EP1572713A2 - Antisense modulation of acyl-coa synthetase 1 expression - Google Patents

Abstract

Antisense compounds, compositions, and methods are provided for modulating the expression of acyl-Coa synthesis 1, heretofore referred to as ACS1. The compositions comprise antisense compounds, particulary antisense oligonucleotides, targeted to nucleic acids encoding ACS1. Methods of using these compounds for modulation of ACS1 expression and for treatment of diseases associated with expression of ACS1 are provided.

Description

Antisense Modulation Of Acyl-CoA Synthetase 1 Expression

The present application claims priority under Title 35, United States Code, §119 to United States Provisional application Serial No. 60/403,591 , filed August 14, 2002, which is incorporated by reference in its entirety as if written herein.

FIELD OF THE INVENTION

[001] The present invention provides compositions and methods for modulating the expression of Acyl-CoA Synthetase 1 (ACSl) also referred to as Fatty Acyl Ligase Isoform 1 (FACL1). In particular, this invention relates to antisense compounds, particularly oligonucleotides, specifically hybridizable with nucleic acids encoding ACSl . Such oligonucleotides have been shown to modulate the expression of acyl-CoA synthetase 1.

BACKGROUND OF THE INVENTION

[002] The initial reaction in synthesizing long chain fatty acids requires ligation to acyl-coenzyme A. ACSl catalyzes the immediate ligation of fatty acids, upon their entry into cells, with coenzyme A (CoA) to produce acyl-CoAs, thereby trapping fatty acids intracellulariy. These acyl-CoA molecules are the main

reactants of β-oxidation are also utilized in reactions such as the synthesis of

triacylglycerol, phospholipids, sphingomyelin, and cholesterol esters. Acyl-CoA's are also the source for several intracellular signaling molecules, most notably ceramide, diacylglycerol, and arachidonic acid. In addition, long-chain acyl-CoA esters have been implicated as physiological regulators of several cellular processes. For example, long-chain acyl-CoA esters negatively regulate enzymes involved in lipid synthesis, such as acetyl-CoA carboxylase (ACC). Acyl-CoA esters are required for ER and Golgi budding and fusion, and ACSl has been found in association with Glut4-containing vesicles in rat adipocytes. There are 5 ACS homologs in humans and rodents, with each showing different tissue distribution (ACS 2 and 3 appear to be CNS-specific) and in some cases, with different subcellular distribution (e.g., ACS 1 , 4 and 5). Table 1 provides the accession numbers for the five ACS isoforms.

Table 1 : Accession Numbers for ACS Isoforms

FACL1 and FA CL2 are the same gene referred to as FA CL2.

[003] ACS 1 , 4 and 5 (found in both liver and adipocytes) also show different degrees of inhibition by triacsin C and thiazolidenediones such as troglitazone (Table 2). Table 2: Regulation by Tracsin C and Thiazolidenediones and Subcellular Localization of ACS Isoforms 1. 4, and 5

MAM = mitochondrially-associated membranes

[004] ACSl expression in liver and adipose provides prima facie evidence that it appears to be a good target for insulin resistance and/or obesity. Recently it has been reported that mice with a homozygous deletion of fatty acid transport protein 1 (FATPl ) fed a high fat diet were prevented from becoming insulin resistant (Jason Kim, J.K. Diabetes 51 Supplement 2, p.A300, abstract #1233P (2002)). Disruption of acyl-CoA synthetase 1 (ACSl), an enzyme that immediately adds acyl-CoA to incoming fatty acids thereby trapping them intracellulariy, would be expected to have a similar phenotype as the FATPl (-/-) mice. Therefore, a loss of function in ACSl would prevent intracellular fatty acid accumulation (at least in liver and adipose) and lead to resistance to high fat diet-induced insulin resistance. In addition to an adipose effect, ACSl inhibition may have effect on plasma lipids by reducing NLDL secretion from liver. Attenuation of cellular diacylglycerol accumulation due to ACSl inhibition may have influence on protein kinase C activity and thereby, in cancer development. In macrophages where triglyceride synthesis is required for esterified cholesterol accumulation, ACSl inhibition may reduce macrophage cholesterol deposit and reduce atherosclerosis. ACS 1 inhibition will have beneficial effect in human disease associated with abnormal fat absorption, lipoprotein secretion and metabolism, and adipogenesis.

[005] Antisense technology is emerging as an effective means for reducing the expression of specific gene products and may therefore prove to be uniquely useful in a number of therapeutic, diagnostic, and research applications for the modulation of ACSl expression.

SUMMARY OF THE INVENTION

[006] The present invention is directed to antisense compounds, particularly oligonucleotides, which are targeted to a nucleic acid encoding

ACSl , and which modulate the expression of ACSl . Pharmaceutical and other compositions comprising the antisense compounds of the invention are also provided. Further provided are methods of modulating the expression of ACSl in cells or tissues comprising contacting said cells or tissues with one or more of the antisense compounds or compositions of the invention. Further provided are methods of treating an animal, particularly a human, suspected of having or being prone to a disease or condition associated with expression of ACSl by administering a therapeutically or prophylactically effective amount of one or more of the antisense compounds or compositions of the invention.

DETAILED DESCRIPTION OF THE INVENTION

[007] The present invention employs oligomeric antisense compounds, particularly oligonucleotides, for use in modulating the function of nucleic acid molecules encoding ACSl , ultimately modulating the amount of ACSl produced. This is accomplished by providing antisense compounds, which specifically hybridize with one or more nucleic acids encoding ACSl. As used herein, the terms "target nucleic acid" and "nucleic acid encoding ACS!" encompass DNA encoding ACSl, RNA (including pre -mRNA and mRNA) transcribed from such DNA, and also cDNA derived from such RNA. The specific hybridization of an oligomeric compound with its target nucleic acid interferes with the normal function of the nucleic acid. This modulation of function of a target nucleic acid by compounds, which specifically hybridize to it, is generally referred to as "antisense". The functions of DNA to be interfered with include replication and transcription. The functions of RNA to be interfered with include all vital functions such as, for example, translocation of the RNA to the site of protein translation, translation of protein from the RNA, splicing of the RNA to yield one or more mRNA species, and catalytic activity which may be engaged in or facilitated by the RNA. The overall effect of such interference with target nucleic acid function is modulation of the expression of ACSl . In the context of the present invention, "modulation" means either an increase (stimulation) or a decrease (inhibition) in the expression of a gene. In the context of the present invention, inhibition is the preferred form of modulation, of gene expression and mRNA is a preferred target. [008] It is preferred to target specific nucleic acids for antisense.

"Targeting" an antisense compound to a particular nucleic acid, in the context of this invention, is a multistep process. The process usually begins with the identification of a nucleic acid sequence whose function is to be modulated. This may be, for example, a cellular gene (or mRNA transcribed from the gene) whose expression is associated with a particular disorder or disease state, or a nucleic acid molecule from an infectious agent. In the present invention, the target is a nucleic acid molecule encoding ACSl . The targeting process also includes determination of a site or sites within this gene for the antisense interaction to occur such that the desired effect, e.g., detection or modulation of expression of the protein, will result. Within the context of the present invention, a preferred intragenic site is the region encompassing the translation initiation or termination codon of the open * reading frame (ORF) of the gene. Since, as is known in the art, the translation initiation codon is typically 5'-AUG (in transcribed mRNA molecules; 5'-ATG in the corresponding DNA molecule), the translation initiation codon is also referred to as the "AUG codon," the "start codon" or the "AUG start codon". A minority of genes have a translation initiation codon having the RNA sequence 5'-GUG, 5'-UUG or 5'-CUG, and 5'- AUA, 5'-ACG and 5'-CUG have been shown to function in vivo. Thus, the terms "translation initiation codon" and "start codon" can encompass many codon sequences, even though the initiator amino acid in each instance is typically methionine (in eukaryotes) or formylmethionine (in prokaryotes). It is also known in the art that eukaryotic and prokaryotic genes may have two or more alternative start codons, any one of which may be preferentially utilized for translation initiation in a particular cell type or tissue, or under a particular set of conditions. In the context of the invention, "start codon" and "translation initiation codon" refer to the codon or codons that are used in vivo to initiate translation of an mRNA molecule transcribed from a gene encoding ACSl , regardless of the sequence(s) of such codons. [009] It is also known in the art that a translation termination codon (or

"stop codon") of a gene may have one of three sequences, i.e. 5'-UAA, 5'- UAG and 5'-UGA (the corresponding DNA sequences are 5'-TAA, 5'-TAG and 5'-TGA, respectively). The terms "start codon region" and "translation initiation codon region "refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation initiation codon. Similarly, the terms "stop codon region" and "translation termination codon region "refer to a portion of such an mRNA or gene that encompasses from about 25 to about 50 contiguous nucleotides in either direction (i.e., 5' or 3') from a translation termination codon. [0010] The open reading frame (ORF) or "coding region," which is known in the art to refer to the region between the translation initiation codon and the translation termination codon, is also a region which may be targeted effectively. Other target regions include the 5' untranslated region (5'UTR), known in the art to refer to the portion of an mRNA in the 5' direction from the translation initiation codon, and thus including nucleotides between the 5' cap site and the translation initiation codon of an mRNA or corresponding nucleotides on the gene, and the 3' untranslated region (3'UTR), known in the art to refer to the portion of an mRNA in the 3' direction from the translation termination codon, and thus including nucleotides between the translation termination codon and 3' end of an mRNA or corresponding nucleotides on the gene. The 5' cap of an mRNA comprises an N7-methylated guanosine residue joined to the 5 '-most residue of the mRNA via a 5'-5' triphosphate linkage. The 5' cap region of an mRNA is considered to include the 5' cap structure itself as well as the first 50 nucleotides adjacent to the cap. The 5' cap region may also be a preferred target region. [0011] Although some eukaryotic mRNA transcripts are directly translated, many contain one or more regions, known as "introns," which are excised from a transcript before it is translated. The remaining (and therefore translated) regions are known as "exons" and are spliced together to form a continuous mRNA sequence. mRNA splice sites, i.e., intron-exon junctions, may also be preferred target regions, and are particularly useful in situations where aberrant splicing is implicated in disease, or where an overproduction of a particular mRNA splice product is implicated in disease. Aberrant fusion junctions due to rearrangements or deletions are also preferred targets. It has also been found that introns can also be effective, and therefore preferred, target regions for antisense compounds targeted, for example, to DNA or pre-mRNA. [0012] Once one or more target sites have been identified, oligonucleotides are chosen which are sufficiently complementary to the target, i.e., hybridize sufficiently well and with sufficient specificity, to give the desired effect.

[0013] In the context of this invention, "hybridization" means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nudeotide bases. For example, adenine and thymine are complementary nucleobases, which pair through the formation of hydrogen bonds. "Complementary," as used herein, refers to the capacity for precise pairing between two nucleotides. For example, if a nudeotide at a certain position of an oligonucleotide is capable of hydrogen bonding with a nudeotide at the same position of a DNA or RNA molecule, then the oligonucleotide and the DNA or RNA are considered to be complementary to each other at that position. The oligonucleotide and the DNA or RNA are complementary to each other when a sufficient number of corresponding positions in each molecule are occupied by nucleotides which can hydrogen bond with each other. Thus, "specifically hybridizable" and "complementary" are terms which are used to indicate a sufficient degree of complementarity or precise pairing such that stable and specific binding occurs between the oligonucleotide and the DNA or RNA target. It is understood in the art that the sequence of an antisense compound need not be 100% complementary to that of its target nucleic acid to be specifically hybridizable. An antisense compound is specifically hybridizable when binding of the compound to the target DNA or RNA molecule interferes with the normal function of the target DNA or RNA to cause a loss of utility, and there is a sufficient degree of complementarity to avoid non-specific binding of the antisense compound to non-target sequences under conditions in which specific binding is desired, i.e., under physiological conditions in the case of in vivo assays or therapeutic treatment, and in the case of in vitro assays, under conditions in which the assays are performed. |0014] Antisense compounds are commonly used as research reagents and diagnostics. For example, antisense oligonucleotides, which are able to inhibit gene expression with exquisite specificity, are often used by those of ordinary skill to elucidate the function of particular genes. Antisense compounds are also used, for example, to distinguish between functions of various members of a biological pathway. Antisense modulation has, therefore, been harnessed for research use. [0015] The specificity and sensitivity of antisense is also harnessed by those of skill in the art for therapeutic uses. Antisense oligonucleotides have been employed as therapeutic moieties in the treatment of disease states in animals and man. Antisense oligonucleotides have been safely and effectively administered to humans and numerous clinical trials are presently underway. It is thus established that oligonucleotides can be useful therapeutic modalities that can be configured to be useful in treatment regimes for treatment of cells, tissues and animals, especially humans. In the context of this invention, the term "oligonucleotide" refers to an oligomer or polymer of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) or mimetics thereof. This term includes oligonucleotides composed of naturally occurring nucleobases, sugars and covalent internucleoside (backbone) linkages as well as oligonucleotides having non-naturally occurring portions which function similarly. Such modified or substituted oligonucleotides are often preferred over native forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic acid target and increased stability in the presence of nucleases. [0016] While antisense oligonucleotides are a preferred form of antisense compound, the present invention comprehends other oligomeric antisense compounds, including but not limited to oligonucleotide mimetics such as are described below. The antisense compounds in accordance with this invention preferably comprise from about 8 to about 30 nucleobases (i.e. from about 8 to about 30 linked nucleo sides). Particularly preferred antisense compounds are antisense oligonucleotides, even more preferably those comprising from about 12 to about 25 nucleobases. As is known in the art, a nucleoside is a base-sugar combination. The base portion of the nucleoside is normally a heterocyclic base. The two most common classes of such heterocyclic bases are the purines and the pyrimidines. Nucleotides are nucleosides that further include a phosphate group covalentiy linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be linked to either the 2', 3' or 5' hydroxyl moiety of the sugar. In forming oligonucleotides, the phosphate groups covalentiy link adjacent nucleosides to one another to form a linear polymeric compound. In turn the respective ends of this linear polymeric structure can be further joined to form a circular structure, however, open linear structures are generally preferred. Within the oligonucleotide structure, the phosphate groups are commonly referred to as forming the internucleoside backbone of the oligonucleotide. The normal linkage or backbone of RNA and DNA is a 3' to 5' phosphodiester linkage. [0017] Specific examples of preferred antisense compounds useful in this invention include oligonucleotides containing modified backbones or non-natural internucleoside linkages. As defined in this specification, oligonucleotides having modified backbones include those that retain a phosphorus atom in the backbone and those that do not have a phosphorus atom in the backbone. For the purposes of this specification, and as sometimes referenced in the art, modified oligonucleotides that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. [0018] Preferred modified oligonucleotide backbones include, for example, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3'alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3 '-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, and boranophosphates having normal 3'-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein the adjacent pairs of nucleoside units are linked 3'-5' to 5'-3' or 2'-5' to 5'-2'. Various salts, mixed salts and free acid forms are also included. [0019] Representative United States patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S. 3,687,808; 4,469,863; 4,476,301 ; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321 ,131 ; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,1 1 1 ; 5,563,253; 5,571 ,799; 5,587,361 ; and 5,625,050, each of which is herein incorporated by reference. [0020] Preferred modified oligonucleotide backbones that do not include a phosphorus atom therein have backbones that are formed by short chain alkyl or cycloalkyl internucleoside linkages, mixed heteroatom and alkyl or cycloalkyl internucleoside linkages, or one or more short chain heteroatomic or heterocyclic internucleoside linkages. These include those having morpholino linkages (formed in part from the sugar portion of a nucleoside); siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH₂ component parts.

[0021] Representative United States patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S. 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141 ; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541 ,307; 5,561 ,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; and 5,677,439, each of which is herein incorporated by reference.

[0022] In other preferred oligonucleotide mimetics, both the sugar and the internucleoside linkage, i.e., the backbone, of the nudeotide units are replaced with novel groups. The base units are maintained for hybridization with an appropriate nucleic acid target compound. One such oligomeric compound, an oligonucleotide mimetic that has been shown to have excellent hybridization properties, is referred to as a peptide nucleic acid (PNA). In PNA compounds, the sugar-backbone of an oligonucleotide is replaced with an amide containing backbone, in particular an aminoethylglycine backbone. The nucleobases are retained and are bound directly or indirectly to aza nitrogen atoms of the amide portion of the backbone. Representative United States patents that teach the preparation of PNA compounds include, but are not limited to, U.S. 5,539,082; 5,714,331 ; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found in Nielsen et al., Science, 1991 , 254, 1497-1500.

[0023] Most preferred embodiments of the invention are oligonucleotides with phosphorothioate backbones and oligonucleosides with heteroatom backbones, and in particular -CH₂-NH-O-CH₂-, -CH₂-N (CH₃) -O-CH₂- [known as a methylene (methylimino) or MMI backbone] , - CH₂-O-N (CH₃) -CH₂-, -CH₂N(CH₃)-N(CH₃)-CH₂- and -O-N(CH₃)-CH₂- CH₂- [wherein the native phosphodiester backbone is represented as -O-P- O-CH2-] of the above referenced U.S. patent 5,489,677, and the amide backbones of the above referenced U.S. patent 5,602,240. Also preferred are oligonucleotides having morpholino backbone structures of the above- referenced U.S. patent 5,034,506.

[0024] Modified oligonucleotides may also contain one or more substituted sugar moieties. Preferred oligonucleotides comprise one of the following at the 2' position: OH; F; O-, S-, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted Ci to Cι₀ alkyl or C₂ to C₁₀ alkenyl and alkynyl. Particularly preferred are O[(CH₂)_nO]_mCH₃, O(CH₂)_n,OCH₃, O(CH₂)_nNH₂, O(CH₂)_nCH₃, O(CH₂)_nONH₂, and O(CH₂nON[(CH2)nCH₃)]2 where n and m are from 1 to about 10. Other preferred oligonucleotides comprise one of the following at the 2' position: C| to C₁₀, (lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH₃, OCN, Cl, Br, CN, CF₃, OCF₃, SOCH₃, SO₂CH₃, ONO₂, NO₂, N₃, NH2, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties of an oligonucleotide, or a group for improving the pharmacodynamic properties of an oligonucleotide, and other substituents having similar properties. A preferred modification includes 2' -methoxyethoxy (2' -O-CH₂CH₂OCH₃, also known as 2'-O- (2- mefhoxyefhyl) or 2'-MOE) (Martin et al., Helv. Chim. Acta, 1995, 78, 486- 504) i.e., an alkoxyalkoxy group. A further preferred modification includes 2'-dimethylaminooxyethoxy, i.e., a O(CH₂)₂ON(CH₃)₂ group, also known as 2'-DMAOE, as described in examples herein below, and 2'- dimethylaminoethoxyethoxy (also known in the art as 2'-O- dimethylaminoethoxyethyl or 2'-DMAEOE), i.e., 2'-O-CH₂-O-CH₂-N (CH₂)2, also described in examples herein below.

[0025] Other preferred modifications include 2'-methoxy (2'-O CH₃), 2'-aminopropoxy (2'-O CH₂ CH₂ CH₂NH₂) and 2 '-fluoro (2'-F). Similar modifications may also be made at other positions on the oligonucleotide, particularly the 3' position of the sugar on the 3' terminal nudeotide or in 2 '-5' linked oligonucleotides and the 5' position of 5' terminal nudeotide. Oligonucleotides may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative United States patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. 4,981,957; 5,1 18,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,81 1 ; 5,576,427; 5,591 ,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920, each of which is herein incorporated by reference in its entirety. [0026] Oligonucleotides may also include nucleobase (often referred to in the art simply as "base") modifications or substitutions. As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uracil (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouracil, 2-thiothymine and 2-thiocytosine, 5- halouracil and cytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracil (pseudouracil), 4-thiouracil, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5- substituted uracils and cytosines, 7-methylquanine and 7-methyladenine, 8- azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine and 3- deazaguanine and 3-deazaadenine. Further nucleobases include those disclosed in United States Patent No. 3,687,808, those disclosed in The Concise Encyclopedia Of Polymer Science And Engineering, pages 858- 859, Kroschwitz, J.I., ed. John Wiley & Sons, 1990, those disclosed by Englisch et al., Angewandte Chemie, International Edition, 1991, 30, 613, and those disclosed by Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, pages 289-302, Crooke, S.T. and Lebleu, B. ed., CRC Press, 1993. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and O-6 substituted purines, including 2-aminopropyladenine, 5 -propynyl uracil and 5-propynylcytosine. 5-methylcytosine substitutions have been shown to increase nucleic acid duplex stability by 0.6-1.2°C (Sanghvi, Y.S., Crooke, S.T. and Lebleu, B., eds, Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2'-O- methoxyethyl sugar modifications.

[0027] Representative United States patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. 3,687,808, as well as U.S.: 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,71 1 ; 5,552,540; 5,587,469; 5,594,121 , 5,596,091 ; 5,614,617; 5,750,692; and 5,681,941, each of which is herein incorporated by reference. [0028] Another modification of the oligonucleotides of the invention involves chemically linking to the oligonucleotide one or more moieties or conjugates, which enhance the activity, cellular distribution or cellular uptake of the oligonucleotide. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989, 86, 6553-6556), cholic acid (Manoharan et al.,

Bioorg. Med. Chem. Let., 1994, 4, 1053-1060), a thioether, e.g., hexyl-S- tritylthiol (Manoharan et al., Ann. N Y. Acad. Sci., 1992, 660, 306-309; Manoharan et al., Bioorg. Med. Chem. Let., 1993, 3, 2765-2770), a thiocholesterol (Oberhauser et al., Nucl. Acids Res., 1992, 20, 533-538), an aliphatic chain, e.g., dodecandiol or undecyl residues (Saison-Behmoaras et al, EMBO J., 1991 , 10, 1 1 11-1 118; Kabanov et al, FEBS Lett., 1990, 259, 327-330; Svinarchuk et al., Biochimie, 1993, 75, 49-54), a phospholipid, e.g., di-hexadecyl-rac-glycerol or triethylammonium 1 ,2-di-O-hexadecyl- rac-glycero-3-H-phosphonate (Manoharan et al., Tetrahedron Lett., 1995, 36, 3651-3654; Shea et al., Nucl. Acids Res., 1990, 18, 3777-3783), a polyamine or a polyethylene glycol chain (Mancharan et al., Nucleosides & Nucleotides, 1995, 14, 969-973), or adamantane acetic acid (Manoharan et al., Tetrahedron Lett., 1995, 36, 365 '-3654), a palmityl moiety (Mishra et al., Biochim. Biophys. Acta, 1995, 1264, 229-237), or an octadecylamine or hexylamino-carbonyl-oxycholesterol moiety (Crooke et al., J. Pharmacol. Exp. Ther., 1996, 277, 923-937).

