcaact cagatacaat aag 23

<210> 1302

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1302

cggaggaaat tgctattttg atg 23

<210> 1303

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1303

aggaaattgc tattttgatg aga 23

<210> 1304

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1304

caccggaaaa tattgtgaaa tgg 23

<210> 1305

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1305

ttgtgaaatg gcgttttcaa aag 23

<210> 1306

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1306

caggattctt ccactataga agg 23

<210> 1307

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1307

ggcagatctt aacatggata ttg 23

<210> 1308

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1308

ggcaatgagt gaagactttg tca 23

<210> 1309

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1309

atctgaaaat gtggataata aga 23

<210> 1310

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1310

ctgaaaatgt ggataataag aat 23

<210> 1311

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1311

gtggataata agaattatgg aag 23

<210> 1312

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1312

tggataataa gaattatgga agt 23

<210> 1313

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1313

tggaatctct tcaaacgaaa atc 23

<210> 1314

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1314

atctcttcaa acgaaaatct aaa 23

<210> 1315

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1315

ctcttcaaac gaaaatctaa aca 23

<210> 1316

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1316

ttcaaacgaa aatctaaaca aac 23

<210> 1317

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1317

aacgaaaatc taaacaaact acc 23

<210> 1318

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1318

aacaaactac caactttgaa aat 23

<210> 1319

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1319

taccaacttt gaaaatccaa tct 23

<210> 1320

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1320

aactttgaaa atccaatcta tgc 23

<210> 1321

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1321

tgcaacagaa gacactttta aag 23

<210> 1322

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1322

caccgcaaat cttgttaaag aag 23

<210> 1323

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1323

cgcaaatctt gttaaagaag act 23

<210> 1324

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1324

ctctgaagta tagctatacc agc 23

<210> 1325

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1325

accagctatt tagggaataa tta 23

<210> 1326

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1326

cagctattta gggaataatt aga 23

<210> 1327

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1327

aacacacttt tgcacatata ttt 23

<210> 1328

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1328

cacacttttg cacatatatt ttt 23

<210> 1329

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1329

tacaaacaga tgaaaaaagt taa 23

<210> 1330

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1330

aagttaacat tcagtacttt atg 23

<210> 1331

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1331

ttcagtactt tatgaaaaaa ata 23

<210> 1332

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1332

cagtacttta tgaaaaaaat ata 23

<210> 1333

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1333

ccgtctcata tttttacaaa taa 23

<210> 1334

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1334

tacaaataat tatcacaatg tac 23

<210> 1335

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1335

atcacaatgt actatatgta tat 23

<210> 1336

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1336

cacaatgtac tatatgtata tct 23

<210> 1337

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1337

atgtactata tgtatatctt tgc 23

<210> 1338

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1338

ctgaagttgt ctgaaggtaa tac 23

<210> 1339

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1339

ctgaaggtaa tactataaat ata 23

<210> 1340

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1340

ttgtaaattt tggaaagatt atc 23

<210> 1341

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1341

tggaaagatt atcctgttac tga 23

<210> 1342

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1342

aagattatcc tgttactgaa ttt 23

<210> 1343

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1343

atcctgttac tgaatttgct aat 23

<210> 1344

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1344

tcctgttact gaatttgcta ata 23

<210> 1345

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1345

tactgaattt gctaataaag atg 23

<210> 1346

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1346

gtgatcatta tagtaaatga tcc 23

<210> 1347

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1347

tagtaaatga tccaacaaga aaa 23

<210> 1348

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1348

tccaacaaga aaaggaattg act 23

<210> 1349

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1349

cactcatatt tcctataaaa tta 23

<210> 1350

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1350

ctcatatttc ctataaaatt atc 23

<210> 1351

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1351

gtccattttt acacattagc act 23

<210> 1352

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1352

tagcacttaa ttaatgttca ata 23

<210> 1353

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1353

agcacttaat taatgttcaa tat 23

<210> 1354

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1354

cacttaatta atgttcaata tta 23

<210> 1355

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1355

ttcaatatta catgtcaatt tga 23

<210> 1356

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1356

ttgattaatg gctatgttga tag 23

<210> 1357

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1357

ggccactatg tgttgtatag aca 23

<210> 1358

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1358

cactatgtgt tgtatagaca tct 23

<210> 1359

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1359

aggtaggaaa agcaattcag ttt 23

<210> 1360

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1360

gccaagacaa catttttatt tgt 23

<210> 1361

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1361

gacaacattt ttatttgtga tgt 23

<210> 1362

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1362

atgaggaaat cccatatcat taa 23

<210> 1363

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1363

tgcattgagt ttgtggttaa tta 23

<210> 1364

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1364

ttgagtttgt ggttaattaa atg 23

<210> 1365

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1365

agctgaattt ctgaaaccaa atc 23

<210> 1366

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1366

accaaatctg tgtcttcata aaa 23

<210> 1367

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1367

tgggtttttg tttctatgaa aat 23

<210> 1368

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1368

ttgtttctat gaaaatatca tta 23

<210> 1369

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1369

ttctatgaaa atatcattat aat 23

<210> 1370

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1370

atgaaaatat cattataatc act 23

<210> 1371

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1371

atcattataa tcactattta ttt 23

<210> 1372

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1372

aaccattctt attaagcttt tta 23

<210> 1373

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1373

accattctta ttaagctttt tat 23

<210> 1374

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1374

gtggctaaat gtgtacattt ata 23

<210> 1375

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1375

tggctaaatg tgtacattta tat 23

<210> 1376

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1376

ggctaaatgt gtacatttat att 23

<210> 1377

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1377

atgtgtacat ttatattaga atg 23

<210> 1378

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1378

cagatctttt ctttaattct tat 23

<210> 1379

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1379

atcttttctt taattcttat tgg 23

<210> 1380

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1380

ttctttaatt cttattggtt ttt 23

<210> 1381

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1381

ctcttaaata gtgggtatag tct 23

<210> 1382

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1382

gtgctaatat tgcacatttg tta 23

<210> 1383

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1383

tgctaatatt gcacatttgt taa 23

<210> 1384

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1384

atggatgaat gaatgaaaca tat 23

<210> 1385

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1385

atgaatgaaa catatactac tga 23

<210> 1386

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1386

atgaaacata tactactgat tat 23

<210> 1387

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1387

aacatatact actgattatt tta 23

<210> 1388

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1388

ctgactgtaa ttactttgat tag 23

<210> 1389

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1389

ctgtaattac tttgattaga taa 23

<210> 1390

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1390

tagataaaca actggaaata atg 23

<210> 1391

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1391

ctgctgaaaa agttctaata aat 23

<210> 1392

<211> 23

<212> DNA

<213> Homo sapiens

<400> 1392

tgctgaaaaa gttctaataa atg 23

<210> 1393

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1393

ccctcagaga cctgagctct t 21

<210> 1394

<211> 21

<212> DNA

<213> Homo sapiens

<400> 1394

cctgtaataa acactactct t 21

Claim (modification according to treaty 19)

1. A double-stranded RNA interference (RNAi) agent comprising:

(i) A first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a CD320 gene, wherein the first dsRNA comprises a duplex-forming sense strand and an antisense strand, (ii) a second dsRNA for inhibiting expression of an LRP2 gene, wherein the second dsRNA comprises a duplex-forming sense strand and an antisense strand, and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA, and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA.

2. The double stranded RNAi agent of claim 1, wherein (i) said antisense strand of said first dsRNA comprises a region of complementarity to a CD320 RNA transcript.

3. The double stranded RNAi agent of claim 1, wherein (i) said sense strand of said first dsRNA is selected from CD320 of table 5.

4. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 16-30 nucleotide pairs in length.

5. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA or (ii) the second dsRNA comprises a duplex region of 21-23 nucleotide pairs in length.

6. The double stranded RNAi agent of claim 1, wherein at least one strand of (i) the first dsRNA or (ii) the second dsRNA comprises a 3' overhang of at least 2 nucleotides.