[0029] Representative United States patents that teach the preparation of such oligonucleotide conjugates include, but are not limited to, U.S.

4,828,979; 4,948,882 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717 5,580,731; 5,580,731 ; 5,591,584; 5,109,124; 5,118,802; 5,138,045 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371 ,241, 5,391 ,723 5,416,203, 5,451 ,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552 5,567,810; 5,574,142; 5,585,481 ; 5,587,371 ; 5,595,726; 5,597,696 5,599,923; 5,599,928 and 5,688,941, each of which is herein incorporated by reference. |0030] It is not necessary for all positions in a given compound to be uniformly modified, and in fact more than one of the aforementioned modifications may be incorporated in a single compound or even at a single nucleoside within an oligonucleotide. The present invention also includes antisense compounds, which are chimeric compounds. "Chimeric" antisense compounds or "chimeras," in the context of this invention, are antisense compounds, particularly oligonucleotides, which contain two or more chemically distinct regions, each made up of at least one monomer unit, i.e., a nudeotide in the case of an oligonucleotide compound. These oligonucleotides typically contain at least one region wherein the oligonucleotide is modified so as to confer upon the oligonucleotide increased resistance to nuclease degradation, increased cellular uptake, and/or increased binding affinity for the target nucleic acid. An additional region of the oligonucleotide may serve as a substrate for enzymes capable of cleaving RNA:DNA or RNA:RNA hybrids. By way of example, RNase H is a cellular endonuclease, which cleaves the RNA strand of RNA:DNA duplex. Activation of RNase H, therefore, results in cleavage of the RNA target, thereby greatly enhancing the efficiency of oligonucleotide inhibition of gene expression. Consequently, comparable results can often be obtained with shorter oligonucleotides when chimeric oligonucleotides are used, compared to phosphorothioate deoxyoligonucleotides hybridizing to the same target region. Cleavage of the RNA target can be routinely detected by gel electrophoresis and, if necessary, associated nucleic acid hybridization techniques known in the art. [0031] Chimeric antisense compounds of the invention may be formed as composite structures of two or more oligonucleotides, modified oligonucleotides, oligonucleosides and/or oligonucleotide mimetics as described above. Such compounds have also been referred to in the art as hybrids or gapmers. Representative United States patents that teach the preparation of such hybrid structures include, but are not limited to, U.S. 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, each of which is herein incorporated by reference in its entirety. [0032] The antisense compounds used in accordance with this invention may be conveniently, and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example, Applied Biosystems (Foster City, CA). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives.

[0033] The antisense compounds of the invention are synthesized in vitro and do not include antisense compositions of biological origin, or genetic vector constructs designed to direct the in vivo synthesis of antisense molecules. The compounds of the invention may also be admixed, encapsulated, conjugated or otherwise associated with other molecules, molecule structures or mixtures of compounds, as for example, liposomes, receptor targeted molecules, oral, rectal, topical or other formulations, for assisting in uptake, distribution and/or absorption. Representative United States patents that teach the preparation of such uptake, distribution and/or absorption assisting formulations include, but are not limited to, U.S. 5,108,921 ; 5,354,844; 5,416,016; 5,459,127; 5,521,291 ; 5,543,158; 5,547,932; 5,583,020; 5,591 ,721 ; 4,426,330; 4,534,899; 5,013,556; 5,108,921 ; 5,213,804; 5,227,170; 5,264,221 ; 5,356,633; 5,395,619; 5,416,016; 5,417,978; 5,462,854; 5,469,854; 5,512,295; 5,527,528; 5,534,259; 5,543,152; 5,556,948; 5,580,575; and 5,595,756, each of which is herein incorporated by reference. [0034] The antisense compounds of the invention encompass any pharmaceutically acceptable salts, esters, or salts of such esters, or any other compound which, upon administration to an animal including a human, is capable of providing (directly or indirectly) the biologically active metabolite or residue thereof. Accordingly, for example, the disclosure is also drawn to prodrugs and pharmaceutically acceptable salts of the compounds of the invention, pharmaceutically acceptable salts of such prodrugs, and other bioequivalents.

[0035] The term "prodrug" indicates a therapeutic agent that is prepared in an inactive form that is converted to an active form (i.e., drug) within the body or cells thereof by the action of endogenous enzymes or other chemicals and/or conditions. In particular, prodrug versions of the oligonucleotides of the invention are prepared as SATE [(S-acetyl-2- thioethyl) phosphate] derivatives according to the methods disclosed in WO 93/24510 to Gosselin et al., published December 9, 1993 or in WO 94/26764 to Imbach et al. [0036] The term "pharmaceutically acceptable salts" refers to physiologically and pharmaceutically acceptable salts of the compounds of the invention: i.e., salts that retain the desired biological activity of the parent compound and do not impart undesired toxicological effects thereto. [0037] Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Examples of metals used as cations are sodium, potassium, magnesium, calcium, and the like. Examples of suitable amines are N, N'- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, dicyclohexylamine, ethylenediamine, N-methylglucamine, and procaine (see, for example, Berge et al., "Pharmaceutical Salts," J. ofPharma Sci., 1977, 66, 1 19). The base addition salts of said acidic compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner. The free acid form may be regenerated by contacting the salt form with an acid and isolating the free acid in the conventional manner. The free acid forms differ from their respective salt forms somewhat in certain physical properties such as solubility in polar solvents, but otherwise the salts are equivalent to their respective free acid for purposes of the present invention. As used herein, a "pharmaceutical addition salt" includes a pharmaceutically acceptable salt of an acid form of one of the components of the compositions of the invention. These include organic or inorganic acid salts of the amines. Preferred acid salts are the hydrochlorides, acetates, salicylates, nitrates and phosphates. Other suitable pharmaceutically acceptable salts are well known to those skilled in the art and include basic salts of a variety of inorganic and organic acids, such as, for example, with inorganic acids, such as for example hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid; with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxymaleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, lactic acid, oxalic acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2- phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid; and with amino acids, such as the 20 alpha-amino acids involved in the synthesis of proteins in nature, for example glutamic acid or aspartic acid, and also with phenylacetic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, ethane- 1,2-disulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfoic acid, naphthalene-2- sulfonic acid, naphthalene- 1 ,5-disulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate, N-cyclohexylsulfamic acid (with the formation of cyclamates), or with other acid organic compounds, such as ascorbic acid. Pharmaceutically acceptable salts of compounds may also be prepared with a pharmaceutically acceptable cation. Suitable pharmaceutically acceptable cations are well known to those skilled in the art and include alkaline, alkaline earth, ammonium and quaternary ammonium cations. Carbonates or hydrogen carbonates are also possible.

[0038] For oligonucleotides, preferred examples of pharmaceutically acceptable salts include but are not limited to (a) salts formed with cations such as sodium, potassium, ammonium, magnesium, calcium, polyamines such as spermine and spermidine, etc.; (b) acid addition salts formed with inorganic acids, for example hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and the like; (c) salts formed with organic acids such as, for example, acetic acid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaric acid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoic acid, tannic acid, palmitic acid, alginic acid, polyglutamic acid, naphthalenesulfonic acid, methanesulfonic acid, p- toluenesulfonic acid, naphthalenedisulfonic acid, polygalacturonic acid, and the like; and (d) salts formed from elemental anions such as chlorine, bromine, and iodine.

[0039] The antisense compounds of the present invention can be utilized for diagnostics, therapeutics, prophylaxis, and as research reagents and kits. For therapeutics, an animal, preferably a human, suspected of having a disease or disorder, which can be treated by modulating the expression of ACSl , is treated by administering antisense compounds in accordance with this invention. The compounds of the invention can be utilized in pharmaceutical compositions by adding an effective amount of an antisense compound to a suitable pharmaceutically acceptable diluent or carrier. Use of the antisense compounds and methods of the invention may also be useful prophylactically, e.g., to prevent or delay infection, inflammation or tumor formation, for example.

[0040] The antisense compounds of the invention are useful for research and diagnostics, because these compounds hybridize to nucleic acids encoding ACS 1 , enabling sandwich and other assays to easily be constructed to exploit this fact. Hybridization of the antisense oligonucleotides of the invention with a nucleic acid encoding ACSl can be detected by means known in the art. Such means may include conjugation of an enzyme to the oligonucleotide, radiolabelling of the oligonucleotide or any other suitable detection means. Kits using such detection means for detecting the level of ACSl in a sample may also be prepared.

[0041] The present invention also includes pharmaceutical compositions and formulations, which include the antisense compounds of the invention. The pharmaceutical compositions of the present invention may be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (including ophthalmic and to mucous membranes including vaginal and rectal delivery), 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, intraarterial, subcutaneous, intraperitoneal or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Oligonucleotides with at least one 2'-O- methoxyethyl modification are believed to be particularly useful for oral administration. [0042] Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable. Coated condoms, gloves and the like may also be useful. [0043] Compositions and formulations for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets or tablets. Thickeners, flavoring agents, diluents, emulsifiers, dispersing aids or binders may be desirable. [0044] Compositions and formulations for parenteral, intrathecal or intraventricular administration may include sterile aqueous solutions, which may also contain buffers, diluents and other suitable additives such as, but not limited to, penetration enhancers, carrier compounds and other pharmaceutically acceptable carriers or excipients. [0045] Pharmaceutical compositions of the present invention include, but are not limited to, solutions, emulsions, and liposome-containing formulations. These compositions may be generated from a variety of components that include, but are not limited to, preformed liquids, self- emulsifying solids and self-emulsifying semisolids. [0046] The pharmaceutical formulations of the present invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceutical industry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general the formulations are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. [0047] The compositions of the present invention may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances, which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and/or dextran. The suspension may also contain stabilizers.

[0048] In one embodiment of the present invention the pharmaceutical compositions may be formulated and used as foams. Pharmaceutical foams include formulations such as, but not limited to, emulsions, microemulsions, creams, jellies and liposomes. While basically similar in nature these formulations vary in the components and the consistency of the final product. The preparation of such compositions and formulations is generally known to those skilled in the pharmaceutical and formulation arts and may be applied to the formulation of the compositions of the present invention. Emulsions [0049] The compositions of the present invention may be prepared and formulated as emulsions. Emulsions are typically heterogenous systems of one liquid dispersed in another in the form of droplets usually exceeding 0.1 μm in diameter. (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199; Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., Volume 1 , p. 245; Block in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 2, p. 335; Higuchi et al., in Remington 's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 1985, p. 301). Emulsions are often biphasic systems comprising of two immiscible liquid phases intimately mixed and dispersed with each other. In general, emulsions may be either water-in-oil (w/o) or of the oil-in-water (o/w) variety. When an aqueous phase is finely divided into and dispersed as minute droplets into a bulk oily phase the resulting composition is called a water-in-oil (w/o) emulsion. Alternatively, when an oily phase is finely divided into and dispersed as minute droplets into a bulk aqueous phase the resulting composition is called an oil-in-water (o/w) emulsion. Emulsions may contain additional components in addition to the dispersed phases and the active drug, which may be present as a solution in either the aqueous phase, oily phase or itself as a separate phase. Pharmaceutical excipients such as emulsifiers, stabilizers, dyes, and anti-oxidants may also be present in emulsions as needed. Pharmaceutical emulsions may also be multiple emulsions that are comprised of more than two phases such as, for example, in the case of oil- in-water-in-oil (o/w/o) and water-in-oil-in-water (w/o/w) emulsions. Such complex formulations often provide certain advantages that simple binary emulsions do not. Multiple emulsions in which individual oil droplets of an o/w emulsion enclose small water droplets constitute a w/o/w emulsion. Likewise a system of oil droplets enclosed in globules of water stabilized in an oily continuous provides an o/w/o emulsion.

[0050] Emulsions are characterized by little or no thermodynamic stability. Often, the dispersed or discontinuous phase of the emulsion is well dispersed into the external or continuous phase and maintained in this form through the means of emulsifiers or the viscosity of the formulation. Either of the phases of the emulsion may be a semisolid or a solid, as is the case of emulsion-style ointment bases and creams. Other means of stabilizing emulsions entail the use of emulsifiers that may be incorporated into either phase of the emulsion. Emulsifiers may broadly be classified into four categories: synthetic surfactants, naturally occurring emulsifiers, absorption bases, and finely dispersed solids (Idson, in Pharmaceutical Dosaqe Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199).

[0051] Synthetic surfactants, also known as surface active agents, have found wide applicability in the formulation of emulsions and have been reviewed in the literature (Rieger, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), Marcel Dekker, Inc., New York, N.Y., 1988, volume 1, p. 199). Surfactants are typically amphiphilic and comprise a hydrophilic and a hydrophobic portion. The ratio of the hydrophilic to the hydrophobic nature of the surfactant has been termed the hydrophile/lipophile balance (HLB) and is a valuable tool in categorizing and selecting surfactants in the preparation of formulations. Surfactants may be classified into different classes based on the nature of the hydrophilic group: nonionic, anionic, cationic and amphoteric (Rieger, in

Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 285). [0052] Naturally occurring emulsifiers used in emulsion formulations include lanolin, beeswax, phosphatides, lecithin and acacia. Absorption bases possess hydrophilic properties such that they can soak up water to form w/o emulsions yet retain their semisolid consistencies, such as anhydrous lanolin and hydrophilic petrolatum. Finely divided solids have also been used as good emulsifiers especially in combination with surfactants and in viscous preparations. These include polar inorganic solids, such as heavy metal hydroxides, nonswelling clays such as bentonite, attapulgite, hectorite, kaolin, montmorillonite, colloidal aluminum silicate and colloidal magnesium aluminum silicate, pigments and nonpolar solids such as carbon or glyceryl tristearate. [0053] A large variety of non-emulsifying materials are also included in emulsion formulations and contribute to the properties of emulsions. These include fats, oils, waxes, fatty acids, fatty alcohols, fatty esters, humectants, hydrophilic colloids, preservatives, and antioxidants (Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 335; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 199). [0054] Hydrophilic colloids or hydrocolloids include naturally occurring gums and synthetic polymers such as polysaccharides (for example, acacia, agar, alginic acid, carrageenan, guar gum, karaya gum, and tragacanth), cellulose derivatives (for example, carboxymethylcellulose and carboxypropylcellulose), and synthetic polymers (for example, carbomers, cellulose ethers, and carboxyvinyl polymers). These disperse or swell in water to form colloidal solutions that stabilize emulsions by forming strong interfacial films around the dispersed phase droplets and by increasing the viscosity of the external phase. [0055] Since emulsions often contain a number of ingredients such as carbohydrates, proteins, sterols and phosphatides that may readily support the growth of microbes, these formulations often incorporate preservatives. Commonly used preservatives included in emulsion formulations include methyl paraben, propyl paraben, quaternary ammonium salts, benzalkonium chloride, esters of p-hydroxybenzoic acid, and boric acid. Antioxidants are also commonly added to emulsion formulations to prevent deterioration of the formulation. Antioxidants used may be free radical scavengers such as tocopherols, alkyl gallates, butylated hydroxyanisole, butylated hydroxytoluene, or reducing agents such as ascorbic acid and sodium metabisulfite, and antioxidant synergists such as citric acid, tartaric acid, and lecithin.

[0056] The application of emulsion formulations via dermatological, oral, and parenteral routes and methods for their manufacture have been reviewed in the literature (Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 199). Emulsion formulations for oral delivery have been very widely used because of reasons of ease of formulation, efficacy from an absorption and bioavailability standpoint. (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245; Idson, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 199). Mineral-oil base laxatives, oil-soluble vitamins and high fat nutritive preparations are among the materials that have commonly been administered orally as o/w emulsions.

[0057] In one embodiment of the present invention, the compositions of oligonucleotides and nucleic acids are formulated as microemulsions. A microemulsion may be defined as a system of water, oil and amphiphile, which is a single optically isotropic, and thermodynamically stable liquid solution (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1, p. 245). Typically microemulsions are systems that are prepared by first dispersing an oil in an aqueous surfactant solution and then adding a sufficient amount of a fourth component, generally an intermediate chain- length alcohol to form a transparent system. Therefore, microemulsions have also been described as thermodynamically stable, isotropically clear dispersions of two immiscible liquids that are stabilized by interfacial films of surface-active molecules (Leung and Shah, in: Controlled Release of Drugs: Polymers and Aggregate Systems, Rosoff, M., Ed., 1989, VCH Publishers, New York, pages 1852-5). Microemulsions commonly are prepared via a combination of three to five components that include oil, water, surfactant, cosurfactant and electrolyte. Whether the microemulsion is of the water-in-oil (w/o) or an oil-in-water (o/w) type is dependent on the properties of the oil and surfactant used and on the structure and geometric packing of the polar heads and hydrocarbon tails of the surfactant molecules (Schott, in Remington 's Pharmaceutical Sciences, Mack Publishing Co., Easton, PA, 1985, p. 271). [0058] The phenomenological approach utilizing phase diagrams has been extensively studied and has yielded a comprehensive knowledge, to one skilled in the art, of how to formulate microemulsions (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 245; Block, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , p. 335). Compared to conventional emulsions, microemulsions offer the advantage of solubilizing water-insoluble drugs in a formulation of thermodynamically stable droplets that are formed spontaneously.

[0059] Surfactants used in the preparation of microemulsions include, but are not limited to, ionic surfactants, non-ionic surfactants, Brij 96, polyoxyethylene oleyl ethers, polyglycerol fatty acid esters, tetraglycerol monolaurate (ML310), tetraglycerol monooleate (MO310), hexaglycerol monooleate (PO310), hexaglycerol pentaoleate (PO500), decaglycerol monocaprate (MCA750), decaglycerol monooleate (MO750), decaglycerol sequioleate (S0750), decaglycerol decaoleate (DAO750), alone or in combination with cosurfactants. The cosurfactant, usually a short-chain alcohol such as ethanol, 1 -propanol, and 1 -butanol, serves to increase the interfacial fluidity by penetrating into the surfactant film and consequently creating a disordered film because of the void space generated among surfactant molecules. Microemulsions may, however, be prepared without the use of cosurfactants and alcohol-free self-emulsifying microemulsion systems are known in the art. The aqueous phase may typically be, but is not limited to, water, an aqueous solution of the drug, glycerol, PEG300, PEG400, polyglycerols, propylene glycols, and derivatives of ethylene glycol. The oil phase may include, but is not limited to, materials such as Captex 300, Captex 355, Capmul MCM, fatty acid esters, medium chain (C8-C12) mono, di, and triglycerides, polyoxyethylated glyceryl fatty acid esters, fatty alcohols, polyglycolized glycerides, saturated polyglycolized C8-C10 glycerides, vegetable oils and silicone oil. [0060] Microemulsions are particularly of interest from the standpoint of drug solubilization and the enhanced absorption of drugs. Lipid based microemulsions (both o/w and w/o) have been proposed to enhance the oral bioavailability of drugs, including peptides (Constantinides et al.,

Pharmaceutical Research, 1994, 1 1, 1385-1390; Ritschel, Meth. Find. Exp. Clin. Pharmacol., 1993, 13, 205). Microemulsions afford advantages of improved drug solubilization, protection of drug from enzymatic hydrolysis, possible enhancement of drug absorption due to surfactant-induced alterations in membrane fluidity and permeability, ease of preparation, ease of oral administration over solid dosage forms, improved clinical potency, and decreased toxicity (Constantinides et al., Pharmaceutical Research, 1994, 11 , 1385; Ho et al., J. Pharm. Sci., 1996, 85, 138-143). Often microemulsions may form spontaneously when their components are brought together at ambient temperature. This may be particularly advantageous when formulating thermolabile drugs, peptides or oligonucleotides. Microemulsions have also been effective in the transdermal delivery of active components in both cosmetic and pharmaceutical applications. It is expected that the microemulsion compositions and formulations of the present invention will facilitate the increased systemic absorption of oligonucleotides and nucleic acids from the gastrointestinal tract, as well as improve the local cellular uptake of oligonucleotides and nucleic acids within the gastrointestinal tract, vagina, buccal cavity and other areas of administration. [0061] Microemulsions of the present invention may also contain additional components and additives such as sorbitan monostearate (Grill 3), Labrasol, and penetration enhancers to improve the properties of the formulation and to enhance the absorption of the oligonucleotides and nucleic acids of the present invention. Penetration enhancers used in the microemulsions of the present invention may be classified as belonging to one of five broad categories - surfactants, fatty acids, bile salts, chelating agents, and non-chelating non-surfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991 , p. 92). Each of these classes has been discussed above.

[0062] Liposomes

[0063] There are many organized surfactant structures besides microemulsions that have been studied and used for the formulation of drugs. These include monolayers, micelles, bilayers and vesicles. Vesicles, such as liposomes, have attracted great interest because of their specificity and the duration of action they offer from the standpoint of drug delivery. As used in the present invention, the term "Iiposome" means a vesicle composed of amphiphilic lipids arranged in a spherical bilayer or bilayers. [0064] Liposomes are unilamellar or multilamellar vesicles which have a membrane formed from a lipophilic material and an aqueous interior. The aqueous portion contains the composition to be delivered. Cationic liposomes possess the advantage of being able to fuse to the cell wall. Noncationic liposomes, although not able to fuse as efficiently with the cell wall, are taken up by macrophages in vivo. [0065] In order to cross intact mammalian skin, lipid vesicles must pass through a series of fine pores, each with a diameter less than 50 nm, under the influence of a suitable transdermal gradient. Therefore, it is desirable to use a Iiposome, which is highly deformable and able to pass through such fine pores. [0066] Further advantages of liposomes include; liposomes obtained from natural phospholipids are biocompatible and biodegradable; liposomes can incorporate a wide range of water and lipid soluble drugs; liposomes can protect encapsulated drugs in their internal compartments from metabolism and degradation (Rosoff, in Pharmaceutical Dosage Forms, Lieberman, Rieger and Banker (Eds.), 1988, Marcel Dekker, Inc., New York, N.Y., volume 1 , P. 245). Important considerations in the preparation of Iiposome formulations are the lipid surface charge, vesicle size and the aqueous volume of the liposomes. [0067] Liposomes are useful for the transfer and delivery of active ingredients to the site of action. Because the liposomal membrane is structurally similar to biological membranes, when liposomes are applied to a tissue, the liposomes start to merge with the cellular membranes. As the merging of the Iiposome and cell progresses, the liposomal contents are emptied into the cell where the active agent may act. [0068] Liposomal formulations have been the focus of extensive investigation as the mode of delivery for many drugs. There is growing evidence that for topical administration, liposomes present several advantages over other formulations. Such advantages include reduced side- effects related to high systemic absorption of the administered drug, increased accumulation of the administered drug at the desired target, and the ability to administer a wide variety of drugs, both hydrophilic and hydrophobic, into the skin. [0069] Several reports have detailed the ability of liposomes to deliver agents including high-molecular weight DNA into the skin. Compounds including analgesics, antibodies, hormones and high-molecular weight DNAs have been administered to the skin. The majority of applications resulted in the targeting of the upper epidermis. [0070] Liposomes fall into two broad classes. Cationic liposomes are positively charged liposomes, which interact with the negatively charged DNA molecules to form a stable complex. The positively charged DNA/liposome complex binds to the negatively charged cell surface and is internalized in an endosome. Due to the acidic pH within the endosome, the liposomes are ruptured, releasing their contents into the cell cytoplasm (Wang et al., Biochem. Biophys. Res. Commun., 1987, 147, 980 - 985)

[0071] Liposomes, which are pH-sensitive or negatively charged, entrap DNA rather than complex with it. Since both the DNA and the lipid are similarly charged, repulsion rather than complex formation occurs. Nevertheless, some DNA is entrapped within the aqueous interior of these liposomes. pH-sensitive liposomes have been used to deliver DNA encoding the thymidine kinase gene to cell monolayers in culture. Expression of the exogenous gene was detected in the target cells (Zhou et al., Journal of Controlled Release, 1992, 19, 269-274).

[0072] One major type of liposomal composition includes phospholipids other than naturally derived phosphatidylcholine. Neutral Iiposome compositions, for example, can be formed from dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC). Anionic Iiposome compositions generally are formed from dimyristoyl phosphatidylglycerol, while anionic fusogenic liposomes are formed primarily from dioleoyl phosphatidylethanolamine (DOPE). Another type of liposomal composition is formed from phosphatidylcholine (PC) such as, for example, soybean PC, and egg PC. Another type is formed from mixtures of phospholipid and/or phosphatidylcholine and/or cholesterol. [0073] Several studies have assessed the topical delivery of liposomal drug formulations to the skin. Application of liposomes containing interferon to guinea pig skin resulted in a reduction of skin herpes sores while delivery of interferon via other means (e.g. as a solution or as an emulsion) was ineffective (Weiner et al., Journal of Drug Targeting, 1992, 2, 405-410). Further, an additional study tested the efficacy of interferon administered as part of a liposomal formulation to the administration of interferon using an aqueous system, and concluded that the liposomal formulation was superior to aqueous administration (du Plessis et al., Antiviral Research, 1992, 18, 259-265). [0074] Non-ionic liposomal systems have also been examined to determine their utility in the delivery of drugs to the skin, in particular systems comprising non-ionic surfactant and cholesterol. Non-ionic liposomal formulations comprising Novasome ™ I (glyceryl dilaurate/cholesterol/polyoxyethylene-10-stearyl ether) and Novasome™ II (glyceryl distearate/ cholesterol/polyoxyethylene-10-stearyl ether) were used to deliver cyclosporin-A into the dermis of mouse skin. Results indicated that such non-ionic liposomal systems were effective in facilitating the deposition of cyclosporin-A into different layers of the skin (Hu et al. S.TP.Pharma. Sci., 1994, 4, 6, 466). [0075] Liposomes also include "sterically stabilized" liposomes, a term which, as used herein, refers to liposomes comprising one or more specialized lipids that, when incorporated into liposomes, result in enhanced circulation lifetimes relative to liposomes lacking such specialized lipids. Examples of sterically stabilized liposomes are those in which part of the vesicle-forming lipid portion of the Iiposome (A) comprises one or more glycolipids, such as monosialoganglioside G_M ι , or (B) is derivatized with one or more hydrophilic polymers, such as a polyethylene glycol (PEG) moiety. While not wishing to be bound by any particular theory, it is thought in the art that, at least for sterically stabilized liposomes containing gangliosides, sphingomyelin, or PEG-derivatized lipids, the enhanced circulation half-life of these sterically stabilized liposomes derives from a reduced uptake into cells of the reticuloendothelial system (RES) (Allen et al., FEBS Letters, 1987, 223, 42; Wu et al., Cancer Research, 1993, 53, 3765). [0076] Various liposomes comprising one or more glycolipids are known in the art. Papahadjopoulos et al. (Ann. N.Y. Acad. Sci., 1987, 507, 64) reported the ability of monosialoganglioside G_M], galactocerebroside sulfate and phosphatidylinositol to improve blood half-lives of liposomes. These findings were expounded upon by Gabizon et al. (Proc. Natl. Acad. Sci. U.S.A., 1988, 85, 6949). U.S. Patent No. 4,837,028 and WO 88/04924, both to Allen et al., disclose liposomes comprising (1 ) sphingomyelin and (2) the ganglioside Gjor a galactocerebroside sulfate ester. U.S. Patent No. 5,543,152 (Webb et al.) discloses liposomes comprising sphingomyelin. Liposomes comprising 1,2-sn-dimyristoylphosphatidylcholine are disclosed in WO 97/13499 (Lim et al.). [0077] Many liposomes comprising lipids derivatized with one or more hydrophilic polymers, and methods of preparation thereof, are known in the art. Sunamoto et al. (Bull. Chem. Soc. Jpn., 1980, 53, 2778) described liposomes comprising a nonionic detergent, 2C₁₂15G, that contains a PEG moiety. Ilium et al. {FEBS Lett., 1984, 167, 79) noted that hydrophilic coating of polystyrene particles with polymeric glycols results in significantly enhanced blood half-lives. Synthetic phospholipids modified by the attachment of carboxylic groups of polyalkylene glycols (e.g., PEG) are described by Sears (U.S. Patent Nos. 4,426,330 and 4,534,899). Klibanov et al. (FEBS Lett., 1990, 268, 235) described experiments demonstrating that liposomes comprising phosphatidylethanolamine (PE) derivatized with PEG or PEG stearate have significant increases in blood circulation half-lives. Blume et al. (Biochimica et Biophysica Acta, 1990, 1029, 91) extended such observations to other PEG derivatized phospholipids, e.g., DSPE-PEG, formed from the combination of distearoylphosphatidylethanolamine (DSPE) and PEG. Liposomes having covalentiy bound PEG moieties on their external surface are described in European Patent No. EP 0 445 131 Bl and WO 90/04384 to Fisher. Liposome compositions containing 1-20 mole percent of PE derivatized with PEG, and methods of use thereof, are described by Woodle et al. (U.S. Patent Nos. 5,013,556 and 5,356,633) and Martin et al. (U.S. Patent No. 5,213,804 and European Patent No. EP 0 496 813 Bl). Liposomes comprising a number of other lipid-polymer conjugates are disclosed in WO 91/05545 and U.S. Patent No. 5,225,212 (both to Martin et al.) and in WO 94/20073 (Zalipsky et al.) Liposomes comprising PEG-modified ceramide lipids are described in WO 96/10391 (Choi et al.). U.S. Patent Nos.

5,540,935 (Miyazaki et al.) and 5,556,948 (Tagawa et al.) describe PEG- containing liposomes that can be further derivatized with functional moieties on their surfaces. [0078] A limited number of liposomes comprising nucleic acids are known in the art. WO 96/40062 to Thierry et al. discloses methods for encapsulating high molecular weight nucleic acids in liposomes. U.S. Patent No. 5,264,221 to Tagawa et al. discloses protein-bonded liposomes and asserts that the contents of such liposomes may include an antisense RNA. U.S. Patent No. 5,665,710 to Rahman et al. describes certain methods of encapsulating oligodeoxynucleotides in liposomes. WO 97/04787 to Love et al. discloses liposomes comprising antisense oligonucleotides targeted to the raf gene.

[0079] Transfersomes are yet another type of liposomes, and are highly deformable lipid aggregates which are attractive candidates for drug delivery vehicles. Transfersomes may be described as lipid droplets, which are so highly deformable that they are easily able to penetrate through pores, which are smaller than the droplet. Transfersomes are adaptable to the environment in which they are used, e.g. they are self-optimizing (adaptive to the shape of pores in the skin), self-repairing, frequently reach their targets without fragmenting, and often self-loading. To make transfersomes it is possible to add surface edge-activators, usually surfactants, to a standard liposomal composition. Transfersomes have been used to deliver serum albumin to the skin. The transfersome-mediated delivery of serum albumin has been shown to be as effective as subcutaneous injection of a solution containing serum albumin.

[0080] Surfactants find wide application in formulations such as emulsions (including microemulsions) and liposomes. The most common way of classifying and ranking the properties of the many different types of surfactants, both natural and synthetic, is by the use of the hydrophile/lipophile balance (HLB). The nature of the hydrophilic group (also known as the "head") provides the most useful means for categorizing the different surfactants used in formulations (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, NY, 1988, p. 285) [0081] If the surfactant molecule is not ionized, it is classified as a nonionic surfactant. Nonionic surfactants find wide application in pharmaceutical and cosmetic products and are usable over a wide range of pH values. In general their HLB values range from 2 to about 18 depending on their structure. Nonionic surfactants include nonionic esters such as ethylene glycol esters, propylene glycol esters, glyceryl esters, polyglyceryl esters, sorbitan esters, sucrose esters, and ethoxylated esters. Nonionic alkanolamides and ethers such as fatty alcohol ethoxylates, propoxylated alcohols, and ethoxylated/propoxylated block polymers are also included in this class. The polyoxyethylene surfactants are the most popular members of the nonionic surfactant class. [0082] If the surfactant molecule carries a negative charge when it is dissolved or dispersed in water, the surfactant is classified as anionic. Anionic surfactants include carboxylates such as soaps, acyl lactylates, acyl amides of amino acids, esters of sulfuric acid such as alkyl sulfates and ethoxylated alkyl sulfates, sulfonates such as alkyl benzene sulfonates, acyl isethionates, acyl taurates and sulfosuccinates, and phosphates. The most important members of the anionic surfactant class are the alkyl sulfates and the soaps.

[0083] If the surfactant molecule carries a positive charge when it is dissolved or dispersed in water, the surfactant is classified as cationic. Cationic surfactants include quaternary ammonium salts and ethoxylated amines. The quaternary ammonium salts are the most used members of this class.

[0084] If the surfactant molecule has the ability to carry either a positive or negative charge, the surfactant is classified as amphoteric. Amphoteric surfactants include acrylic acid derivatives, substituted alkylamides, N- alkylbetaines and phosphatides.

[0085] The use of surfactants in drug products, formulations and in emulsions has been reviewed (Rieger, in Pharmaceutical Dosage Forms, Marcel Dekker, Inc., New York, NY, 1988, p. 285). Penetration Enhancers [0086] In one embodiment, the present invention employs various penetration enhancers to effect the efficient delivery of nucleic acids particularly oligonucleotides, to the skin of animals. Most drugs are present in solution in both ionized and nonionized forms. However, usually only lipid soluble or lipophilic drugs readily cross cell membranes. It has been discovered that even non-lipophilic drugs may cross cell membranes if the membrane to be crossed is treated with a penetration enhancer. In addition to aiding the diffusion of non-lipophilic drugs across cell membranes, penetration enhancers also enhance the permeability of lipophilic drugs. [0087] Penetration enhancers may be classified as belonging to one of five broad categories, i.e., surfactants, fatty acids, bile salts, chelating agents, and non-chelating nonsurfactants (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92). Each of the above mentioned classes of penetration enhancers are described below in greater detail.

[0088] Surfactants: In connection with the present invention, surfactants (or "surface-active agents") are chemical entities which, when dissolved in an aqueous solution, reduce the surface tension of the solution or the interfacial tension between the aqueous solution and another liquid, with the result that absoφtion of oligonucleotides through the mucosa is enhanced. In addition to bile salts and fatty acids, these penetration enhancers include, for example, sodium lauryl sulfate, polyoxyethylene-9-lauryl ether and polyoxyethylene-20-cetyl ether) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92); and perfluorochemical emulsions, such as FC-43. Takahashi et al., J. Pharm. Pharmacol., 1988, 40, 252). [0089] Fatty acids: Various fatty acids and their derivatives which act as penetration enhancers include, for example, oleic acid, lauric acid, capric acid (n-decanoic acid), myristic acid, palmitic acid, stearic acid, linoleic acid, linolenic acid, dicaprate, tricaprate, monoolein (l-monooleoyl-.rac- glycerol), dilaurin, caprylic acid, arachidonic acid, glycerol 1 -monocaprate, l-dodecylazacycloheptan-2-one, acylcarnitines, acylcholines, C,.^ alkyl esters thereof (e.g., methyl, isopropyl and t-butyl), and mono- and di- glycerides thereof (i.e., oleate, laurate, caprate, myristate, palmitate, stearate, linoleate, etc.) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, p.92; Muranishi, Critical Reviews in Therapeutic

Drug Carrier Systems, 1990, 7, 1-33; El Hariri et al., J. Pharm. Pharmacol.,

1992, 44, 651-654).

|0090] Bile salts: The physiological role of bile includes the facilitation of dispersion and absoφtion of lipids and fat-soluble vitamins (Brunton, Chapter 38 in: Goodman & Gilman's The Pharmacological Basis of

Therapeutics, 9th Ed., Hardman et al. Eds. McGraw-Hill, New York, 1996, pp. 934-935). Various natural bile salts, and their synthetic derivatives, act as penetration enhancers. Thus the term "bile salts" includes any of the naturally occurring components of bile as well as any of their synthetic derivatives. The bile salts of the invention include, for example, cholic acid (or its pharmaceutically acceptable sodium salt, sodium cholate), dehydrocholic acid (sodium dehydrocholate), deoxycholic acid (sodium deoxycholate), glucholic acid (sodium glucholate), glycholic acid (sodium glycocholate), glycodeoxycholic acid (sodium glycodeoxycholate), taurocholic acid (sodium taurocholate), taurodeoxycholic acid (sodium taurodeoxycholate), chenodeoxycholic acid (sodium chenodeoxycholate), ursodeoxycholic acid (UDCA), sodium tauro-24,25-dihydro-fusidate (STDHF), sodium glycodihydrofusidate'and polyoxyethylene-9-lauryl ether (POE) (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991 , page 92; Swinyard, Chapter 39 In: Remington 's Pharmaceutical Sciences, 18th Ed., Gennaro, ed., Mack Publishing Co., Easton, PA, 1990, pages 782-783; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Yamamoto et al., J. Pharm. Exp. Ther., 1992, 263, 25; Yamashita et al., J. Pharm. Sci., 1990, 79, 579-583). [0091] Chelating Agents: Chelating agents, as used in connection with the present invention, can be defined as compounds that remove metallic ions from solution by forming complexes therewith, with the result that absorption of oligonucleotides through the mucosa is enhanced. With regards to their use as penetration enhancers in the present invention, chelating agents have the added advantage of also serving as DNase inhibitors, as most characterized DNA nucleases require a divalent metal ion for catalysis and are thus inhibited by chelating agents (Jarrett, J. Chromatogr., 1993, 618, 315-339). Chelating agents of the invention include but are not limited to disodium. ethylenediaminetetraacetate (EDTA), citric acid, salicylates (e.g., sodium salicylate, 5-methoxysalicylate and homovanilate), N-acyl derivatives of collagen, laureth-9 and N-amino acyl derivatives of beta-diketones (enamines)(Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991 , page 92; Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33; Buur et al., J. Control Rel., 1990, 14, 43-51). [0092] Non-chelating non-surfactants: As used herein, nonchelating non-surfactant penetration enhancing compounds can be defined as compounds that demonstrate insignificant activity as chelating agents or as surfactants but that nonetheless enhance absoφtion of oligonucleotides through the alimentary mucosa (Muranishi, Critical Reviews in Therapeutic Drug Carrier Systems, 1990, 7, 1-33). This class of penetration enhancers include, for example, unsaturated cyclic ureas, 1 -alkyl- and 1- alkenylazacyclo-alkanone derivatives (Lee et al., Critical Reviews in Therapeutic Drug Carrier Systems, 1991, page 92); and non-steroidal anti- inflammatory agents such as diclofenac sodium, indomethacin and phenylbutazone (Yamashita et al., J. Pharm. Pharmacol., 1987, 39, 621-

626).

[0093] Agents that enhance uptake of oligonucleotides at the cellular level may also be added to the pharmaceutical and other compositions of the present invention. For example, cationic lipids, such as lipofectin (Junichi et al, U.S. Patent No. 5,705,188), cationic glycerol derivatives, and polycationic molecules, such as polylysine (Lollo et al., PCT Application WO 97/30731), are also known to enhance the cellular uptake of oligonucleotides. [0094] Other agents may be utilized to enhance the penetration of the administered nucleic acids, including glycols such as ethylene glycol and propylene glycol, pyrrols such as 2-pyrrol, azones, and teφenes such as limonene and menthone.

Carriers [0095] Certain compositions of the present invention also incoφorate carrier compounds in the formulation. As used herein, "carrier compound" or "carrier" can refer to a nucleic acid, or analog thereof, which is inert (i.e., does not possess biological activity per se) but is recognized as a nucleic acid by in vivo processes that reduce the bioavailability of a nucleic acid having biological activity by, for example, degrading the biologically active nucleic acid or promoting its removal from circulation. The coadministration of a nucleic acid and a carrier compound, typically with an excess of the latter substance, can result in a substantial reduction of the amount of nucleic acid recovered in the liver, kidney or other extracirculatory reservoirs, presumably due to competition between the carrier compound and the nucleic acid for a common receptor. For example, the recovery of a partially phosphorothioate oligonucleotide in hepatic tissue can be reduced when it is coadministered with polyinosinic acid, dextran sulfate, polycytidic acid or 4-acetamido-4'isothiocyano-stilbene-

2,2'disulfonic acid (Miyao et al., Antisense Res. Dev., 1995, 5, 115-121; Takakura et al., Antisense & Nucl. Acid Drug Dev., 1996, 6, 177-183).

Excipients [0096] In contrast to a carrier compound, a "pharmaceutical carrier" or "excipient" is a pharmaceutically acceptable solvent, suspending agent or any other pharmacologically inert vehicle for delivering one or more nucleic acids to an animal. The excipient may be liquid or solid and is selected, with the planned manner of administration in mind, so as to provide for the desired bulk, consistency, etc., when combined with a nucleic acid and the other components of a given pharmaceutical composition. Typical pharmaceutical carriers include, but are not limited to, binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose, etc.); fillers (e.g., lactose and other sugars, microcrystalline cellulose, pectin, gelatin, calcium sulfate, ethyl cellulose, polyacrylates or calcium hydrogen phosphate, etc.); lubricants (e.g., magnesium stearate, talc, silica, colloidal silicon dioxide, stearic acid, metallic stearates, hydrogenated vegetable oils, corn starch, polyethylene glycols, sodium benzoate, sodium acetate, etc.); disintegrants (e.g., starch, sodium starch glycolate, etc.); and wetting agents (e.g., sodium lauryl sulphate, etc.). [0097] Pharmaceutically acceptable organic or inorganic excipient suitable for non-parenteral administration, which does not deleteriously react with nucleic acids, can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like. [0098] Formulations for topical administration of nucleic acids may include sterile and non-sterile aqueous solutions, non-aqueous solutions in common solvents such as alcohols, or solutions of the nucleic acids in liquid or solid oil bases. The solutions may also contain buffers, diluents and other suitable additives. Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration, which do not deleteriously react with nucleic acids, can be used. [0099] Suitable pharmaceutically acceptable excipients include, but are not limited to, water, salt solutions, alcohol, polyethylene glycols, gelatin, lactose, amylose, magnesium stearate, talc, silicic acid, viscous paraffin, hydroxymethylcellulose, polyvinylpyrrolidone and the like.

Other Components

[00100] The compositions of the present invention may additionally contain other adjunct components conventionally found in pharmaceutical compositions, at their art-established usage levels. Thus, for example, the compositions may contain additional, compatible, pharmaceutically-active materials such as, for example, antipruritics, astringents, local anesthetics or anti-inflammatory agents, or may contain additional materials useful in physically formulating various dosage forms of the compositions of the present invention, such as dyes, flavoring agents, preservatives, antioxidants, opacifiers, thickening agents and stabilizers. However, such materials, when added, should not unduly interfere with the biological activities of the components of the compositions of the present invention.' The formulations can be sterilized and, if desired, mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, colorings, flavorings and/or aromatic substances and the like which do not deleteriously interact with the nucleic acid(s) of the formulation. [00101] Aqueous suspensions may contain substances that increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol, and/or dextran. The suspension may also contain stabilizers.

[00102] Certain embodiments of the invention provide pharmaceutical compositions containing (a) one or more antisense compounds and (b) one or more other chemotherapeutic agents which function by a non-antisense mechanism. Examples of such chemotherapeutic agents include, but are not limited to, anticancer drugs such as daunorubicin, dactinomycin, doxorubicin, bleomycin, mitomycin, nitrogen mustard, chlorambucil, melphalan, cyclophosphamide, 6-mercaptopurine, 6-thioguanine, cytarabine (CA), 5-fluorouracil (5-FU), floxuridine (5-FUdR), methotrexate (MTX), colchicine, vincristine, vinblastine, etoposide, teniposide, cisplatin and diethylstilbestrol (DES). See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 1206- 1228). Anti-inflammatory drugs, including but not limited to nonsteroidal anti-inflammatory drugs and corticosteroids, and antiviral drugs, including but not limited to ribivirin, vidarabine, acyclovir and ganciclovir, may also be combined in compositions of the invention. See, generally, The Merck Manual of Diagnosis and Therapy, 15th Ed., Berkow et al., eds., 1987, Rahway, N.J., pages 2499-2506 and 46-49, respectively). Other non- antisense chemotherapeutic agents are also within the scope of this invention. Two or more combined compounds may be used together or sequentially.