7. The double stranded RNAi agent of claim 1, wherein (i) said antisense strand of said first dsRNA comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

AUCCAACCGCCGCUCAUGCUG[dT][dT](SEQ ID NO:4)；

ACUGGAACUUGGUGGGUGGGC[dT][dT](SEQ ID NO:8)；

UCCUCAUCGCUGCCAUCGCUG[dT][dT](SEQ ID NO:12)；

AGUUUCUUGUCAGUUCCCCCA[dT][dT](SEQ ID NO:16)；

UUCCAGACUGGUCUCCGGCAG[dT][dT](SEQ ID NO:48)；

ACAAAAGGAGGAGGGUGGCGG[dT][dT](SEQ ID NO:52)；

UCUGUUCUGACAGCAGCAGGG[dT][dT](SEQ ID NO:57)；

UCUCUGAGGGCUGGUGUGCCC[dT][dT](SEQ ID NO:63)；

AGUGUCUUAAGCACAGGGCCG[dT][dT](SEQ ID NO:91)；

UUUUUUUGAGGAUGUGAAGCA [ dT ] [ dT ] (SEQ ID NO: 93); and

8. The double stranded RNAi agent of claim 1, wherein (i) said antisense strand of said first dsRNA comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

AAGAGCUCAGGUCUCUGAGGGdTdT(SEQ ID NO 64)；

AAGAGCUCAGGUCUCUGAGGGdT*dT(SEQ ID NO 65)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmG mGdT*dT(SEQ ID NO 66)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmG mG(SEQ ID NO 68)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmGdT*dT(SEQ ID NO 71)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmG(SEQ ID NO 72)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 75)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fG(SEQ ID NO 76)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fG(SEQ ID NO 77)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 78)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 79)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fC2fU2fG2fA2fG2fG2fG(SEQ ID NO 81)；

9. The double stranded RNAi agent of claim 1, wherein (i) the sense strand of the first dsRNA is no more than 30 nucleotides in length and (i) the antisense strand of the first dsRNA is no more than 30 nucleotides in length.

10. The double stranded RNAi agent of claim 1, wherein (ii) the antisense strand of the second dsRNA comprises a region of complementarity to an LRP2 RNA transcript.

11. The double stranded RNAi agent of claim 1, wherein (ii) the antisense strand and the sense strand of the second dsRNA are selected from LRP2 of table 6.

12. The double stranded RNAi agent of claim 1, wherein the antisense strand of (ii) the second dsRNA comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

AAUAAAUAACCAACAGUUGGG[dT][dT](SEQ ID NO:213)；

UUUAAAUACUGAACUACUGUG[dT][dT](SEQ ID NO:230)；

AAUCUAUUGCAAUAGUUUCAG[dT][dT](SEQ ID NO:268)；

AUUGAAACAACAAUGAAAGAG[dT][dT](SEQ.ID NO:309)；

UUUUCAAAUUCCUAUCUACCC[dT][dT](SEQ ID NO:327)；

AAUCCAAUACAAUCUCUUCUC[dT][dT](SEQ ID NO:383)；

ACACAAUGUCCACUUGUACAC[dT][dT](SEQ ID NO:395)；

UAUUCUGUACAAGGUUUAGGG[dT][dT](SEQ ID NO:403)；

AUUUUAUAGGAAAUAUGAGUG[dT][dT](SEQ ID NO:517)；

UAUAAAUGUACACAUUUAGCC [ dT ] [ dT ] (SEQ ID NO: 544); and

13. The double stranded RNAi agent of claim 1, wherein the antisense strand of (ii) the second dsRNA comprises a nucleotide sequence (5 '→3') selected from the group consisting of:

UUUGCAAUGACUCUCCUAUCAGUCCdTdT(SEQ ID NO:448)；

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmCdT*dT(SEQ ID NO:450)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmC(SEQ ID NO:452)；

2fUmU2fUmG2fCmA2fAmU2fGmA2fCmU2fCmU2fCmC2fUmA2fUm C2fAmG2fUmC2fCdT*dT(SEQ ID NO:459)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU(SEQ ID NO:464)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fC2fU2fA2fU2fC2fA2fG2fU(SEQ ID NO:465)；

14. The double stranded RNAi agent of claim 1, wherein (ii) the sense strand of the second dsRNA is no more than 30 nucleotides in length and the antisense strand is no more than 30 nucleotides in length.

15. The double stranded RNAi agent of claim 1, comprising (iii): (i) A combination of the first dsRNA and (ii) the second dsRNA.

16. The double stranded RNAi agent of claim 15, wherein (i) said antisense strand of said first dsRNA is selected from the group consisting of:

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

AAGAGCUCAGGUCUCUGAGGGdTdT (SEQ ID NO 64); and

AAGAGCUCAGGUCUCUGAGGGdT x dT (SEQ ID NO 65); and

(Ii) The antisense strand of the second dsRNA is selected from the group consisting of:

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

UUUGCAAUGACUCUCCUAUCAGUCCdTdT (SEQ ID NO: 448); and

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

Wherein is a phosphorothioate linkage; and

17. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA has a duplex structure of (SEQ ID NOs: 4 and 97) or (SEQ ID NOs: 8 and 101).