[00103] In another related embodiment, compositions of the invention may contain one or more antisense compounds, particularly oligonucleotides, targeted to a first nucleic acid and one or more additional antisense compounds targeted to a second nucleic acid target. Numerous examples of antisense compounds are known in the art. Two or more combined compounds may be used together or sequentially. [00104] The formulation of therapeutic compositions and their subsequent administration is believed to be within the skill of those in the art. Dosing is dependent on severity and responsiveness of the disease state to be treated, with the course of treatment lasting from several days to several months, or until a cure is effected or a diminution of the disease state is achieved. Optimal dosing schedules can be calculated from measurements of drug accumulation in the body of the patient. Persons of ordinary skill can easily determine optimum dosages, dosing methodologies and repetition rates. Optimum dosages may vary depending on the relative potency of individual oligonucleotides, and can generally be estimated based on EC₅₀S found to be effective in in vitro and in vivo animal models. In general, dosage is from 0.01 μg to 100 g per kg of body weight, and may be given once or more daily, weekly, monthly or yearly, or even once every 2 to 20 years. Persons of ordinary skill in the art can easily estimate repetition rates for dosing based on measured residence times and concentrations of the drug in bodily fluids or tissues. Following successful treatment, it may be desirable to have the patient undergo maintenance therapy to prevent the recurrence of the disease state, wherein the oligonucleotide is administered in maintenance doses, ranging from 0.01 μg to 100 g per kg of body weight, once or more daily, to once every 20 years. [00105] While the present invention has been described with specificity in accordance with certain of its preferred embodiments, the following examples serve only to illustrate the invention and are not intended to limit the same.

EXAMPLES

Example 1

Nucleoside Phosphoramidites for Oligonucleotide Synthesis Deoxy and 2 '-alkoxy amidites

[00106] 2'-Deoxy and 2'-methoxy beta-cyanoethyldiisopropyl phosphoramidites are available from commercial sources (e.g. Chemgenes, Needham MA or Glen Research, Inc. Sterling VA). Other 2'-O-alkoxy substituted nucleoside amidites are prepared as described in U.S. Patent 5,506,351, herein incoφorated by reference. For oligonucleotides synthesized using 2'-alkoxy amidites, the standard cycle for unmodified oligonucleotides is utilized, except the wait step after pulse delivery of tetrazole and base is increased to 360 seconds.

[00107] Oligonucleotides containing 5-methyl-2'-deoxycytidine (5-

Me-C) nucleotides are synthesized according to published methods [Sanghvi, et. al, Nucleic Acids Research, 1993, 21 , 3197-3203] using commercially available phosphoramidites (Glen Research, Sterling VA or ChemGenes, Needham MA). 2'-Fluoro amidites 2'-FIuorodeoxyadenosine amidites

[00108] 2'-fluoro oligonucleotides are synthesized as described previously [Kawasaki, et. al., J. Med. Chem., 1993, 36, 831-841] and United States patent 5,670,633, herein incoφorated by reference. Briefly, the protected nucleoside N6-benzoyl-2'-deoxy-2'-fluoroadenosine is synthesized utilizing commercially available 9-beta-D- arabinofuranosyladenine as starting material and by modifying literature procedures whereby the 2'-alpha-fluoro atom is introduced by a S_N2- displacement of a 2'-beta-trityl group. Thus N6-benzoyl-9-beta-D- arabinofuranosyladenine is selectively protected in moderate yield as the 3',5'-ditetrahydropyranyl (THP) intermediate. Deprotection of the THP and N6-benzoyl groups is accomplished using standard methodologies and standard methods are used to obtain the 5'-dimethoxytrityl-(DMT) and 5'- DMT-3'-phosphoramidite intermediates. 2'-Fluorodeoxyguanosine

[00109] The synthesis of 2'-deoxy-2'-fluoroguanosine is accomplished using tetraisopropyldisiloxanyl (TPDS) protected 9-beta-D- arabinofuranosylguanine as starting material, and conversion to the intermediate diisobutyrylarabinofuranosylguanosine. Deprotection of the TPDS group is followed by protection of the hydroxyl group with THP to give diisobutyryl di-THP protected arabinofuranosylguanine. Selective O- deacylation and triflation is followed by treatment of the crude product with fluoride, then deprotection of the THP groups. Standard methodologies are used to obtain the 5'-DMT- and 5 '-DMT-3 '-phosphoramidites. 2'-Fluorouridine

[00110] Synthesis of 2'-deoxy-2'-fluorouridine is accomplished by the modification of a literature procedure in which 2,2'anhydro-l-beta-D- arabinofuranosyl uracil is treated with 70% hydrogen fluoride-pyridine. Standard procedures are used to obtain the 5'-DMT and 5'-DMT-3'- phosphoramidites. 2'-Fluorodeoxycytidine

[00111] 2'-deoxy-2'-fluorocytidine is synthesized via amination of 2'-deoxy-2'-fluorouridine, followed by selective protection to give N4- benzoyl-2'-deoxy-2'-fluorocytidine. Standard procedures are used to obtain the 5'-DMT and 5 '-DMT-3 'phosphoramidites. 2'-O-(2-Methoxyethyl) modified amidites [00112] 2 '-O-Methoxy ethyl-substituted nucleoside amidites are prepared as follows, or alternatively, as per the methods of Martin, P., Helvetica Chimica Acta, 1995, 78, 486-504. 2,2'-Anhydro[l-(beta-D-arabinofuranosyl)-5-methyluridinel [00113] 5-Methyluridine (ribosylthymine, commercially available through Yamasa, Choshi, Japan) (72.0 g, 0.279 M), diphenylcarbonate (90.0 g, 0.420 M) and sodium bicarbonate (2.0 g, 0.024 M) are added to DMF (300 mL). The mixture is heated to reflux, with stirring, allowing the evolved carbon dioxide gas to be released in a controlled manner. After 1 hour, the slightly darkened solution is concentrated under reduced pressure. The resulting syrup is poured into diethylether (2.5 L), with stirring. The product formed a gum. The ether is decanted and the residue is dissolved in a minimum amount of methanol (ca. 400 mL). The solution is poured into fresh ether (2.5 L) to yield a stiff gum. The ether is decanted and the gum is dried in a vacuum oven (60°C at 1 mm Hg for 24 h) to give a solid that is crushed to a light tan powder. The material is used as is for further reactions (or it can be purified further by column chromatography using a gradient of methanol in ethyl acetate (10-25%) to give a white solid. 2'-O-Methoxyethyl-5-methyluridine

[00114] 2,2'-Anhydro-5-methyluridine (195 g, 0.81 M), tris(2- methoxyethyl)borate (231 g, 0.98 M) and 2-methoxyethanol (1.2 L) are added to a 2 L stainless steel pressure vessel and placed in a pre-heated oil bath at 160°C. After heating for 48 hours at 155-160°C, the vessel is opened and the solution evaporated to dryness and triturated with MeOH (200 mL). The residue is suspended in hot acetone (1 L). The insoluble salts are filtered, washed with acetone (150 mL) and the filtrate evaporated. The residue (280 g) is dissolved in CH₃CN (600 mL) and evaporated. A silica gel column (3 kg) is packed in CH2CI₂ /acetone /MeOH (20:5:3) containing 0.5% Et₃NH. The residue is dissolved in CH₂C1₂ (250 mL) and adsorbed onto silica (150 g) prior to loading onto the column. The product is eluted with the packing solvent to give the title product. Additional material can be obtained by reworking impure fractions. 2'-O-MethoxyethyI-5'-O-dimethoxytrityI-5-methyluridine |00115] 2'-O-Methoxyethyl-5-methyluridine (160 g, 0.506 M) is co- evaporated with pyridine (250 mL) and the dried residue dissolved in pyridine (1.3 L). A first aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) is added and the mixture stirred at room temperature for one hour. A second aliquot of dimethoxytrityl chloride (94.3 g, 0.278 M) is added and the reaction stirred for an additional one hour. Methanol (170 mL) is then added to stop the reaction. The solvent is evaporated and triturated with CH₃CN (200 mL) The residue is dissolved in CHCl (1.5 L) and extracted with 2x500 mL of saturated NaHCO₃ and 2x500 mL of saturated NaCl. The organic phase is dried over Na₂SO , filtered, and evaporated. The residue is purified on a 3.5 kg silica gel column, packed and eluted with EtOAc/hexane/ acetone (5:5:1) containing 0-5% Et NH. The pure fractions are evaporated to give the title product.

3'-O-Acetyl-2'-O-methoxyethyl-5'-O-dirnethoxytrityl-5-methyluridine [00116] 2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine

(106 g, 0.167 M), DMF/pyridine (750 mL of a 3:1 mixture prepared from 562 mL of DMF and 188 mL of pyridine) and acetic anhydride (24.38 mL, 0.258 M) are combined and stirred at room temperature for 24 hours. The reaction is monitored by TLC by first quenching the TLC sample with the addition of MeOH. Upon completion of the reaction, as judged by TLC, MeOH (50 mL) is added and the mixture evaporated at 35°C. The residue is dissolved in CHCl ₃ (800 mL) and extracted with 2x200 mL of saturated sodium bicarbonate and 2x200 mL of saturated NaCl. The water layers are back extracted with 200 mL of CHCl ₃. The combined organics are dried with sodium sulfate and evaporated to a residue. The residue is purified on a 3.5 kg silica gel column and eluted using EtOAc/hexane(4:l). Pure product fractions are evaporated to yield the title compounds. 3'-O-Acetyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5-methyl-4- triazoleuridine

[00117] A first solution is prepared by dissolving 3'-O-acetyl-2'-O- methoxyethyl-5'-O-dimethoxytrityl-5-methyluridine (96 g, 0.144 M) in CH₃CN (700 mL) and set aside. Triethylamine (189 mL, 1.44 M) is added to a solution of triazole (90 g, 1.3 M) in CH₃CN (1 L), cooled to -5°C and stirred for 0.5 h using an overhead stirrer. POCI₃ is added dropwise, over a 30 minute period, to the stirred solution maintained at 0-10°C, and the resulting mixture stirred for an additional 2 hours. The first solution is added dropwise, over a 45 minute period, to the latter solution. The resulting reaction mixture is stored overnight in a cold room. Salts are filtered from the reaction mixture and the solution is evaporated. The residue is dissolved in EtOAc (1 L) and the insoluble solids are removed by filtration. The filtrate is washed with 1x300 mL of NaHCO₃ and 2x300 mL of saturated NaCl, dried over sodium sulfate and evaporated. The residue is triturated with EtOAc to give the title compound.

2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methylcytidine [00118] A solution of 3'-O-acetyl-2'-O-methoxyethyl-5'-O- dimethoxytrityl-5-methyl-4-triazoleuridine (103 g, 0.141 M) in dioxane (500 mL) and NH₄OH (30 mL) is stirred at room temperature for 2 hours. The dioxane solution is evaporated and the residue azeotroped with MeOH (2x200 mL). The residue is dissolved in MeOH (300 mL) and transferred to a 2 liter stainless steel pressure vessel. MeOH (400 mL) saturated with NH₃ gas is added and the vessel heated to 100°C for 2 hours (TLC showed complete conversion). The vessel contents are evaporated to dryness and the residue is dissolved in EtOAc (500 mL) and washed once with saturated NaCl (200 mL). The organics are dried over sodium sulfate and the solvent is evaporated to give the title compound.

N4-Benzoyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5-methylcytidine [00119] 2'-O-Methoxyethyl-5'-O-dimethoxytrityl-5-methylcytidine (85 g, 0.134 M) is dissolved in DMF (800 mL) and benzoic anhydride (37.2 g, 0.165 M) is added with stirring. After stirring for 3 hours, TLC showed the reaction to be approximately 95% complete. The solvent is evaporated and the residue azeotroped with MeOH (200 mL). The residue is dissolved in CHCl ₃ (700 mL) and extracted with saturated NaHCO, (2x300 L) and saturated NaCl (2x300 mL), dried over MgSO and evaporated to give a residue. The residue is chromatographed on a 1.5 kg silica column using EtOAc/hexane (1 :1) containing 0-5% Et NH as the eluting solvent. The pure product fractions are evaporated to give the title compound. N4-Benzoyl-2'-O-methoxyethyl-5'-O-dimethoxytrityl-5-methylcytidine- 3'-amidite

[00120] N4-Benzoyl-2 ' -O-methoxyethyl-5 ' -O-dimethoxytrityl-5 - methylcytidine (74 g, 0.10 M) is dissolved in CH2CI₂ (1 L) Tetrazole diisopropylamine (7.1 g) and 2-cyanoethoxy-tetra(isopropyl)phosphite (40.5 mL, 0.123 M) are added with stirring, under a nitrogen atmosphere. The resulting mixture is stirred for 20 hours at room temperature (TLC showed the reaction to be 95% complete). The reaction mixture is extracted with saturated NaHCO₃ (1x300 mL) and saturated NaCl (3x300 mL). The aqueous washes are back-extracted with CH2CI2 (300 mL), and the extracts are combined, dried over MgSO₄ and concentrated. The residue obtained is chromatographed on a 1.5 kg silica column using EtOAc/hexane (3: 1) as the eluting solvent. The pure fractions were combined to give the title compound.

2'-O-(Aminooxyethyl) nucleoside amidites and 2'-O- (dimethylaminooxyethyl) nucleoside amidites 2'-(Dimethylaminooxyethoxy) nucleoside amidites [00121] 2'-(Dimethylaminooxyethoxy) nucleoside amidites [also known in the art as 2'-O-(dimethylaminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and guanosine nucleoside amidites are prepared similarly to the thymidine (5- methyluridine) except the exocyclic amines are protected with a benzoyl moiety in the case of adenosine and cytidine and with isobutyryl in the case of guanosine.

5'-O-tert-Butyldiphenylsilyl -O² -2'-anhydro-5-methyluridine [00122] O² -2'-anhydro-5-methyluridine (Pro. Bio. Sint., Varese, Italy, lOO.Og, 0.4'6 mmol), dimethylaminopyridine (0.66g, 0.013eq,

0.0054mmol) are dissolved in dry pyridine (500 ml) at ambient temperature under an argon atmosphere and with mechanical stirring, tert- Butyldiphenylchlorosilane (125.8g, 1 19.0mL, l.leq, 0.458mmol) is added in one portion. The reaction is stirred for 16 h at ambient temperature. TLC (Rf 0.22, ethyl acetate) indicated a complete reaction. The solution is concentrated under reduced pressure to a thick oil. This is partitioned between dichloromethane (1 L) and saturated sodium bicarbonate (2x1 L) and brine (1 L). The organic layer is dried over sodium sulfate and concentrated under reduced pressure to a thick oil. The oil is dissolved in a 1 :1 mixture of ethyl acetate and ethyl ether (600mL) and the solution is cooled to -10°C. The resulting crystalline product is collected by filtration, washed with ethyl ether (3x200 mL), and dried (40°C, 1mm Hg, 24 h) to a white solid 5'-O-tert-Butyldiphenylsilyl-2'-O-(2-hydroxyethyl)-5-methyluridine [00123] In a 2 L stainless steel, unstirred pressure reactor is added borane in tetrahydrofuran (1.0 M, 2.0 eq, 622 mL). In the fume hood and with manual stirring, ethylene glycol (350 mL, excess) is added cautiously at first until the evolution of hydrogen gas subsides. 5'-O-tert- Butyldiphenylsilyl-O²-2'anhydro-5-methyluridine (149 g, 0.3'1 mol) and sodium bicarbonate (0.074 g, 0.003 eq) are added with manual stirring. The reactor is sealed and heated in an oil bath until an internal temperature of 160°C is reached and then maintained for 16 h (pressure < 100 psig). The reaction vessel is cooled to ambient and opened. TLC (Rf 0.67 for desired product and Rf 0.82 for ara-T side product, ethyl acetate) indicated about 70% conversion to the product. In order to avoid additional side product formation, the reaction is stopped, concentrated under reduced pressure (10 to 1mm, Hg) in a warm water bath (40-100°C) with the more extreme conditions used to remove the ethylene glycol. [Alternatively, once the low boiling solvent is gone, the remaining solution can be partitioned between ethyl acetate and water. The product will be in the organic phase.] The residue is purified by column chromatography (2kg silica gel, ethyl acetate- hexanes gradient 1 :1 to 4:1). The appropriate fractions are combined, stripped and dried to product as a white crisp foam, contaminated starting material, and pure reusable starting material.

2'-O-([2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5-methyIuridine [00124] 5'-O-tert-Butyldiphenylsilyl-2'-O-(2-hydroxyethyl)-5- methyluridine (20g, 36.98mmol) is mixed with triphenylphosphine (11.63g, 44.36mmol) and N-hydroxyphthalimide (7.24g, 44.36mmol). It is then dried over P₂O₅ under high vacuum for two days at 40°C. The reaction mixture is flushed with argon and dry THF (369.8mL, Aldrich, sure seal bottle) is added to get a clear solution. Diethyl-azodicarboxylate (6.98mL, 44.36mmol) is added dropwise to the reaction mixture. The rate of addition is maintained such that resulting deep red coloration is just discharged before adding the next drop. After the addition is complete, the reaction is stirred for 4 hrs. By that time TLC showed the completion of the reaction (ethylacetate:hexane, 60:40). The solvent is evaporated in vacuum. Residue obtained is placed on a flash column and eluted with ethyl acetate :hexane (60:40), to get 2'-O-([2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5- methyluridine as white foam.

5'-O-tert-butyldiphenylsilyI-2'-O-[(2-formadoximinooxy)ethyl]-5- methyluridine

[00125] 2'-O-([2-phthalimidoxy)ethyl]-5'-t-butyldiphenylsilyl-5- methyluridine (3.1g, 4.5mmol) is dissolved in dry CH₂CI₂ (4.5mL) and methylhydrazine (300mL, 4.64mmol) is added dropwise at -10°C to 0°C. After 1 h the mixture is filtered, the filtrate is washed with ice cold CH2CI2 and the combined organic phase is washed with water, brine and dried over anhydrous Na₂SO₄. The solution is concentrated to get 2'-O(aminooxyethyl) thymidine, which is then dissolved in MeOH (67.5mL). To this formaldehyde (20% aqueous solution, w/w, 1.1 eq.) is added and the resulting mixture is stirred for 1 h. Solvent is removed under vacuum; residue chromatographed to get 5'-O-tert-butyldiphenylsilyl-2'-O-[(2- formadoximinooxy) ethyl]-5-methyluridine as white foam. 5'-O-tert-Butyldiphenylsilyl-2'-O-[N,N-dimethylaminooxyethyl]-5- methyluridine [00126] 5'-O-tert-butyldiphenylsilyl-2'-O-[(2- formadoximinooxy)ethyl]-5-methyluridine (1.77g, 3.12mmol) is dissolved in a solution of 1 M pyridinium p-toluenesulfonate (PPTS) in dry MeOH (30.6mL). Sodium cyanoborohydride (0.39g, 6.13mmol) is added to this solution at 10°C under inert atmosphere. The reaction mixture is stirred for 10 minutes at 10°C. After that the reaction vessel is removed from the ice bath and stirred at room temperature for 2 h, the reaction monitored by TLC (5% MeOH in CH₂C1₂). Aqueous NaHCO solution (5%, lOmL) is added and extracted with ethyl acetate (2x20mL). Ethyl acetate phase is dried over anhydrous Na₂SO , evaporated to dryness. Residue is dissolved in a solution of IM PPTS in MeOH (30.6mL). Formaldehyde (20% w/w, 30mL, 3.37mmol) is added and the reaction mixture is stirred at room temperature for 10 minutes. Reaction mixture cooled to 10°C in an ice bath, sodium cyanoborohydride (0.39g, 6.13mmol) is added, and reaction mixture stirred at 10°C for 10 minutes. After 10 minutes, the reaction mixture is removed from the ice bath and stirred at room temperature for 2 hrs. To the reaction mixture 5% NaHCO₃ (25mL) solution is added and extracted with ethyl acetate (2x25mL). Ethyl acetate layer is dried over anhydrous Na₂SO₄ and evaporated to dryness. The residue obtained is purified by flash column chromatography and eluted with 5% MeOH in CH₂C1₂ to get 5 '-O- tertbutyldiphenylsilyl-2'-O-[N,N-dimethylaminooxyethyl]-5- methyluridine as a white foam.

2'-O-(dimethylaminooxyethyι)-5-methyluridine

[00127] Triethylamine trihydrofluoride (3.91 mL, 24.0mmol) is dissolved in dry THF and triethylamine (1.67mL, 12mmol, dry, kept over KOH). This mixture of triethylamine-2HF is then added to 5'-O-tert- butyldiphenylsilyl-2'-O-[N,N-dimethylaminooxyethyl]-5-methyluridine (1.40g, 2.4mmol) and stirred at room temperature for 24 hrs. Reaction is monitored by TLC (5%> MeOH in CH2CI2). Solvent is removed under vacuum and the residue placed on a flash column and eluted with 10% MeOH in CH₂CI₂ to get 2'-O-(dimethylaminooxyethyl)-5-methyluridine. 5'-O-DMT-2'-O-(dimethylaminooxyethyl)-5-methyluridine [00128] 2'-O-(dimethylaminooxyethyl)-5-methyluridine (750mg,

2.17mmol) is dried over P₂O₅ under high vacuum overnight at 40°C. It is then co-evaporated with anhydrous pyridine (20mL). The residue obtained is dissolved in pyridine (1 lmL) under argon atmosphere. 4- dimethylaminopyridine (26.5mg, 2.60mmol), 4,4 '-dimethoxytrityl chloride (880mg, 2.60mmol) is added to the mixture and the reaction mixture is stirred at room temperature until all of the starting material disappeared. Pyridine is removed under vacuum and the residue chromatographed and eluted with 10% MeOH in CH₂CI₂ (containing a few drops of pyridine) to get 5'-O-DMT-2'-0(dimethylamino-oxyethyl)-5-methyluridine. 5'-O-DMT-2'-O-(2-N,N-dimethylaminooxyethyl)-5-methyluridine-3'- [(2-cyanoethyl)-N,N- diisopropylphosphoramidite] [00129] 5'-O-DMT-2'-O-(dimethylaminooxyethyl)-5-methyluridine

(1.08g, 1.67mmol) is co-evaporated with toluene (20mL). To the residue N,N-diisopropylamine tetrazonide (0.29g, 1.67mmol) is added and dried over P20, under high vacuum overnight at 40°C. Then the reaction mixture is dissolved in anhydrous acetonitrile (8.4mL) and 2-cyanoethyl-N,N,N^l,N¹- tetraisopropylphosphoramidite (2.12mL, 6.08mmol) is added. The reaction mixture is stirred at ambient temperature for 4 hrs under inert atmosphere. The progress of the reaction is monitored by TLC (hexane:ethyl acetate 1 :1). The solvent is evaporated, then the residue is dissolved in ethyl acetate (70mL) and washed with 5% aqueous NaHCO₃ (40mL). Ethyl acetate layer is dried over anhydrous Na₂SO₄ and concentrated. Residue obtained is chromatographed (ethyl acetate as eluent) to get 5'-O-DMT-2'-O-(2-N,N- dimethylaminooxyethyl)-5-methyluridine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramidite] as a foam. 2'-(Aminooxyethoxy) nucleoside amidites [00130] 2'-(Aminooxyethoxy) nucleoside amidites [also known in the art as 2'-O-(aminooxyethyl) nucleoside amidites] are prepared as described in the following paragraphs. Adenosine, cytidine and thymidine nucleoside amidites are prepared similarly. N2-isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5'-O-(4,4'- dimethoxytrityl)guanosine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramidite]

[00131] The 2'-O-aminooxyethyl guanosine analog may be obtained by selective 2'-O-alkylation of diaminopurine riboside. Multigram quantities of diaminopurine riboside may be purchased from Schering AG (Berlin) to provide 2'-O-(2-ethylacetyl) diaminopurine riboside along with a minor amount of the 3'-O-isomer. 2'-O-(2-ethylacetyl) diaminopurine riboside may be resolved and converted to 2'-O-(2ethylacetyl)guanosine by treatment with adenosine deaminase. (McGee, D. P. C, Cook, P. D., Guinosso, C. J., WO 94/02501 Al 940203.) Standard protection procedures should afford 2'-O-(2-ethylacetyl)-5'-O-(4,4'-dimethoxytrityl)guanosine and 2-N-isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5'-O- (4,4'-dimethoxytrityl)guanosine which may be reduced to provide 2-N- isobutyryl-6-O-diphenylcarbamoyl-2'-O-(2-ethylacetyl)-5'-O-(4,4'- dimethoxytrityl)guanosine. As before the hydroxyl group may be displaced by N-hydroxyphthalimide via a Mitsunobu reaction, and the protected nucleoside may phosphitylated as usual to yield 2-N-isobutyryl-6-O- diphenylcarbamoyl-2 ' -O-(2-ethylacetyl)-5 ' -O-(4,4 ' - dimethoxytrityl)guanosine-3'-[(2-cyanoethyl)-N,N- diisopropylphosphoramiditel. 2'-dimethylaminoethoxyethoxy (2'-DMAEOE) nucleoside amidites [00132] 2' -dimethyl aminoethoxyethoxy nucleoside amidites (also known in the art as 2'-O-dimethylaminoethoxyethyl, i.e., 2O-CH₂-O-CH - N(CH₂)₂, or 2'-DMAEOE nucleoside amidites) are prepared as follows. Other nucleoside amidites are prepared similarly. 2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl]-5-methyl uridine

[00133] 2[2-(Dimethylamino)ethoxylethanol (Aldrich, 6.66 g, 50 mmol) is slowly added to a solution of borane in tetrahydrofuran (1 M, 10 mL, 10 mmol) with stirring in a 100 mL bomb. Hydrogen gas evolves as the solid dissolves. O²-, 2' - anhydro-5-methyluridine (1.2 g, 5 mmol), and sodium bicarbonate (2.5 mg) are added and the bomb is sealed, placed in an oil bath, and heated to 155°C for 26 hours. The bomb is cooled to room temperature and opened. The crude solution is concentrated and the residue partitioned between water (200 mL) and hexanes (200 mL). The excess phenol is extracted into the hexane layer. The aqueous layer is extracted with ethyl acetate (3x200 mL) and the combined organic layers are washed once with water, dried over anhydrous sodium sulfate and concentrated. The residue is columned on silica gel using methanol/methylene chloride 1:20 (which has 2% triethylamine) as the eluent. As the column fractions are concentrated a colorless solid forms which is collected to give the title compound as a white solid.

5'-O-dimethoxytrityI-2'-O-[2(2-N,N-dimethylaminoethoxy) ethyl)]-5- methyl uridine

[00134] To 0.5 g (1.3 mmol) of 2'-O-[2(2-N,N- dimethylaminoethoxy)ethyl)l-5-methyl uridine in anhydrous pyridine (8 mL), triethylamine (0.36 mL) and dimethoxytrityl chloride (DMT-Cl, 0.87 g, 2 eq.) are added and stirred for 1 hour. The reaction mixture is poured into water (200 mL) and extracted with CH₂CI₂ (2x200 mL). The combined CH₂CI2 layers are washed with saturated NaHCO₃ solution, followed by saturated NaCl solution and dried over anhydrous sodium sulfate. Evaporation of the solvent followed by silica gel chromatography using MeOH: CH₂Cl₂:Et₃N (20:1, v/v, with 1% triethylamine) gives the title compound.

5'-O-Dimethoxytrityl-2'-O-[2(2-N,N-dimethylaminoethoxy)ethyl)]-5- methyl uridine-3'-O-(cyanoethyl-N,N-diisopropyl)phosphoramidite [00135] Diisopropylaminotetrazolide (0.6 g) and 2-cyanoethoxyN,N- diisopropyl phosphoramidite (1.1 mL, 2 eq.) are added to a solution of 5'-O- dimefhoxytrityl-2 ' -O- [2(2-N,N-dimethylaminoethoxy)ethyl)] -5 - methyluridine (2.17 g, 3 mmol) dissolved in CH₂CI₂ (20 mL) under an atmosphere of argon. The reaction mixture is stirred overnight and the solvent evaporated. The resulting residue is purified by silica gel flash column chromatography with ethyl acetate as the eluent to give the title compound.

Example 2 Oligonucleotide synthesis

[00136] Unsubstituted and substituted phosphodiester (P=O) oligonucleotides are synthesized on an automated DNA synthesizer (Applied Biosystems model 380B) using standard phosphoramidite chemistry with oxidation by iodine. [00137] Phosphorothioates (P=S) are synthesized as for the phosphodiester oligonucleotides except the standard oxidation bottle is replaced by 0.2 M solution of 3H-l,2-benzodithiole-3-one 1,1 -dioxide in acetonitrile for the stepwise thiation of the phosphite linkages. The thiation wait step is increased to 68 sec and is followed by the capping step. After cleavage from the CPG column and deblocking in concentrated ammonium hydroxide at 55°C (18 h), the oligonucleotides are purified by precipitating twice with 2.5 volumes of ethanol from a 0.5 M NaCl solution. Phosphinate oligonucleotides are prepared as described in U.S. Patent 5,508,270, herein incoφorated by reference. [00138] Alkyl phosphonate oligonucleotides are prepared as described in U.S. Patent 4,469,863, herein incoφorated by reference. [00139] 3 '-Deoxy-3 '-methylene phosphonate oligonucleotides are prepared as described in U.S. Patents 5,610,289 or 5,625,050, herein incoφorated by reference. [00140] Phosphoramidite oligonucleotides are prepared as described in U.S. Patent, 5,256,775 or U.S. Patent 5,366,878, herein incoφorated by reference.

[00141] Alkylphosphonothioate oligonucleotides are prepared as described in WO 94/17093 and WO 94/02499 herein incoφorated by reference.

[00142] 3 '-Deoxy-3 '-amino phosphoramidate oligonucleotides are prepared as described in U.S. Patent 5,476,925, herein incoφorated by reference. [00143] Phosphotriester oligonucleotides are prepared as described in

U.S. Patent 5,023,243, herein incoφorated by reference. [00144] Borano phosphate oligonucleotides are prepared as described in U.S. Patents 5,130,302 and 5,177,198, both herein incoφorated by reference.

Example 3

Oligonucleoside Synthesis

[00145] Methylenemethylimino linked oligonucleosides, also identified as MMI linked oligonucleosides, methylenedimethylhydrazo linked oligonucleosides, also identified as MDH linked oligonucleosides, and methylenecarbonylamino linked oligonucleosides, also identified as amide-3 linked oligonucleosides, and methyleneaminocarbonyl linked oligonucleosides, also identified as amide-4 linked oligonucleosides, as well as mixed backbone compounds having, for instance, alternating MMI and P=O or P=S linkages are prepared as described in U.S. Patents 5,378,825; 5,386,023; 5,489,677; 5,602,240; and 5,610,289, all of which are herein incoφorated by reference.

[00146] Formacetal and thioformacetal linked oligonucleosides are prepared as described in U.S. Patents 5,264,562 and 5,264,564, herein incoφorated by reference.

[00147] Ethylene oxide linked oligonucleosides are prepared as described in U.S. Patent 5,223,618, herein incoφorated by reference.

Example 4 PNA Synthesis

[00148] Peptide nucleic acids (PNAs) are prepared in accordance with any of the various procedures referred to in Peptide Nucleic Acids (PNA): Synthesis, Properties and Potential Applications, Bioorganic & Medicinal Chemistry, 1996, 4, 523. They may also be prepared in accordance with U.S. Patents 5,539,082; 5,700,922; and 5,719,262, herein incoφorated by reference.

Example 5

Synthesis of Chimeric Oligonucleotides [00149] Chimeric oligonucleotides, oligonucleosides or mixed oligonucleotides/oligonucleosides of the invention can be of several different types. These include a first type wherein the "gap" segment of linked nucleosides is positioned between 5' and 3' "wing" segments of linked nucleosides and a second "open end" type wherein the "gap" segment is located at either the 3' or the 5' terminus of the oligomeric compound. Oligonucleotides of the first type are also known in the art as "gapmers" or gapped oligonucleotides. Oligonucleotides of the second type are also known in the art as "hemimers" or "wingmers". [2'-O-Me]^«[2'-deoxy]~[2'-O-Me] Chimeric Phosphorothioate Oligonucleotides

[00150] Chimeric oligonucleotides having 2'-O-alkyl phosphorothioate and 2'-deoxy phosphorothioate oligonucleotide segments are synthesized using an Applied Biosystems automated DNA synthesizer Model 380B, as above. Oligonucleotides are synthesized using the automated synthesizer and 2'-deoxy-5'-dimethoxytrityl-3'-O- phosphoramidite for the DNA portion and 5'-dimethoxytrityl-2'-O-methyl- 3'-O-phosphoramidite for 5' and 3' wings. The standard synthesis cycle is modified by increasing the wait step after the delivery of tetrazole and base to 600 s repeated four times for RNA and twice for 2'-O-methyl. The fully protected oligonucleotide is cleaved from the support and the phosphate group is deprotected in 3: 1 ammonia/ethanol at room temperature overnight then lyophilized to dryness. Treatment in methanolic ammonia for 24 hrs at room temperature is then done to deprotect all bases and sample is again lyophilized to dryness. The pellet is resuspended in IM TBAF in THF for 24 hrs at room temperature to deprotect the 2' positions. The reaction is then quenched with IM TEAA and the sample is then reduced to 1/2 volume by rotovac before being desalted on a G25 size exclusion column. The oligo recovered is then analyzed spectrophotometrically for yield and for purity by capillary electrophoresis and by mass spectrometry. [2'-O-(2-Methoxyethyl)]--[2'-deoxy]-[2'-O-(Methoxyethyl)] Chimeric Phosphorothioate Oligonucleotides

[00151] [2'-O-(2-methoxyethyl)]-[2'-deoxy]— [-2'-O-

(methoxyethyl)] chimeric phosphorothioate oligonucleotides are prepared as per the procedure above for the 2'-O-methyl chimeric oligonucleotide, with the substitution of phorothioate oligonucleotides are prepared as per the procedure above 2'-O-(methoxyethyl) amidites for the 2'-O-methyl amidites. [2'-O-(2-Methoxyethyl)Phosphodiester]— [2'-deoxy Phosphorothioate]— [2'-O-(2 -Methoxyethyl)] Phosphodiester] Chimeric Oligonucleotides [00152] [2'-O-(2-methoxyethyl phosphodiester]-[2'-deoxy phosphorothioate] - [2 ' -O-(methcixyethyl) phosphodiester] chimeric oligonucleotides are prepared as per the above procedure for the 2'-O- methyl chimeric oligonucleotide with the substitution of 2'-O- (methoxyethyl) amidites for the 2'-O-methyl amidites, oxidization with iodine to generate the phosphodiester internucleotide linkages within the wing portions of the chimeric structures and sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) to generate the phosphorothioate internucleotide linkages for the center gap. [00153] Other chimeric oligonucleotides, chimeric oligonucleosides and mixed chimeric oligonucleotides/oligonucleosides are synthesized according to United States patent 5,623,065, herein incoφorated by reference.

Example 6 Oligonucleotide Isolation

[00154] After cleavage from the controlled pore glass column

(Applied Biosystems) and deblocking in concentrated ammonium hydroxide at 55°C for 18 hours, the oligonucleotides or oligonucleosides are purified by precipitation twice out of 0.5 M NaCl with 2.5 volumes ethanol. Synthesized oligonucleotides are analyzed by polyacrylamide gel electrophoresis on denaturing gels and judged to be at least 85% full-length material. The relative amounts of phosphorothioate and phosphodiester linkages obtained in synthesis are periodically checked by "P nuclear magnetic resonance spectroscopy, and for some studies oligonucleotides are purified by HPLC, as described by Chiang et al., J. Biol. Chem. 1991, 266, 18162-18171.

Example 7 Oligonucleotide Synthesis - 96 Well Plate Format

[00155] Oligonucleotides are synthesized via solid phase P(III) phosphoramidite chemistry on an automated synthesizer capable of assembling 96 sequences simultaneously in a standard 96 well format. Phosphodiester internucleotide linkages are afforded by oxidation with aqueous iodine. Phosphorothioate internucleotide linkages are generated by sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) in anhydrous acetonitrile. Standard base-protected beta- cyanoethyldiisopropyl phosphoramidites can be purchased from commercial vendors (e.g. PE-Applied Biosystems, Foster City, CA, or Pharmacia, Piscataway, NJ). Non-standard nucleosides are synthesized as per known literature or patented methods. They are utilized as base protected betacyanoethyldiisopropyl phosphoramidites.

[00156] Oligonucleotides are cleaved from support and deprotected with concentrated NH OH at elevated temperature (55-60°C) for 12-16 hours and the released product then dried in vacuo. The dried product is then re-suspended in sterile water to afford a master plate from which all analytical and test plate samples are then diluted utilizing robotic pipettors.

Example 8 Oligonucleotide Analysis - 96 Well Plate Format

[00157] The concentration of oligonucleotide in each well is assessed by dilution of samples and UV absoφtion spectroscopy. The full-length integrity of the individual products is evaluated by capillary electrophoresis (CE) in either the 96 well format (Beckman P/ACE™ MDQ) or, for individually prepared samples, on a commercial CE apparatus (e.g.,

Beckman P/ACE™ 5000, ABI 270). Base and backbone composition is confirmed by mass analysis of the compounds utilizing electrospray-mass spectroscopy. All assay test plates are diluted from the master plate using single and multi-channel robotic pipettors. Plates are judged to be acceptable if at least 85% of the compounds on the plate are at least 85%> full length.

Example 9

Cell culture and oligonucleotide treatment [00158] The effect of antisense compounds on target nucleic acid expression can be tested in any of a variety of cell types provided that the target nucleic acid is present at measurable levels. This can be routinely determined using, for example, PCR or Northern blot analysis. The following 6 cell types are provided for illustrative puφoses, but other cell types can be routinely used, provided that the target is expressed in the cell type chosen. This can be readily determined by methods routine in the art, for example Northern blot analysis, Ribonuclease protection assays, or RT- PCR. T-24 cells:

[00159] The human transitional cell bladder carcinoma cell line T-24 is obtained from the American Type Culture Collection (ATCC) (Manassas, VA). T-24 cells are routinely cultured in complete McCoy's 5A basal media (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis.

[00160] For Northern blotting or other analysis, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. A549 cells: [00161] The human lung carcinoma cell line A549 can be obtained from the American Type Culture Collection (ATCC) (Manassas, VA). A549 cells are routinely cultured in DMEM basal media (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD), penicillin 100 units per mL, and streptomycin 100 micrograms per mL (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90% confluence. NHDF cells: [00162] Human neonatal dermal fibroblast (NHDF) can be obtained from the Clonetics Coφoration (Walkersville MD). NHDFs are routinely maintained in Fibroblast Growth Medium (Clonetics Coφoration, Walkersville MD) supplemented as recommended by the supplier. Cells are maintained for up to 10 passages as recommended by the supplier. HEK cells:

[00163] Human embryonic keratinocytes (HEK) can be obtained from the Clonetics Coφoration (Walkersville MD). HEKs are routinely maintained in Keratinocyte Growth Medium (Clonetics Coφoration, Walkersville MD) formulated as recommended by the supplier. Cells are routinely maintained for up to 10 passages as recommended by the supplier. MCF-7 cells:

[00164] The human breast carcinoma cell line MCF-7 is obtained from the American Type Culture Collection (Manassas, VA). MCF-7 cells are routinely cultured in DMEM low glucose (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 10% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 7000 cells/well for use in RT-PCR analysis. [00165] For Northern blotting or other analyses, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. LA4 cells: [00166] The mouse lung epithelial cell line LA4 is obtained from the American Type Culture Collection (Manassas, VA). LA4 cells are routinely cultured in F12K medium (Gibco/Life Technologies, Gaithersburg, MD) supplemented with 15% fetal calf serum (Gibco/Life Technologies, Gaithersburg, MD). Cells are routinely passaged by trypsinization and dilution when they reached 90% confluence. Cells are seeded into 96-well plates (Falcon-Primaria #3872) at a density of 3000-6000 cells/ well for use in RT-PCR analysis.

[00167] For Northern blotting or other analyses, cells may be seeded onto 100 mm or other standard tissue culture plates and treated similarly, using appropriate volumes of medium and oligonucleotide. Treatment with antisense compounds:

[00168] When cells reached 80%> confluence, they are treated with oligonucleotide. For cells grown in 96-well plates, wells are washed once with 200 μL OPTI-MEM™-l reduced-serum medium (Gibco BRL) and then treated with 130 μL of OPTI-MEM™-l containing 3.75 μg/mL LIPOFECTIN™ (Gibco BRL) and the desired concentration of oligonucleotide. After 4-7 hours of treatment, the medium is replaced with fresh medium. Cells are harvested 16-24 hours after oligonucleotide treatment.

[00169] The concentration of oligonucleotide used varies from cell line to cell line. To determine the optimal oligonucleotide concentration for a particular cell line, the cells are treated with a positive control oligonucleotide at a range of concentrations.

Example 10 Analysis of oligonucleotide inhibition of ACSl expression

[00170] Antisense modulation of ACSl expression can be assayed in a variety of ways known in the art. For example, ACSl mRNA levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or real-time PCR (RT-PCR). Real-time quantitative PCR is presently preferred. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. Methods of RNA isolation are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1 , pp. 4.1.1-4.2.9 and 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Northern blot analysis is routine in the art and is taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1 , pp. 4.2.1- 4.2.9, John Wiley & Sons, Inc., 1996. Real-time quantitative (PCR) can be conveniently accomplished using the commercially available ABI PRISM™ 7700 Sequence Detection System, available from PE-Applied Biosystems, Foster City, CA and used according to manufacturer's instructions. Prior to quantitative PCR analysis, primer-probe sets specific to the target gene being measured are evaluated for their ability to be "multiplexed" with a GAPDH amplification reaction. In multiplexing, both the target gene and the internal standard gene GAPDH are amplified concurrently in a single sample. In this analysis, mRNA isolated from untreated cells is serially diluted. Each dilution is amplified in the presence of primer-probe sets specific for GAPDH only, target gene only ("single-plexing"), or both (multiplexing). Following PCR amplification, standard curves of GAPDH and target mRNA signal as a function of dilution are generated from both the single-plexed and multiplexed samples. If both the slope and correlation coefficient of the GAPDH and target signals generated from the multiplexed samples fall within 10%> of their corresponding values generated from the single-plexed samples, the primer-probe set specific for that target is deemed as multiplexable. Other methods of PCR are also known in the art. [00171] Protein levels of ACSl can be quantitated in a variety of ways well known in the art, such as immunoprecipitation, Western blot analysis (immunoblotting), ELISA or fluorescence-activated cell sorting (FACS). Antibodies directed to ACSl can be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Coφoration, Birmingham, MI), or can be prepared via conventional antibody generation methods. Methods for preparation of polyclonal antisera are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.12.1-11.12.9, John Wiley & Sons, Inc., 1997. Preparation of monoclonal antibodies is taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.4.1-11.1 1.5, John Wiley Sons, Inc., 1997. [00172] Immunoprecipitation methods are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 10.16.110.16.1 1, John Wiley & Sons, Inc., 1998. Western blot (immunoblot) analysis is standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in

Molecular Biology, Volume 2, pp. 10.8.1-10.8.21, John Wiley Sons, Inc., 1997. Enzyme-linked immunosorbent assays (ELISA) are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.2.1-11.2.22, John Wiley & Sons, Inc., 1991.