18. The double stranded RNAi agent of claim 1, wherein (ii) the second dsRNA has a duplex structure of (SEQ ID NOs: 213 and 587) or (SEQ ID NOs: 230 and 604).

19. An isolated cell comprising the double stranded RNAi agent of claim 1.

20. A pharmaceutical composition for inhibiting expression of the CD320 gene, the pharmaceutical composition comprising the double stranded RNAi agents (i) and (ii) of claim 1.

21. A pharmaceutical composition for inhibiting expression of LRP2 gene, the composition comprising double stranded RNAi agents (i) and (ii) of claim 1.

22. The pharmaceutical composition of claim 20, further comprising an excipient.

23. The pharmaceutical composition of claim 21, further comprising an excipient.

24. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with an amount of a CD320 inhibitor effective to inhibit proliferation of the CC.

25. The method of claim 24, wherein the CC expresses CD320.

26. The method of claim 24, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular cancer, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

27. The method of claim 24, wherein the inhibitor is selected from the group consisting of an antibody that binds to CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid encoding CD 320.

28. A method for treating a treatment-resistant cancer in a subject previously treated, comprising administering to the subject an inhibitor of CD320 in an amount effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

29. The method of claim 28, wherein the CC expresses CD320.

30. The method of claim 28, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular cancer, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

31. The method of claim 28, wherein the inhibitor is selected from the group consisting of an antibody that binds to CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

32. A method for treating cancer in a subject having recurrent cancer or recurrent cancer, comprising administering to the subject an inhibitor of CD320 in an amount effective to inhibit or kill CC in the cancer.

33. The method of claim 32, wherein the CC expresses CD320.

34. The method of claim 32, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular cancer, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

35. The method of claim 32, wherein the inhibitor is selected from the group consisting of an antibody that binds to CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

36. The method of any one of claims 27, 31 and 35, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of antifolates, epigenetic modulators, or small molecules with CD320 function or protein inhibitors such as antibodies in combination with an RNAi agent that hybridizes to mRNA encoding CD 320.

37. The method of any one of claims 27, 31, and 35, wherein the method further comprises administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding CD 320.

38. The method of any one of claims 27, 31 and 35, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of antifolates, epigenetic modulators (e.g., HDAC inhibitors) or small molecules or protein inhibitors with CD320 function, such as antibodies, in combination with an RNAi agent that hybridizes to mRNA encoding CD 320.

39. The method of any one of claims 27, 31 and 35, wherein the method further comprises administering metformin in combination with RNAi agents that hybridize to mRNA encoding CD 320.

40. The method of any one of claims 27, 31 and 35, wherein the RNAi agent comprises the antisense strand of table 5.

41. The method of any one of claims 27, 31 and 35, wherein the method further comprises administering an RNAi agent that hybridizes to mRNA encoding LRP2 in combination with the RNAi agent that hybridizes to a nucleic acid sequence encoding CD 320.

42. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with an inhibitor of LRP2 in an amount effective to inhibit proliferation of the CC.

43. The method of claim 42, wherein the CC expresses LRP2.

44. The method of claim 42, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular carcinoma, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

45. The method of claim 42, wherein the inhibitor is selected from the group consisting of an antibody that binds to LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

46. A method for treating a treatment-resistant cancer in a subject previously treated, comprising administering to the subject an inhibitor of LRP2 in an amount effective to inhibit or kill Cancer Cells (CCs) present in the treatment-resistant cancer.

47. The method of claim 46, wherein the CC expresses LRP2.

48. The method of claim 46, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular cancer, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

49. The method of claim 46, wherein the inhibitor is selected from the group consisting of an antibody that binds to LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

50. A method for treating cancer in a subject having recurrent cancer or recurrent cancer, comprising administering to the subject an inhibitor of LRP2 in an amount effective to inhibit or kill CC in the cancer.

51. The method of claim 50, wherein the CC expresses LRP2.

52. The method of claim 50, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, hepatocellular cancer, renal cancer, pancreatic cancer, ovarian cancer, and prostate cancer.