Example 11

Poly(A)+ mRNA isolation

[00173] Poly(A)+ mRNA is isolated according to Miura et al., Clin. Chem., 1996, 42, 1758-1764. Other methods for poly(A)+ mRNA isolation are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 1, pp. 4.5.1-4.5.3, John Wiley & Sons, Inc., 1993. Briefly, for cells grown on 96-well plates, growth medium is removed from the cells and each well is washed with 200 μL cold PBS. 60μL lysis buffer (10 mM Tris-HCI, pH 7.6, 1 mM EDTA, 0.5 M NaCl, 0.5% NP-40, 20 mM vanadyl-ribonucleoside complex) is added to each well, the plate is gently agitated and then incubated at room temperature for five minutes. 55 μL of lysate is transferred to Oligo d(T) coated 96-well plates (AGCT Inc., Irvine CA). Plates are incubated for 60 minutes at room temperature, washed 3 times with 200 μL of wash buffer (10 mM Tris-HCI pH 7.6, 1 mM EDTA, 0.3 M NaCl). After the final wash, the plate is blotted on paper towels to remove excess wash buffer and then air-dried for 5 minutes. 60 pL of elution buffer (5 mM Tris-HCI pH 7.6), preheated to 70»C is added to each well, the plate is incubated on a 90»C hot plate for 5 minutes, and the eluate is then transferred to a fresh 96-well plate.

[00174] Cells grown on 100 mm or other standard plates may be treated similarly, using appropriate volumes of all solutions.

Example 12 Total RNA Isolation

[00175] Total mRNA is isolated using an RNEASY 96^™ kit and buffers purchased from Qiagen Inc. (Valencia CA) following the manufacturer's recommended procedures. Briefly, for cells grown on 96- well plates, growth medium is removed from the cells and each well is washed with 200 μL cold PBS. 100 μL Buffer RLT is added to each well and the plate vigorously agitated for 20 seconds. 100 μL of 70% ethanol is then added to each well and the contents mixed by pipetting three times up and down. The samples are then transferred to the RNEASY 96^™ well plate attached to a QIAVAC^™ manifold fitted with a waste collection tray and attached to a vacuum source. Vacuum is applied for 15 seconds. 1 mL of Buffer RW1 is added to each well of the RNEASY 96^™ plate and the vacuum again applied for 15 seconds. 1 mL of Buffer RPE is then added to each well of the RNEASY 96^™ plate and the vacuum applied for a period of 15 seconds. The Buffer RPE wash is then repeated and the vacuum is applied for an additional 10 minutes. The plate is then removed from the QIANAC^™ manifold and blotted dry on paper towels. The plate is then re- attached to the QIANAC^™ manifold fitted with a collection tube rack containing 1.2 mL collection tubes. RΝA is then eluted by pipetting 60μL water into each well, incubating one minute, and then applying the vacuum for 30 seconds. The elution step is repeated with an additional 60μL water. [00176] The repetitive pipetting and elution steps may be automated using a QIAGEΝ Bio-Robot 9604 (Qiagen, Inc., Valencia CA). Essentially, after lysing of the cells on the culture plate, the plate is transferred to the robot deck where the pipetting, DΝase treatment and elution steps are carried out.

Example 13

Real-time Quantitative PCR Analysis of ACSl mRΝA Levels

[00177] Quantitation of ACSl mRΝA levels is determined by real- time quantitative PCR using the ABI PRISM^™ 7700 Sequence Detection System (PE-Applied Biosystems, Foster City, CA) according to manufacturer's instructions. This is a closed-tube, non-gel-based, fluorescence detection system which allows high-throughput quantitation of polymerase chain reaction (PCR) products in real-time. As opposed to standard PCR, in which amplification products are quantitated after the PCR is completed, products in real-time quantitative PCR are quantitated as they accumulate. This is accomplished by including in the PCR reaction an oligonucleotide probe that anneals specifically between the forward and reverse PCR primers, and contains two fluorescent dyes. A reporter dye (e.g., JOE, FAM , or VIC, obtained from either Operon Technologies Inc., Alameda, CA or PE-Applied Biosystems, Foster City, CA) is attached to the 5' end of the probe and a quencher dye (e.g., TAMRA, obtained from either Operon Technologies Inc., Alameda, CA or PE-Applied Biosystems, Foster City, CA) is attached to the 3' end of the probe. When the probe and dyes are intact, reporter dye emission is quenched by the proximity of the 3' quencher dye. During amplification, annealing of the probe to the target sequence creates a substrate that can be cleaved by the 5'-exonuclease activity of Taq polymerase. During the extension phase of the PCR amplification cycle, cleavage of the probe by Taq polymerase releases the reporter dye from the remainder of the probe (and hence from the quencher moiety) and a sequence-specific fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes, and the fluorescence intensity is monitored at regular intervals by laser optics built into the ABI PRISM " 7700 Sequence Detection System. In each assay, a series of parallel reactions containing serial dilutions of mRNA from untreated control samples generates a standard curve that is used to quantitate the percent inhibition after antisense oligonucleotide treatment of test samples. [00178] PCR reagents can be obtained from PE-Applied Biosystems, Foster City, CA. RT-PCR reactions are carried out by adding 25 μL PCR cocktail (lx TAQMAN™ buffer A, 5.5 MM MgCl₂, 300 μM each of dATP, dCTP and dGTP, 600 μM of dUTP, 100 nM each of forward primer, reverse primer, and probe, 20 Units RNAse inhibitor, 1.25 Units AMPLITAQ GOLD^™, and 12.5 Units MuLN reverse transcriptase) to 96 well plates containing 25 μL poly(A) mRΝA solution. The RT reaction is carried out by incubation for 30 minutes at 48°C. Following a 10 minute incubation at 95°C to activate the AMPLITAQ GOLD^™, 40 cycles of a two-step PCR protocol are carried out: 95 ^°C for 15 seconds (denaturation) followed by 60^°C for 1.5 minutes (annealing/extension). [00179] Probes and primers to human ACSl were designed to hybridize to a human ACSl sequence, using published sequence, information (GenBank accession number NM_021122, incoφorated herein as Figure 1. For human ACSl the PCR primers were: forward primer: TCTGCCACTGTGCTGACGTT SEQ ID NO : 3619 reverse primer: ACTCTGTCTGTCCGTATCCTTCATAA SEQ ID

NO : 3620 and the PCR probe is: FAM™-

CTCAGAGCAGCCCTGGGCTGTCAGT SEQ ID NO : 3621 -TAMRA where FAM™ (PE-Applied Biosystems, Foster City, CA) is the fluorescent reporter dye) and TAMRA (PE-Applied Biosystems, Foster City, CA) is the quencher dye. For human cyclophilin the PCR primers were: forward primer: CCCACCGTGTTCTTCGACAT SEQ ID NO : 3622 reverse primer: TTTCTGCTGTCTTTGGGACCTT SEQ ID NO : 3623 and the PCR probe is: 5' JOE- CGCGTCTCCTTTGAGCTGTTTGCA SEQ ID NO : 3624 - TAMRA 3' where JOE (PE-Applied Biosystems, Foster City, CA) is the fluorescent reporter dye) and TAMRA (PE-Applied Biosystems, Foster City, CA) is the quencher dye. Example 14

Antisense inhibition of human ACSl expression by chimeric phosphorothioate oligonucleotides having 2'-MOE wings and a deoxy

gap [00180] In accordance with the present invention, a series of oligonucleotides are designed to target different regions of the human ACSl RNA, using published sequences (NM 021122) incoφorated herein as Figure 1. The oligonucleotides are shown in Table 3. "Position" indicates the first (5 '-most) nudeotide number on the particular target sequence to which the oligonucleotide binds. The indicated parameters for each oligo were predicted using RNAstructure 3.7 by David H. Mathews, Michael Zuker, and Douglas H. Turner. The parameters are described either as free energy (The energy that is released when a reaction occurs. The more negative the number, the more likely the reaction will occur. All free energy units are in kcal/mol.) or melting temperature (the temperature at which two anneal strands of polynucleic acid separate. The higher the temperature, greater the affinity between the 2 strands.) When designing an antisense oligonucleotide (oligomers) that will bind with high affinity, it is desirable to consider the structure of the target RNA strand and the antisense oligomer. Specifically, for an oligomer to bind tightly (in the table described as 'duplex formation'), it should be complementary to a stretch of target RNA that has little self-structure (in the table the free energy of which is described as 'target structure'). Also, the oligomer should have little self- structure, either intramolecular (in the table the free energy of which is described as 'intramolecular oligo') or bimolecular (in the table the free TABLE 3 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo GTATTCTCCTTGTGCCAGCT

1695 SEQ ID Nθ:l -25.6 -28.1 81.2 -2.5 0 -4.3 GGCTTCAGGGGTTTGGGTCT

152 SEQ ID NO: 2 -25.1 -29 85.1 -3.9 0 -3.8 GCCCAGGCTCGACTGTACTT

1269 SEQ ID NO: 3 -25.1 -29.4 80.3 -3.6 -0.4 -6.9 TCGCATGGCGGCTTCAGGGG

161 SEQ ID NO: 4 -25 -30.2 81 -3.2 -2 -8.1 GTCGCATGGCGGCTTCAGGG

162 SEQ ID NO: 5 -24.7 -30.2 82 -3.2 -2.3 -8.5 TGTATTCTCCTTGTGCCAGC

1696 SEQ ID NO: 6 -24.7 -27.2 78.9 -2.5 0 -3.2 ATTCTCCTTGTGCCAGCTTA

1693 SEQ ID NO: 7 -24.5 -27 77.9 -2.5 0 -4.5 TATTCTCCTTGTGCCAGCTT

1694 SEQ ID NO: 8 -24.5 -27 77.9 -2.5 0 -4.5 GCATGGCGGCTTCAGGGGTT

159 SEQ ID NO: 9 -24.4 -30.3 83.7 -5.9 0 -5.4 GCTTCAGGGGTTTGGGTCTC

151 SEQ ID NO:3616 -24.3 -28.2 84.3 -3.9 0 -2.8 TGGCGGCTTCAGGGGTTTGG

156 SEQ ID NO: 10 -24.3 -29.1 81 -4.8 0 -6.3 GGTCGCATGGCGGCTTCAGG

163 SEQ ID NO: 11 -23.9 -30.2 82 -3.2 -3.1 -9.4 CGCCCAGGCTCGACTGTACT

1270 SEQ ID NO: 12 -23.8 -30.1 79.5 -5.6 -0.4 -7.2 TTCTCCTTGTGCCAGCTTAA

1692 SEQ ID NO: 13 -23.8 -26.3 75.3 -2.5 0 -4.5 GGCGGCTTCAGGGGTTTGGG

155 SEQ ID NO: 14 -23.7 -30.3 83.9 -6.6 0 -6.3 GCTTCCGTCTGTTGGCTCTT

778 SEQ ID NO: 15 -23.6 -29.1 83.4 -5.5 0 -3.7 CCCAGGCTCGACTGTACTTT

1268 SEQ ID NO: 16 -23.4 -27.7 76.4 -3.6 -0.4 -6.2 CAGGGGCTATGTATTCTCCT

1705 SEQ ID NO: 17 -23.1 -26.3 76.5 -3.2 0 -3.3 TCTCCTTGTGCCAGCTTAAA

1691 SEQ ID NO: 18 -23 -25.5 72.5 -2.5 0 -4.5 GAGGTCGCATGGCGGCTTCA

165 SEQ ID NO: 19 -22.9 -29.6 80.7 -3.2 -3.5 -10.9 CATGGCGGCTTCAGGGGTTT

158 SEQ ID NO: 20 -22.7 -28.6 79.6 -5.9 0 -6.2 AGGTCGCATGGCGGCTTCAG

164 SEQ ID NO: 21 -22.7 -29 79.7 -3.2 -3.1 -9.4 CTCCTTGTGCCAGCTTAAAT

1690 SEQ ID NO: 22 -22.6 -25.1 70.9 -2.5 0 -4.5 TCAGGGGCTATGTATTCTCC

1706 SEQ ID NO: 23 -22.6 -25.8 76.3 -3.2 0 -3.7 GGGCTATGTATTCTCCTTGT

1702 SEQ ID NO: 24 -22.5 -25.7 76.1 -3.2 0 -3.7 GGGGCTATGTATTCTCCTTG

1703 SEQ ID NO: 25 -22.5 -25.7 75.2 -3.2 0 -3.7 AGGGGCTATGTATTCTCCTT

1704 SEQ ID NO: 26 -22.5 -25.7 75.7 -3.2 0 -3.7 CTTCCGTCTGTTGGCTCTTC

777 SEQ ID NO: 27 -22.2 -27.7 80.6 -5.5 0 -3.7

87 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTATGTATTCTCCTTGTGCC 1699 SEQ ID NO:28 -22.1 -25.3 74.2 -3.2 0 -3

GCGGCTTCAGGGGTTTGGGT 154 SEQ ID NO: 29 -21.9 -30.3 85 -8.4 0 -5.3

TATGTATTCTCCTTGTGCCA 1698 SEQ ID NO: 30 -21.9 -25.1 73.4 -3.2 0 -3

GTTAGGCTACCAAGTAGTGT

3459 SEQ ID NO:31 -21.7 -24.1 72.3 -1.3 -0.9 -5.4 ATGGCGGCTTCAGGGGTTTG

157 SEQ ID NO: 32 -21.6 -27.9 78.4 -6.3 0 -6.2

CGGCTTCAGGGGTTTGGGTC

153 SEQ ID NO: 33 -21.5 -28.9 82.3 -7.4 0 -3.8

GGAGAGGTCGCATGGCGGCT

168 SEQ ID NO: 34 -21.4 -30.2 81.7 -5.7 -3.1 -9.4 CCAGGCTCGACTGTACTTTG

1267 SEQ ID NO:35 -21.4 -25.7 72.7 -3.6 -0.4 -6.2

TCCTTGTGCCAGCTTAAATA

1689 SEQ ID NO:36 -21.4 -23.9 68.4 -2.5 0 -4.5

TGGAGAGGTCGCATGGCGGC

169 SEQ ID NO: 37 -21.3 -29.3 79.6 -5.7 -2.3 -8.5 CAGGCTCGACTGTACTTTGT

1266 SEQ ID NO: 38 -21.3 -24.9 72.5 -3.6 0 -5.4

GGCTATGTATTCTCCTTGTG 1701 SEQ ID NO: 39 -21.3 -24.5 73.2 -3.2 0 -3.7

GAGAGGTCGCATGGCGGCTT 167 SEQ ID NO: 40 -21.1 -29.1 79.6 -5.7 -2.3 -8.6

CCGCCCAGGCTCGACTGTAC 1271 SEQ ID NO:41 -21 -31.2 81 -9.7 -0.1 -7.2

CCTTGTGCCAGCTTAAATAT 1688 SEQ ID NO: 42 -21 -23.5 66.9 -2.5 0 -4.5

GGCTTCCGTCTGTTGGCTCT 779 SEQ ID NO: 43 -20.8 -30.2 85.7 -8.9 -0.1 -3.7

TTCAGGGGCTATGTATTCTC

1707 SEQ ID NO: 44 -20.7 -23.9 72.8 -3.2 0 -3.7 TTAGGCTACCAAGTAGTGTT

3458 SEQ ID NO:45 -20.7 -23 69.1 -1.3 -0.8 -5.3

GAGAGTTTATTTTTTGGGGA 3082 SEQ ID NO:46 -20.6 -21 64.8 0 0 -0.9

ATCTTTTCAGGGGCTATGTA 1712 SEQ ID NO: 47 -20.5 -23.6 71.4 -3.1 0 -4.4

TTTCAATCTTTTCAGGGGCT 1717 SEQ ID NO:48 -20.5 -23.6 70.4 -3.1 0 -4.4

AGGCTACCAAGTAGTGTTAT

3456 SEQ ID NO:49 -20.5 -22.9 68.7 -1.3 -0.9 -5.4 AGTTAGGCTACCAAGTAGTG

3460 SEQ ID NO: 50 -20.5 -22.9 69 -1.3 -0.9 -5.4 CGCATGGCGGCTTCAGGGGT

160 SEQ ID NO: 51 -20.4 -31 82.7 -9.1 -1.4 -6.8

TTTCAGGGGCTATGTATTCT

1708 SEQ ID NO:52 -20.4 -23.6 71.4 -3.2 0 -3.7 GCTCATTTTGGAAAGTGTGT

2322 SEQ ID NO:53 -20.4 -22.1 66.6 -1.7 0 -4.3 GGCTCATTTTGGAAAGTGTG

2323 SEQ ID NO: 54 -20.4 -22.1 66 -1.7 0 -4.5 AGGCTCATTTTGGAAAGTGT

2324 SEQ ID NO: 55 -20.4 -22.1 66.3 -1.7 0 -4.5 GTGATGCCTTTGACCTGTTC

1964 SEQ ID NO: 56 -20.3 -26.1 75.3 -5.8 0 -2.3

TAGGCTACCAAGTAGTGTTA

3457 SEQ ID NO: 57 -20.2 -22.6 68.1 -1.3 -0.9 -5.4 GCATGGAGAGGTCGCATGGC

172 SEQ ID NO: 58 -20.1 -28 78.5 -5.7 -2.2 -7.2

88 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo AATCTTTTCAGGGGCTATGT

1713 SEQ ID NO: 59 -20.1 -23.2 69.5 -3.1 0 -4.4 TTCAATCTTTTCAGGGGCTA

1716 SEQ ID NO: 60 -20.1 -23.2 69.5 -3.1 0 -4.4 TCAATCTTTTCAGGGGCTAT

1715 SEQ ID NO: 61 -20 -23.1 69.1 -3.1 0 -4.4 TAGTGCAAGCCCTGTTGTGC

3420 SEQ ID NO: 62 -20 -27.7 78.5 -7 -0.5 -5.4 TTCCGTCTGTTGGCTCTTCC

776 SEQ ID NO: 63 -19.9 -28.8 82.2 -8.9 0 -3.7 TGTGATGCCTTTGACCTGTT

1965 SEQ ID NO: 64 -19.9 -25.7 73.4 -5.8 0 -3 ATGGAGAGGTCGCATGGCGG

170 SEQ ID NO: 65 -19.8 -27.5 75.4 -5.7 -2 -7.7 GTAGGCATCCATGACAACTA

684 SEQ ID NO: 66 -19.8 -23.3 67.6 -2.9 -0.3 -4.5 TGATGCCTTTGACCTGTTCA

1963 SEQ ID NO: 67 -19.8 -25.6 73 -5.8 0 -3.6 ATGTGATGCCTTTGACCTGT

1966 SEQ ID NO: 68 -19.8 -25.6 73 -5.8 0 -3 AAGTTAGGCTACCAAGTAGT

3461 SEQ ID NO: 69 -19.8 -22.2 66.8 -1.3 -0.9 -5.2 CATGGAGAGGTCGCATGGCG

171 SEQ ID NO: 70 -19.7 -27 73.9 -5.7 -1.6 -7.1 TTTTCAATCTTTTCAGGGGC

1718 SEQ ID NO: 71 -19.7 -22.8 68.8 -3.1 0 -2.8 GGCATCCATGACAACTATGA

681 SEQ ID NO: 72 -19.6 -23 65.9 -2.9 -0.1 -5.5 TCCTCTTGGAGGCAAAGTCC

1183 SEQ ID NO: 73 -19.6 -26.4 75.1 -5 -1.8 -7.2 GCTATGTATTCTCCTTGTGC

1700 SEQ ID NO: 74 -19.6 -25.1 75 -5.5 0 -2.8 CAATCTTTTCAGGGGCTATG

1714 SEQ ID NO: 75 -19.6 -22.7 67.3 -3.1 0 -4.4 TGAGAGTTTATTTTTTGGGG

3083 SEQ ID NO: 76 -19.6 -20.4 63.3 -0.6 0 -0.9 CCGTCTGTTGGCTCTTCCCA

774 SEQ ID NO: 77 -19.5 -31 84.4 -11 -0.1 -3.7 TCTTCCGCCCAGGCTCGACT

1275 SEQ ID NO: 78 -19.5 -31.9 83.4 -11.9 -0.1 -7.2 CTCTTCCGCCCAGGCTCGAC

1276 SEQ ID NO: 79 -19.5 -31.9 83.4 -11.9 -0.1 -7.2 CCTCGCCCTCGGCAGCCATG

1510 SEQ ID NO: 80 -19.5 -34.2 85.5 -12.5 -2.2 -8.5 CAGGGTGCAATGTGATGCCT

1975 SEQ ID NO: 81 -19.4 -26.6 74.5 -5.8 -1.3 -6 GATTCTCCAGCCAGGACAGT

2565 SEQ ID NO: 82 -19.4 -27.5 78.5 -7.2 -0.8 -5 GGCTACCAAGTAGTGTTATT

3455 SEQ ID NO: 83 -19.4 -23 68.8 -2.6 -0.9 -5.4 GAAGTTAGGCTACCAAGTAG

3462 SEQ ID NO: 84 -19.4 -21.6 64.8 -1.3 -0.6 -4.7 CTTGCATTGTCCTGTGTTGA

1 SEQ ID NO: 85 -19.3 -25.2 74.1 -5.9 0 -5.1 AGAGTTTATTTTTTGGGGAA

3081 SEQ ID NO: 86 -19.3 -19.7 61.2 0 0 -1.9 CTTCAGGGGTTTGGGTCTCG

150 SEQ ID NO: 87 -19.2 -27.2 78.9 -8 0 -2.4 CTTCGCATGTAGATATTTTC

1733 SEQ ID NO: 88 -19.2 -20.6 63.1 -1.3 0 -4.7 AGGGGTTTGGGTCTCGTGGC

146 SEQ ID NO: 89 -19.1 -29.3 84.4 -10.2 0 -3.1

89 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol

IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TCCGCCCAGGCTCGACTGTA 1272 SEQ ID NO: 90 -19.1 -31.4 82.1 -11.6 -0.4 -7.2