53. The method of any one of claims 42, 46 and 50, wherein the inhibitor is selected from the group consisting of an antibody that binds LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP 2.

54. The method of any one of claims 42, 46 and 50, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of antifolates, epigenetic modulators, or small molecules with LRP2 function or protein inhibitors such as antibodies in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

55. The method of any one of claims 42, 46 and 50, wherein the method further comprises administering a cancer therapeutic in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

56. The method of any one of claims 42, 46 and 50, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of antifolates, epigenetic modulators (e.g., HDAC inhibitors), or small molecules or protein inhibitors such as antibodies with LRP2 function in combination with an RNAi agent that hybridizes to mRNA encoding LRP 2.

57. The method of any one of claims 42, 46 and 50, wherein the method further comprises administering metformin in combination with RNAi agents that hybridize to mRNA encoding LRP 2.

58. The method of any one of claims 42, 46 and 50, wherein the RNAi agent comprises an antisense strand and a sense strand from table 6.

59. A method for inhibiting proliferation of a Cancer Cell (CC), comprising contacting the CC with a composition comprising an inhibitor of CD320 and an inhibitor of LRP2 in amounts effective to inhibit proliferation of the CC.

60. The method of claim 59, wherein the CC expresses CD320 and LRP2.

61. The method of claim 59, wherein the CC is from a cancer selected from the group consisting of melanoma, glioblastoma, lung cancer, breast cancer, triple negative breast cancer, kidney cancer, hepatocellular carcinoma, pancreatic cancer, ovarian cancer, and prostate cancer.

62. The method of claim 59, wherein the composition is a mixture comprising: i) A CD320 inhibitor selected from the group consisting of an antibody that binds to CD320, a small molecule inhibitor of CD320, and an RNAi agent that hybridizes to a nucleic acid encoding CD320, and any combination thereof, and ii) an LRP2 inhibitor selected from the group consisting of an antibody that binds to LRP2, a small molecule inhibitor of LRP2, and an RNAi agent that hybridizes to a nucleic acid sequence encoding LRP2, and any combination thereof.

63. The method of any one of claims 62, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of anti-folates and epigenetic modulators.

64. The method of claim 62, wherein the RNAi agent hybridized to the mRNA encoding CD320 comprises a first double-stranded ribonucleic acid (dsRNA) for inhibiting expression of CD320, wherein the first dsRNA comprises a sense strand and an antisense strand, wherein the antisense strand comprises a region complementary to a CD320 RNA transcript, and the RNAi agent hybridized to the mRNA encoding LRP2 comprises a second dsRNA for inhibiting expression of LRP2, wherein the second dsRNA comprises a sense strand and an antisense strand, wherein the antisense strand comprises a region complementary to an LRP2 RNA transcript.

65. The method of claim 64, wherein the antisense strand complementary to CD320 RNA transcript is selected from table 5 and the antisense strand complementary to LRP2 RNA transcript is selected from table 6.

66. A method as in claim 62, further comprising administering a cancer therapeutic selected from the group consisting of antifolate formulations and epigenetic modulators.

67. The method of claim 62, wherein the method further comprises administering a cancer therapeutic selected from the group consisting of immunomodulatory.

68. The method of claim 62, wherein the method further comprises administering metformin.

Claims

1. A double-stranded RNA interference (RNAi) agent comprising:

2. The double stranded RNAi agent of claim 1, wherein (i) said antisense strand of said first dsRNA comprises a region of complementarity to a CD320RNA transcript.

AUCCAACCGCCGCUCAUGCUG[dT][dT](SEQ ID NO:4)；

ACUGGAACUUGGUGGGUGGGC[dT][dT](SEQ ID NO:8)；

UCCUCAUCGCUGCCAUCGCUG[dT][dT](SEQ ID NO:12)；

AGUUUCUUGUCAGUUCCCCCA[dT][dT](SEQ ID NO:16)；

UUCCAGACUGGUCUCCGGCAG[dT][dT](SEQ ID NO:48)；

ACAAAAGGAGGAGGGUGGCGG[dT][dT](SEQ ID NO:52)；

UCUGUUCUGACAGCAGCAGGG[dT][dT](SEQ ID NO:57)；

UCUCUGAGGGCUGGUGUGCCC[dT][dT](SEQ ID NO:63)；

AGUGUCUUAAGCACAGGGCCG[dT][dT](SEQ ID NO:91)；

UUUUUUUGAGGAUGUGAAGCA [ dT ] [ dT ] (SEQ ID NO: 93); and

AAGAGCUCAGGUCUCUGAGGGdTdT(SEQ ID NO 64)；

AAGAGCUCAGGUCUCUGAGGGdT*dT(SEQ ID NO 65)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmG mGdT*dT(SEQ ID NO 66)；