GCAACAGGCTCACTTCGCAT

1745 SEQ ID NO: 91 -19.1 -26.6 74.1 -6.8 -0.5 -4.8

GTTTCCTCTAGCATTCCTAT

2252 SEQ ID NO: 92 -19.1 -25.3 74.8 -6.2 0 -4.1

GTGAGATTCTCCAGCCAGGA

2569 SEQ ID NO: 93 -19.1 -27.2 77.9 -7.2 -0.8 -7.2

GGTCCTTCAAGTAGCCCTGA

1561 SEQ ID NO: 94 -19 -28.4 79.8 -9.4 0 -3.2

AGGCATCCATGACAACTATG

682 SEQ ID NO: 95 -18.9 -22.4 64.9 -2.9 -0.3 -4.5

TCAGGGTGCAATGTGATGCC

1976 SEQ ID NO: 96 -18.9 -26.1 74.2 -5.8 -1.3 -5.4

TGTGAGATTCTCCAGCCAGG

2570 SEQ ID NO: 97 -18.8 -26.6 76.3 -7.2 -0.3 -7.2

CTTTAGTGCAAGCCCTGTTG

3423 SEQ ID NO: 98 -18.8 -25.8 73.5 -7 0.4 -5.4

TTCCGCCCAGGCTCGACTGT

1273 SEQ ID NO: 99 -18.7 -31.8 83 -12.4 -0.4 -7.2

CTCGCCCTCGGCAGCCATGT

1509 SEQ ID NO: 100 -18.7 -33.4 85.8 -12.5 -2.2 -8.5

GTGCAATGTGATGCCTTTGA

1971 SEQ ID NO: 101 -18.7 -24.3 69.9 -4.2 -1.3 -5.4

ATTCTCCAGCCAGGACAGTT

2564 SEQ ID NO: 102 -18.7 -27 77.5 -7.2 -1 -5.2

AGTGCAAGCCCTGTTGTGCT

3419 SEQ ID NO: 103 -18.7 -28.9 81.1 -8.8 -1.3 -6.4

TAGGCATCCATGACAACTAT

683 SEQ ID NO: 104 -18.6 -22.1 64.4 -2.9 -0.3 -4.5

AGGCTCGACTGTACTTTGTG

1265 SEQ ID NO: 105 -18.6 -24.2 71.2 -5.6 0 -4.8

TTCGCATGTAGATATTTTCA

1732 SEQ ID NO: 106 -18.6 -20.4 62.3 -1.3 -0.1 -4.9

GAGATTCTCCAGCCAGGACA

2567 SEQ ID NO: 107 -18.6 -26.9 76.3 -7.2 -1 -6.2

GAGTTTATTTTTTGGGGAAA

3080 SEQ ID NO: 108 -18.6 -19 58.9 0 0 -2.9

TGAAGTTAGGCTACCAAGTA

3463 SEQ ID NO: 109 -18.6 -21.6 64.5 -2.4 -0.3 -4.2

AGCAACAGGCTCACTTCGCA

1746 SEQ ID NO: 110 -18.5 -26.6 74.4 -6.8 -1.2 -5.9

TGTTTCCTCTAGCATTCCTA

2253 SEQ ID NO: 111 -18.5 -25.3 74.7 -6.8 0 -4.1

AAGGCTCATTTTGGAAAGTG

2325 SEQ ID NO: 112 -18.5 -20.2 61 -1.7 0 -4.5

AGCCAGGACAGTTGTTCTTA

2557 SEQ ID NO: 113 -18.5 -24.9 74 -6.4 0 -4.7

TCTTTAGTGCAAGCCCTGTT

3424 SEQ ID NO: 114 -18.5 -26.2 75.4 -7 -0.4 -5.4

TTCTTTAGTGCAAGCCCTGT

3425 SEQ ID NO: 115 -18.5 -26.2 75.4 -7 -0.4 -5.4

GCATCCATGACAACTATGAT

680 SEQ ID NO: 116 -18.4 -21.8 63.5 -2.9 -0.1 -5.5

CATGAAGGCCATCAGCAGGA

2159 SEQ ID NO: 117 -18.4 -25.7 72.1 -5.8 -1.4 -9.7

ACAATTTTTAAGGCTCATTT

2334 SEQ ID NO: 118 -18.4 -18.8 58.3 0 0 -3.7

GAGTGAGTGGTTCAGTGAAG

2991 SEQ ID NO: 119 -18.4 -22.3 68.8 -3.2 -0.5 -8

AGAGTGAGTGGTTCAGTGAA

2992 SEQ ID NO: 120 -18.4 -22.3 68.8 -3.2 -0.5 -7.9

90 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TTTAGTGCAAGCCCTGTTGT

3422 SEQ ID NO: 121 -18.4 -26.1 75 -7 -0.4 -4.9 TGCATGGAGAGGTCGCATGG

173 SEQ ID NO: 122 -18.3 -26.2 73.9 -5.7 -2.2 -7.2 CCTCTTGGAGGCAAAGTCCA

1182 SEQ ID NO: 123 -18.3 -26.7 74.5 -7.1 -1.2 -7.8 TTCTTTCCTCTTGGAGGCAA

1188 SEQ ID NO: 124 -18.3 -25.1 73.3 -5 -1.8 -8.4 ACTGACAGCCCAGGGCTGCT

1354 SEQ ID NO: 125 -18.3 -30.9 83.8 -8.3 -3.6 -16.5 CTCATTTTGGAAAGTGTGTA

2321 SEQ ID NO: 126 -18.3 -20 61.7 -1.7 0 -4.3 CAATTTTTAAGGCTCATTTT

2333 SEQ ID NO: 127 -18.3 -18.7 58.1 0 0 -3.7 TTAGTGCAAGCCCTGTTGTG

3421 SEQ ID NO: 128 -18.3 -26 74.4 -7 -0.4 -5.4 GCTTGCATTGTCCTGTGTTG

2 SEQ ID NO: 129 -18.2 -26.4 77.3 -8.2 0 -5.1 TTTTCAGGGGCTATGTATTC

1709 SEQ ID NO: 130 -18.2 -22.8 69.7 -4.6 0 -3.7 TAAGGCTCATTTTGGAAAGT

2326 SEQ ID NO: 131 -18.2 -19.9 60.5 -1.7 0 -4.3 CCAGCCAGGACAGTTGTTCT

2559 SEQ ID NO: 132 -18.2 -27.8 79.1 -9.6 0 -4.5 GTGCAAGCCCTGTTGTGCTT

3418 SEQ ID NO: 133 -18.2 -29 81.1 -9.4 -1.3 -6.4 CGGTCGATAATTTTCAAGGT

1658 SEQ ID NO: 134 -18.1 -21.1 61.8 -3 0 -5 TTTCCGGTCGATAATTTTCA

1662 SEQ ID NO: 135 -18.1 -22 63.8 -3.9 0 -6.6 ATGTGCTTTTTCCGGTCGAT

1670 SEQ ID NO: 136 -18.1 -25.7 72.5 -7.6 0 -6.6 ATGTATTCTCCTTGTGCCAG

1697 SEQ ID NO: 137 -18.1 -25.4 74.3 -7.3 0 -3.2 GATGCCTTTGACCTGTTCAA

1962 SEQ ID NO: 138 -18.1 -24.9 70.8 -5.8 -0.9 -4.8 CAGGGGTTTGGGTCTCGTGG

147 SEQ ID NO: 139 -18 -28.2 80.7 -10.2 0 -3 TTCAGGGGTTTGGGTCTCGT

149 SEQ ID NO: 140 -18 -27.5 80.6 -9.5 0 -3 CTGACAGCCCAGGGCTGCTC

1353 SEQ ID NO: 141 -18 -31.1 85 -8.3 -4.5 -17.4 CCCTCGGCAGCCATGTAATT

1505 SEQ ID NO: 142 -18 -28.6 76 -10.1 0 -8 TGAAGGCCATCAGCAGGAGA

2157 SEQ ID NO: 143 -18 -25.6 72.6 -6.7 -0.6 -8.9 ACATGAAGGCCATCAGCAGG

2160 SEQ ID NO: 144 -18 -25.3 71.4 -5.8 -1.4 -9.7 TTTTAAGGCTCATTTTGGAA

2329 SEQ ID NO: 145 -18 -19.7 60.3 -1.7 0 -4.3 TACAATTTTTAAGGCTCATT

2335 SEQ ID NO: 146 -18 -18.4 57.4 0 0 -3.7 TTACAATTTTTAAGGCTCAT

2336 SEQ ID NO: 147 -18 -18.4 57.4 0 0 -3.7 AGATTCTCCAGCCAGGACAG

2566 SEQ ID NO: 148 -18 -26.3 75.2 -7.2 -1 -5.2 TGGGCTTCCGTCTGTTGGCT

781 SEQ ID NO: 149 -17.9 -30.1 84.1 -11 -1.1 -5.1 AATGTGATGCCTTTGACCTG

1967 SEQ ID NO: 150 -17.9 -23.7 67.5 -5.8 0 -3 TTTCCTCTAGCATTCCTATG

2251 SEQ ID NO: 151 -17.9 -24.1 71.1 -6.2 0 -4.1 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo ninding ation Duplex ture oligo oligo

GGACAGTTGTTCTTATTTTT 2552 SEQ ID NO: 152 -17.9 -20.8 65.2 -2.9 0 -3.6

CAGCCAGGACAGTTGTTCTT 2558 SEQ ID NO: 153 -17.9 -25.9 75.8 -8 0 -4.5

TGAGATTCTCCAGCCAGGAC 2568 SEQ ID NO: 154 -17.9 -26.2 75 -7.2 -1 -7.2

TGTGCTTTTTCCGGTCGATA 1669 SEQ ID NO:155 -17.8 -25.4 71.9 -7.6 0 -6.6

TATGTGCTTTTTCCGGTCGA 1671 SEQ ID NO:156 -17.8 -25.4 71.9 -7.6 0 -6.6

TCGCATGTAGATATTTTCAA 1731 SEQ ID NO: 157 -17.8 -19.6 59.9 -1.3 -0.1 -4.9

GGTGCAATGTGATGCCTTTG 1972 SEQ ID NO:158 -17.8 -24.9 71.1 -5.7 -1.3 -5.4

ATTAACAACATGAAGGCCAT 2167 SEQ ID NO: 159 -17.8 -19.8 58.3 -1.5 0 -7.7

GACTGCATGGAGAGGTCGCA 176 SEQ ID NO: 160 -17.7 -26.7 75.4 -8.4 -0.3 -5.2

TCTGTTGGCTCTTCCCAGGT

771 SEQ ID NO: 161 -17.7 -29.4 84.7 -11 -0.5 -4.4 GTCTGTTGGCTCTTCCCAGG

772 SEQ ID NO: 162 -17.7 -29.4 84.7 -11 -0.5 -4.4 TTCCTCTTGGAGGCAAAGTC

1184 SEQ ID NO: 163 -17.7 -24.5 71.8 -5 -1.8 -8.4

TCTTTCCTCTTGGAGGCAAA 1187 SEQ ID NO: 164 -17.7 -24.3 70.5 -5 -1.6 -8.4

ACTCTTCCGCCCAGGCTCGA 1277 SEQ ID NO: 165 -17.7 -31.9 83.4 -13.7 -0.1 -7.2

GGCTCACTTCGCATGTAGAT 1739 SEQ ID NO: 166 -17.7 -25.4 73.4 -7 -0.5 -4.8

ATGAAGGCCATCAGCAGGAG 2158 SEQ ID NO: 167 -17.7 -25 71.3 -5.8 -1.4 -9.7

TTCCTCTAGCATTCCTATGA 2250 SEQ ID NO: 168 -17.7 -24.6 72.1 -6.2 -0.4 -4.1

TTGTGAGATTCTCCAGCCAG 2571 SEQ ID NO: 169 -17.7 -25.5 74.1 -7.2 -0.3 -7.4

CCCATTTGCCAGAGGCTCCT 2769 SEQ ID NO: 170 -17.7 -31.2 83.3 -11.4 -2.1 -7.5

CCCTCGCCCTCGGCAGCCAT 1511 SEQ ID NO: 171 -17.6 -36.2 88.8 -16.9 -1.7 -8.5

TCCTCTAGCATTCCTATGAG 2249 SEQ ID NO: 172 -17.6 -24.5 72 -6.2 -0.5 -4.1

CCGCTTGTGAGATTCTCCAG 2575 SEQ ID NO: 173 -17.6 -26.5 74.4 -8.2 -0.4 -7.7

AAACCAGAGAGAGTTCAGCT 589 SEQ ID NO: 174 -17.5 -22.4 66.4 -4.3 -0.3 -4.6

CGTAGGCATCCATGACAACT 685 SEQ ID NO: 175 -17.5 -24.4 68.3 -6.3 -0.3 -4.5

GCCGTAGGCATCCATGACAA

687 SEQ ID NO: 176 -17.5 -27.1 73.4 -5.9 -3.7 -11.9 TGCCGTAGGCATCCATGACA

688 SEQ ID NO: 177 -17.5 -27.8 75.5 -5.9 -4.4 -13.2 CGTCTGTTGGCTCTTCCCAG

773 SEQ ID NO: 178 -17.5 -29 81.3 -11 -0.2 -4.4 TCTGCTTCTTTCCTCTTGGA

1193 SEQ ID NO: 179 -17.5 -26.1 77.4 -7.6 -0.9 -5.4

CGATAATTTTCAAGGTGCCA

1654 SEQ ID NO: 180 -17.5 -22 63.2 -4.5 0 -6.2

CCTCTAGCATTCCTATGAGA

2248 SEQ ID NO: 181 -17.5 -24.7 71.7 -6.2 -0.9 -4.2

ATGAAGTTAGGCTACCAAGT

3464 SEQ ID NO: 182 -17.5 -21.9 65 -3.8 -0.3 -4.2

92 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position ol igo binding ation Duplex ture oligo oligo