mAmAmGmAmGmCmUmCmAmGmGmUmCmUmCmUmGmAmGmG mG(SEQ ID NO 68)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmGdT*dT(SEQ ID NO 71)；

mA2fAmG2fAmG2fCmU2fCmA2fGmG2fUmC2fUmC2fUmG2fAmG2fGmG(SEQ ID NO 72)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 75)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fG(SEQ ID NO 76)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fG(SEQ ID NO 77)；

mA2fA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 78)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fCmU2fGmA2fGm G2fGdT*dT(SEQ ID NO 79)；

2fAmA2fGmA2fGmC2fUmC2fAmG2fGmU2fCmU2fC2fU2fG2fA2fG2fG2fG(SEQ ID NO 81)；

AAUAAAUAACCAACAGUUGGG[dT][dT](SEQ ID NO:213)；

UUUAAAUACUGAACUACUGUG[dT][dT](SEQ ID NO:230)；

AAUCUAUUGCAAUAGUUUCAG[dT][dT](SEQ ID NO:268)；

AUUGAAACAACAAUGAAAGAG[dT][dT](SEQ.ID NO:309)；

UUUUCAAAUUCCUAUCUACCC[dT][dT](SEQ ID NO:327)；

AAUCCAAUACAAUCUCUUCUC[dT][dT](SEQ ID NO:383)；

ACACAAUGUCCACUUGUACAC[dT][dT](SEQ ID NO:395)；

UAUUCUGUACAAGGUUUAGGG[dT][dT](SEQ ID NO:403)；

AUUUUAUAGGAAAUAUGAGUG[dT][dT](SEQ ID NO:517)；

UAUAAAUGUACACAUUUAGCC [ dT ] [ dT ] (SEQ ID NO: 544); and

UUUGCAAUGACUCUCCUAUCAGUCCdTdT(SEQ ID NO:448)；

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmCdT*dT(SEQ ID NO:450)；

mUmUmUmGmCmAmAmUmGmAmCmUmCmUmCmCmUmAmUmCmAmGmUmCmC(SEQ ID NO:452)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fCmU2fAmU2fCmA2fGmU(SEQ ID NO:464)；

mU2fUmU2fGmC2fAmA2fUmG2fAmC2fUmC2fUmC2fC2fU2fA2fU2fC2fA2fG2fU(SEQ ID NO:465)；

CAGUUGCGCAGUUUCUUGUCAGUUCdTdT(SEQ ID NO:17)；

CAGUUGCGCAGUUUCUUGUCAGUUCdT*dT(SEQ ID NO 18)；

AAGAGCUCAGGUCUCUGAGGGdTdT (SEQ ID NO 64); and

AAGAGCUCAGGUCUCUGAGGGdT x dT (SEQ ID NO 65); and

UUUGAUAGCACCAAACCUAGAGCCCdTdT(SEQ ID NO:417)；

UUUGAUAGCACCAAACCUAGAGCCCdT*dT(SEQ ID NO:418)；

UUUGCAAUGACUCUCCUAUCAGUCCdTdT (SEQ ID NO: 448); and

UUUGCAAUGACUCUCCUAUCAGUCCdT*dT(SEQ ID NO:449)；

Wherein is a phosphorothioate linkage; and

17. The double stranded RNAi agent of claim 1, wherein (i) the first dsRNA has a duplex structure of (SEQ ID NOs: 4 and 7) or (SEQ ID NOs: 8 and 101).

19. An isolated cell comprising the double stranded RNAi agent of claim 1.

25. The method of claim 24, wherein the CC expresses CD320.

29. The method of claim 28, wherein the CC expresses CD320.

33. The method of claim 32, wherein the CC expresses CD320.

43. The method of claim 42, wherein the CC expresses LRP2.

47. The method of claim 46, wherein the CC expresses LRP2.

51. The method of claim 50, wherein the CC expresses LRP2.

60. The method of claim 59, wherein the CC expresses CD320 and LRP2.