ACCAGAGAGAGTTCAGCTTT

587 SEQ ID NO : 183 -17.4 -24 71.9 -6 -0.3 -4.7 TCCGTCTGTTGGCTCTTCCC

775 SEQ ID NO : 184 -17.4 -30.7 85.4 -12.8 -0.1 -3.7

TTTCCTCTTGGAGGCAAAGT 1185 SEQ ID NO: 185 -17.4 -24.2 70.5 -5 -1.8 -8.4

CGCATGTAGATATTTTCAAT 1730 SEQ ID NO: 186 -17.4 -19.2 58.6 -1.3 -0.1 -4.9

ACTTCGCATGTAGATATTTT 1734 SEQ ID NO: 187 -17.4 -20.4 62.2 -3 0 -4.8

TTCAGGGTGCAATGTGATGC 1977 SEQ ID NO: 188 -17.4 -24.2 70.9 -5.8 -0.9 -5.4

TCATTTTGGAAAGTGTGTAT 2320 SEQ ID NO: 189 -17.4 -19.1 59.7 -1.7 0 -4.3

CTGAGAGTTTATTTTTTGGG 3084 SEQ ID NO: 190 -17.4 -20.1 62.6 -2.7 0 -1.5

AACCAGAGAGAGTTCAGCTT

588 SEQ ID NO: 191 -17.3 -23.2 69 -5.3 -0.3 -4.7 TCCGGTTCAGCAGTCTTGGA

1111 SEQ ID NO: 192 -17.3 -27.7 79.4 -10.4 0 -6.6

CCTCGGCAGCCATGTAATTC 1504 SEQ ID NO: 193 -17.3 -27 74.3 -9.1 0 -8.5

GGTCGATAATTTTCAAGGTG 1657 SEQ ID NO: 194 -17.3 -20.3 61.3 -3 0 -5

TTCCGGTCGATAATTTTCAA 1661 SEQ ID NO: 195 -17.3 -21.2 61.5 -3.9 0 -6.6

TTTACAATTTTTAAGGCTCA 2337 SEQ ID NO: 196 -17.3 -18.5 57.8 -1.1 0 -3.7

AGAGGTCGCATGGCGGCTTC 166 SEQ ID NO: 197 -17.2 -28.9 80 -8.5 -3.2 -10.3

GCCATTCATAGGGTTGGTCT 355 SEQ ID NO: 198 -17.2 -26.8 78.2 -9 -0.3 -5.2

TCGATAATTTTCAAGGTGCC 1655 SEQ ID NO: 199 -17.2 -21.7 63.5 -4.5 0 -4.9

TCCGGTCGATAATTTTCAAG 1660 SEQ ID NO:200 -17.2 -21.1 61.4 -3.9 0 -6.6

ATATGTGCTTTTTCCGGTCG 1672 SEQ ID NO:201 -17.2 -24.8 70.6 -7.6 0 -6.6

CGCCTTCATTGTTGGAGTCA 2022 SEQ ID NO: 202 -17.2 -26.2 74.7 -8.5 -0.2 -4.7

TTTAAGGCTCATTTTGGAAA 2328 SEQ ID NO: 203 -17.2 -18.9 58 -1.7 0 -4.3

TTGGGCTTCCGTCTGTTGGC 782 SEQ ID NO: 204 -17.1 -29.3 82.5 -11 -1.1 -5.1

ACACACCTCGCCCTCGCCCT 1521 SEQ ID NO:205 -17.1 -34.7 85.6 -17 -0.3 -2.7

GTGCTTTTTCCGGTCGATAA 1668 SEQ ID NO:206 -17.1 -24.7 69.8 -7.6 0 -6.6

TTCGCCTTCATTGTTGGAGT 2024 SEQ ID NO: 207 -17.1 -25.6 74 -8.5 0.3 -4.2

AATTAACAACATGAAGGCCA 2168 SEQ ID NO:208 -17.1 -19.1 56.5 -1.5 0 -7.7

CATTTTGGAAAGTGTGTATT 2319 SEQ ID NO:209 -17.1 -18.8 58.6 -1.7 0 -3.1

TTAAGGCTCATTTTGGAAAG 2327 SEQ ID NO:210 -17.1 -18.8 57.9 -1.7 0 -3.5

CCCACACCTCTGGCCTCGTT 720 SEQ ID NO: 211 -17 -32.4 84.4 -15.4 0 -7.2

GGGCTTCCGTCTGTTGGCTC 780 SEQ ID NO: 212 -17 -30.5 86.4 -12.8 -0.4 -5.1

GCATGTAGATATTTTCAATC 1729 SEQ ID NO: 213 -17 -18.8 59.3 -1.3 -0.1 -4.9

93 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

>sition oligo binding ation Duplex ture oligo oligo CAACAGGCTCACTTCGCATG

1744 SEQ ID NO: 214 -17 -24.8 69.8 -6.8 -0.9 -4.8 ACCCATTTGCCAGAGGCTCC

2770 SEQ ID NO: 215 -17 -30.5 82 -11.4 -2.1 -7.5 GTGGTTCAGTGAAGATAAAG

2985 SEQ ID NO: 216 -17 -18.8 58.8 -1.3 0 -8 AGTGGTTCAGTGAAGATAAA

2986 SEQ ID NO: 217 -17 -18.8 58.8 -1.3 0 -7.5 AGTTTATTTTTTGGGGAAAA

3079 SEQ ID NO: 218 -17 -17.7 55.7 0 -0.4 -3.9 CTTCTTTCCTCTTGGAGGCA

1189 SEQ ID NO: 219 -16.9 -26.7 77.9 -8 -1.8 -8.4 CTGCTTCTTTCCTCTTGGAG

1192 SEQ ID NO: 220 -16.9 -25.7 75.9 -7.6 -1.1 -5.8 CACACACCTCGCCCTCGCCC

1522 SEQ ID NO: 221 -16.9 -34.5 84.8 -17 -0.3 -2.7 GCTCACTTCGCATGTAGATA

1738 SEQ ID NO: 222 -16.9 -23.9 70.1 -7 0 -4.8 TCGCCTTCATTGTTGGAGTC

2023 SEQ ID NO: 223 -16.9 -25.9 75.4 -8.5 -0.2 -4.2 TGAGTGGTTCAGTGAAGATA

2988 SEQ ID NO: 224 -16.9 -20.8 64.4 -3.4 -0.1 -8 CAGAGTGAGTGGTTCAGTGA

2993 SEQ ID NO: 225 -16.9 -23.7 72.7 -6.8 0 -5.5 GCCCTGTTGTGCTTGTATAT

3412 SEQ ID NO: 226 -16.9 -26.6 76.6 -9.7 0 -3.6 ATCCGGTTCAGCAGTCTTGG

1112 SEQ ID NO: 227 -16.8 -27.1 77.9 -10.3 0 -6.6 TGCTTCTTTCCTCTTGGAGG

1191 SEQ ID NO: 228 -16.8 -26 76.6 -7.6 -1.6 -6.9 CAACATGAAGGCCATCAGCA

2162 SEQ ID NO: 229 -16.8 -24.1 67.5 -5.8 -1.4 -9.2 GAGTGGTTCAGTGAAGATAA

2987 SEQ ID NO:230 -16.8 -20.1 62.2 -2.8 0 -8 CATCCATGACAACTATGATT

679 SEQ ID NO: 231 -16.7 -20.1 59.8 -2.9 -0.1 -5.5 GATAATTTTCAAGGTGCCAT

1653 SEQ ID NO: 232 -16.7 -21.2 62.8 -4.5 0 -6.2 CTGTTTCCTCTAGCATTCCT

2254 SEQ ID NO: 233 -16.7 -26.5 77.4 -9.8 0 -4.1 GACAGTTGTTCTTATTTTTA

2551 SEQ ID NO: 234 -16.7 -19.3 61.7 -2.6 0 -3.6 TCCGCTTGTGAGATTCTCCA

2576 SEQ ID NO: 235 -16.7 -26.9 75.8 -9.5 -0.4 -7.7 GTGAGTGGTTCAGTGAAGAT

2989 SEQ ID NO: 236 -16.7 -22.3 68.5 -4.9 -0.5 -8 AGTGAGTGGTTCAGTGAAGA

2990 SEQ ID NO: 237 -16.7 -22.3 68.8 -4.9 -0.5 -8 CCTTTACACAGAGTGAGTGG

3001 SEQ ID NO: 238 -16.7 -23.4 69.3 -5.6 -1 -5.6 GTCCTTCAAGTAGCCCTGAA

1560 SEQ ID NO:239 -16.6 -26.5 74.6 -9.4 -0.1 -3.4 AACAGGCTCACTTCGCATGT

1743 SEQ ID NO: 240 -16.6 -25.3 72 -6.8 -1.9 -6.4 ATTCAGGGTGCAATGTGATG

1978 SEQ ID NO: 241 -16.6 -22.4 66.5 -5.8 0 -5.4 TACACAGAGTGAGTGGTTCA

2997 SEQ ID NO: 242 -16.6 -22.7 69.3 -5 -1 -5.9 CCCTGTTGTGCTTGTATATA

3411 SEQ ID NO: 243 -16.6 -24.5 71.5 -7.9 0 -3.6 AAGCCCTGTTGTGCTTGTAT

3414 SEQ ID NO: 244 -16.6 -26.2 75 -8.3 -1.2 -4.8

94 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

Dsition oligo binding ation Duplex ture oligo oligo TGACTGCATGGAGAGGTCGC

177 SEQ ID NO: 245 -16.5 -26 74.1 -8.4 -1 -5.6 GCCCTCGCCCTCGGCAGCCA

1512 SEQ ID NO: 246 ^' -16.5 -38 92.9 -19.3 -2.2 -8.5 GATAGCTTTTTTGACATCCT

1896 SEQ ID NO: 247 -16.5 -22.3 66.7 -5.8 0 -4.6 CTTTACACAGAGTGAGTGGT

3000 SEQ ID NO: 248 -16.5 -22.6 68.8 -5.6 -0.1 -5.5 GCTGCTTTAAATGTACAAAT

3362 SEQ ID NO: 249 -16.5 -18.3 56.1 -1.8 0 -6.8 ACGCACGTACTGTCGGAAGT

63 SEQ ID NO: 250 -16.4 -25.2 69.6 -7.7 -1 -7.5 ACTTATTTTCTACACCCTCT

643 SEQ ID NO: 251 -16.4 -23.5 69.2 -7.1 0 -0.7 TGACAGCCCAGGGCTGCTCT

1352 SEQ ID NO: 252 -16.4 -31.1 85 -9.7 -4.7 -17.6 GTCGATAATTTTCAAGGTGC

1656 SEQ ID NO: 253 -16.4 -20.9 62.8 -4.5 0 -5 GAGCAACAGGCTCACTTCGC

1747 SEQ ID NO: 254 -16.4 -26.5 74.7 -6.8 -3.3 -9.3 GGAGTCAGAAGGCCATTGTC

2009 SEQ ID NO: 255 -16.4 -25.4 74.5 -8.5 0 -7.7 GCCTTCATTGTTGGAGTCAG

2021 SEQ ID NO: 256 -16.4 -25.4 75.3 -8.5 -0.2 -4.7 TTTACACAGAGTGAGTGGTT

2999 SEQ ID NO: 257 -16.4 -21.8 67.1 -4.3 -1 -5.6 AGCCATTCATAGGGTTGGTC

356 SEQ ID NO: 258 -16.3 -25.9 76.5 -9 -0.3 -5.2 TTTTCCGGTCGATAATTTTC

1663 SEQ ID NO: 259 -16.3 -21.4 63 -5.1 0 -6.6 CTTGTGCCAGCTTAAATATG

1687 SEQ ID NO: 260 -16.3 -21.5 63.2 -5.2 0 -4.5 ACAGGCTCACTTCGCATGTA

1742 SEQ ID NO: 261 -16.3 -25.7 73.8 -7.8 -1.6 -5.8 AGGACAGTTGTTCTTATTTT

2553 SEQ ID NO: 262 -16.3 -20.7 65 -4.4 0 -4.5 GCTACCAAGTAGTGTTATTA

3454 SEQ ID NO: 263 -16.3 -21.5 65.5 -4.2 -0.9 -5.2 TCCATGACAACTATGATTTT

677 SEQ ID NO: 264 -16.2 -19.6 59.3 -2.9 -0.1 -5.5 CTTGGGCTTCCGTCTGTTGG

783 SEQ ID NO: 265 -16.2 -28.4 80 -11 -1.1 -4.8 CACTATGTTTCGGTGAGTGA

876 SEQ ID NO: 266 -16.2 -22.9 68.1 -5.9 -0.6 -4.4 CTTTCCTCTTGGAGGCAAAG

1186 SEQ ID NO: 267 -16.2 -23.9 69.2 -5 -2.7 -9.1 GACAGCCCAGGGCTGCTCTG

1351 SEQ ID NO: 268 -16.2 -31.1 85 -10.1 -4.5 -17.4 AACTGACAGCCCAGGGCTGC

1355 SEQ ID NO: 269 -16.2 -29.3 79.3 -8.3 -4.5 -17.4 CTCGGCAGCCATGTAATTCA

1503 SEQ ID NO: 270 -16.2 -25.7 71.9 -8.9 0 -8.5 ATAATTTTCAAGGTGCCATT

1652 SEQ ID NO: 271 -16.2 -20.7 61.9 -4.5 0 -6.2 CCGGTCGATAATTTTCAAGG

1659 SEQ ID NO: 272 -16.2 -21.9 62.5 -5.7 0 -5.4 TTGACCTGTTCAAATGGTTT

1955 SEQ ID NO: 273 -16.2 -21.4 63.6 -4.3 -0.8 -5.1 ATGCCTTTGACCTGTTCAAA

1961 SEQ ID NO: 274 -16.2 -23.6 67.3 -5.8 -1.6 -6.6 TGCAATGTGATGCCTTTGAC

1970 SEQ ID NO: 275 -16.2 -23.3 67.2 -5.7 -1.3 -5

95 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture Oligo oligo GTCCGCTTGTGAGATTCTCC

2577 SEQ ID NO: 276 -16.2 -27.4 78.3 -10.5 -0.4 -7.7 AGCTGCTTTAAATGTACAAA

3363 SEQ ID NO: 277 -16.2 -18.3 56.3 -2.1 0 -6.8 CAGCTGCTTTAAATGTACAA

3364 SEQ ID NO: 278 -16.2 -19.7 59.4 -3.5 0 -7.2 GGCTTGCATTGTCCTGTGTT

3 SEQ ID NO: 279 -16.1 -27.6 80.2 -11.5 0 -5.1 ATCCATGACAACTATGATTT

678 SEQ ID NO: 280 -16.1 -19.5 59 -2.9 -0.1 -5.5 CTGTTGGCTCTTCCCAGGTC

770 SEQ ID NO: 281 -16.1 -29.4 84.7 -12.8 -0.2 -4.4 CAGCCATGTAATTCATTTCT

1498 SEQ ID NO: 282 -16.1 -22.1 65.7 -6 0 -4.3 GCCCTCGGCAGCCATGTAAT

1506 SEQ ID NO: 283 -16.1 -30.3 79.7 -12.5 -1.7 -8.5 TTGTTGGAGTCAGAAGGCCA

2014 SEQ ID NO: 284 -16.1 -25.1 73 -8.5 0 -7.7 TTTTCGCCTTCATTGTTGGA

2026 SEQ ID NO: 285 -16.1 -24.6 71.1 -8.5 0 -3.5 AACATGAAGGCCATCAGCAG

2161 SEQ ID NO: 286 -16.1 -23.4 66.7 -5.8 -1.4 -9.7 TTAACAACATGAAGGCCATC

2166 SEQ ID NO: 287 -16.1 -20.2 59.5 -3.6 0 -7.7 CCCCACACCTCTGGCCTCGT

721 SEQ ID NO: 288 -16 -34.3 87.1 -18.3 0 -7.2 ATATTTTCAATCTTTTCAGG

1721 SEQ ID NO: 289 -16 -18.3 58.4 -2.3 0 -1.8 AGCTTTTTTGACATCCTTAT

1893 SEQ ID NO: 290 -16 -21.8 65.7 -5.8 0 -4.3 ATAGCTTTTTTGACATCCTT

1895 SEQ ID NO: 291 -16 -21.8 65.7 -5.8 0 -4.6 GTCAGAAGGCCATTGTCGAT

2006 SEQ ID NO: 292 -16 -25 71.4 -8.5 0 -7.7 AGTCAGAAGGCCATTGTCGA

2007 SEQ ID NO: 293 -16 -25 71.7 -8.5 0 -7.7 GAGTCAGAAGGCCATTGTCG

2008 SEQ ID NO: 294 -16 -25 71.7 -8.5 0 -7.7 TGGAGTCAGAAGGCCATTGT

2010 SEQ ID NO: 295 -16 -25 72.6 -8.5 0 -7.7 GTTGGAGTCAGAAGGCCATT

2012 SEQ ID NO: 296 -16 -25.1 73.1 -8.5 -0.2 -8 TGTTGGAGTCAGAAGGCCAT

2013 SEQ ID NO: 297 -16 -25 72.6 -8.5 -0.2 -7.7 TTTCGCCTTCATTGTTGGAG

2025 SEQ ID NO: 298 -16 -24.5 71 -8.5 0 -3.3 GAGCACCCATTTGCCAGAGG

2774 SEQ ID NO: 299 -16 -28.5 77.6 -11.4 -1 -4.4 GAGCATTCTGCCATGAAAGA

2812 SEQ ID NO: 300 -16 -22.8 65.8 -5.2 -1.5 -7.1 TGGTTCAGTGAAGATAAAGT

2984 SEQ ID NO: 301 -16 -18.8 58.8 -2.3 0 -8 TTACACAGAGTGAGTGGTTC

2998 SEQ ID NO: 302 -16 -22.1 68.4 -5 -1 -5.6 GCCTTTACACAGAGTGAGTG

3002 SEQ ID NO: 303 -16 -24 71 -7.1 -0.8 -5.5 AATTCTTTAGTGCAAGCCCT

3427 SEQ ID NO: 304 -16 -24.3 69.7 -7.6 -0.4 -5.4 AGTACGCACGTACTGTCGGA

66 SEQ ID NO: 305 -15.9 -25.6 71.3 -7.7 -1.6 -11.8 GTCGGAAGAGTACGCACGTA

74 SEQ ID NO: 306 -15.9 -24.4 68.3 -7.7 -0.6 -7.9

96 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular ssition oligo binding ation Duplex ture oligo oligo GGGGTTTGGGTCTCGTGGCG

145 SEQ ID NO: 307 -15.9 -30.1 83.3 -14.2 0 -4.2 CTTATTTTCTACACCCTCTA

642 SEQ ID NO: 308 -15.9 -23 68 -7.1 0 -0.7 GGGTCCTTCAAGTAGCCCTG

1562 SEQ ID NO: 309 -15.9 -29 81.1 -12.2 -0.8 -5.4 CTTTGACCTGTTCAAATGGT

1957 SEQ ID NO: 310 -15.9 -22.2 65.2 -4.3 -2 -7.4 AATTCAGGGTGCAATGTGAT

1979 SEQ ID NO: 311 -15.9 -21.7 64.4 -5.8 0 -5.4 ATTGTTGGAGTCAGAAGGCC

2015 SEQ ID NO: 312 -15.9 -24.4 71.8 -8.5 0 -6.4 GCACCCATTTGCCAGAGGCT

2772 SEQ ID NO: 313 -15.9 -30.6 82.1 -12.6 -2.1 -7.5 AGAGCATTCTGCCATGAAAG

2813 SEQ ID NO: 314 -15.9 -22.2 64.7 -4.7 -1.5 -7.1 GTACGCACGTACTGTCGGAA

65 SEQ ID NO: 315 -15.8 -24.9 68.8 -7.7 -1 -10.3 CTCTGCTTCTTTCCTCTTGG

1194 SEQ ID NO: 316 -15.8 -26.4 78.1 -10.6 0 -3.6 CGAGGATAGCTTTTTTGACA

1900 SEQ ID NO: 317 -15.8 -21.6 64 -5.8 0 -4.6 TGCCTTTGACCTGTTCAAAT

1960 SEQ ID NO: 318 -15.8 -23.6 67.3 -5.8 -2 -7.8 GTATCCCCTTTACAATTTTT

2345 SEQ ID NO: 319 -15.8 -22.7 66.1 -6.9 0 -2.6 CCATTTGCCAGAGGCTCCTT

2768 SEQ ID NO: 320 -15.8 -29.3 80.3 -11.4 -2.1 -7.5 CAAGCCCTGTTGTGCTTGTA

3415 SEQ ID NO: 321 -15.8 -26.9 76.1 -8.3 -2.8 -8 TCACTATGTTTCGGTGAGTG

877 SEQ ID NO: 322 -15.7 -22.7 68.3 -5.9 -1 -5 GGCTCGACTGTACTTTGTGG

1264 SEQ ID NO: 323 -15.7 -25.4 73.5 -9.7 0 -4.8 AATATGTGCTTTTTCCGGTC

1673 SEQ ID NO: 324 -15.7 -23.3 68.2 -7.6 0 -6.6 CACTTCGCATGTAGATATTT

1735 SEQ ID NO: 325 -15.7 -21 63.1 -5.3 0 -4.8 TAGCTTTTTTGACATCCTTA

1894 SEQ ID NO: 326 -15.7 -21.5 65.2 -5.8 0 -4.6 CACCCATTTGCCAGAGGCTC

2771 SEQ ID NO: 327 -15.7 -29.2 79.6 -11.4 -2.1 -7.5 AGCACCCATTTGCCAGAGGC

2773 SEQ ID NO: 328 -15.7 -29.7 80.6 -12.6 -1.3 -6.7 ACTCAGGTCTATTTTGAGCA

472 SEQ ID NO: 329 -15.6 -23 70 -5.9 -1.4 -5.2 CTTCCGCCCAGGCTCGACTG

1274 SEQ ID NO: 330 -15.6 -31.5 81.5 -15.4 -0.1 -6.7 ACAGCCCAGGGCTGCTCTGA

1350 SEQ ID NO: 331 -15.6 -31.1 85 -10.7 -4.5 -17.4 CTGCATGGAGAGGTCGCATG

174 SEQ ID NO: 332 -15.5 -25.9 73.3 -8.6 -1.8 -6.5 CTCAGGTCTATTTTGAGCAA

471 SEQ ID NO: 333 -15.5 -22.1 67 -5.9 -0.5 -4.3 GCTCACTATGTTTCGGTGAG

879 SEQ ID NO: 334 -15.5 -24.2 71.5 -5.9 -2.8 -8.1 CTTTTCAGGGGCTATGTATT

1710 SEQ ID NO: 335 -15.5 -23.3 70 -7.8 0 -3.7 TCGAGGATAGCTTTTTTGAC

1901 SEQ ID NO: 336 -15.5 -21.3 64.2 -5.8 0 -4.6 TTCAAAACCCCAAGGTGACA

3519 SEQ ID NO: 337 -15.5 -23.2 64.1 -6.3 -1.3 -4.4

97 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

>sition oligo binding ation Duplex ture oligo oligo ATTGCACGGCATCGGGGCCC

1455 SEQ ID NO: 338 -15.4 -31.9 81.7 -14.6 -1.7 -11.5 TCGGCAGCCATGTAATTCAT

1502 SEQ ID NO: 339 -15.4 -24.8 70 -8.9 0 -8.3 GATATTTTCAATCTTTTCAG

1722 SEQ ID NO: 340 -15.4 -17.7 57.1 -2.3 0 -2.8 TTCGAGGATAGCTTTTTTGA

1902 SEQ ID NO: 341 -15.4 -21.2 64 -5.8 0 -4.8 AATTTTTAAGGCTCATTTTG

2332 SEQ ID NO: 342 -15.4 -18 56.8 -2.6 0 -4.3 CTTTACAATTTTTAAGGCTC

2338 SEQ ID NO: 343 -15.4 -18.7 58.4 -3.3 0 -3.7 CGCTTGTGAGATTCTCCAGC

2574 SEQ ID NO: 344 -15.4 -26.3 75.2 -10 -0.7 -8.4 CTTTCTTGAAATGCTTGTCT

2916 SEQ ID NO: 345 -15.4 -21 63.8 -4.9 -0.5 -5.2 CTGCCGTAGGCATCCATGAC

689 SEQ ID NO: 346 -15.3 -28 76.3 -8.2 -4.5 -13.4 CTCACTATGTTTCGGTGAGT

878 SEQ ID NO: 347 -15.3 -23.6 70.5 -5.9 -2.4 -7.3 GGACTCTTCCGCCCAGGCTC

1279 SEQ ID NO: 348 -15.3 -32.3 86.6 -15.7 -1.1 -9.7 AAAACTGACAGCCCAGGGCT

1357 SEQ ID NO: 349 -15.3 -26.1 70.7 -8.3 -2.2 -12.8 CGCCCTCGCCCTCGGCAGCC

1513 SEQ ID NO: 350 -15.3 -38.1 91.1 -20.6 -2.2 -7.4 TGACCTGTTCAAATGGTTTC

1954 SEQ ID NO: 351 -15.3 -21.7 64.7 -5.6 -0.6 -4.3 TTTGACCTGTTCAAATGGTT

1956 SEQ ID NO: 352 -15.3 -21.4 63.6 -4.3 -1.8 -7.4 ACAGCTGCTTTAAATGTACA

3365 SEQ ID NO: 353 -15.3 -20.6 61.9 -4.6 0 -8.9 CCAGAGAGAGTTCAGCTTTG

586 SEQ ID NO: 354 -15.2 -23.8 71.1 -8.6 0.4 -4.5 CCGGTTCAGCAGTCTTGGAA

1110 SEQ ID NO: 355 -15.2 -26.6 75 -11.4 0 -5.4 CTTTTTCCGGTCGATAATTT

1665 SEQ ID NO: 356 -15.2 -21.9 63.5 -6.7 0 -6.6 AGTATCCCCTTTACAATTTT

2346 SEQ ID NO: 357 -15.2 -22.6 65.9 -6.9 -0.1 -3.3 GCTTCTTTCCTCTTGGAGGC

1190 SEQ ID NO: 358 -15.1 -27.8 81.5 -10.9 -1.8 -8.4 ACACACACCTCGCCCTCGCC

1523 SEQ ID NO: 359 -15.1 -32.7 82.3 -17 -0.3 -2.7 GCTTTTTTGACATCCTTATT

1892 SEQ ID NO: 360 -15.1 -21.9 65.9 -6.8 0 -2.8 GGGTGCAATGTGATGCCTTT

1973 SEQ ID NO: 361 -15.1 -26.1 73.9 -9.6 -1.3 -6 CCCTTTACAATTTTTAAGGC

2340 SEQ ID NO: 362 -15.1 -21.4 62.6 -5.4 -0.7 -4.8 CAGGACAGTTGTTCTTATTT

2554 SEQ ID NO: 363 -15.1 -21.3 66 -6.2 0 -4.7 ACTGCATGGAGAGGTCGCAT

175 SEQ ID NO: 364 -15 -26.1 74 -10.4 -0.4 -5.1 CCGTAGGCATCCATGACAAC

686 SEQ ID NO: 365 -15 -25.5 69.9 -9.7 -0.6 -5.7 GCTTGGGCTTCCGTCTGTTG

784 SEQ ID NO: 366 -15 -29 81.8 -12.8 -1.1 -5 ATCGCTTCAGCGTGGTGTTT

1156 SEQ ID NO: 367 -15 -26.7 76.3 -9.8 -1.9 -9.9 AGCCATGTAATTCATTTCTT

1497 SEQ ID NO: 368 -15 -21.5 64.9 -6 -0.2 -4.3

98 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

->sition oligo binding ation Duplex ture oligo oligo CGGCAGCCATGTAATTCATT

1501 SEQ ID NO: 369 -15 -24.5 68.8 -8.9 -0.2 -8.3 TAATTTTCAAGGTGCCATTT

1651 SEQ ID NO: 370 -15 -20.8 62.2 -5.8 0 -6.2 GAGGATAGCTTTTTTGACAT

1899 SEQ ID NO: 371 -15 -20.8 63.6 -5.8 0 -4.6 CCTTTGACCTGTTCAAATGG

1958 SEQ ID NO: 372 -15 -23 65.7 -6 -2 -6.3 GTGTGTATTACCATAAACAT

2308 SEQ ID NO: 373 -15 -19.2 58.7 -4.2 3 -3.8 AGTGTGTATTACCATAAACA

2309 SEQ ID NO: 374 -15 -19.2 58.9 -4.2 3.2 -3.8 ATTTTGGAAAGTGTGTATTA

2318 SEQ ID NO: 375 -15 -17.8 56.8 -2.8 0 -2.4 CTGATGAGCACCCATTTGCC

2779 SEQ ID NO: 376 -15 -27.5 75 -11.4 -1 -5.9 GTTTATTTTTTGGGGAAAAA

3078 SEQ ID NO: 377 -15 -17 53.8 -0.6 -1.1 -4.6 TACGCACGTACTGTCGGAAG

64 SEQ ID NO: 378 -14.9 -23.7 66.1 -7.7 -1 -7.5 AATACACCAAGGGCTCGTCG

247 SEQ ID NO: 379 -14.9 -24.8 68 -9.9 0 -4.5 AAAACCAGAGAGAGTTCAGC

590 SEQ ID NO: 380 -14.9 -20.8 62.3 -5.3 -0.3 -3.4 GCCCAGGGCTGCTCTGAGGA

1347 SEQ ID NO: 381 -14.9 -32 87.4 -14.6 -1.9 -12.9 TTTTTCCGGTCGATAATTTT

1664 SEQ ID NO: 382 -14.9 -21.1 62 -6.2 0 -6 AGATATTTTCAATCTTTTCA

1723 SEQ ID NO: 383 -14.9 -17.7 57.1 -2.3 -0.2 -3.6 GCAATGTGATGCCTTTGACC

1969 SEQ ID NO: 384 -14.9 -25.3 70.9 -9.6 -0.6 -4 CCTTTACAATTTTTAAGGCT

2339 SEQ ID NO: 385 -14.9 -20.3 60.9 -4.9 -0.2 -3.9 ACAGTTGTTCTTATTTTTAA

2550 SEQ ID NO: 386 -14.9 -18 58.1 -3.1 0 -2.6 GATGAGCACCCATTTGCCAG

2777 SEQ ID NO: 387 -14.9 -27.3 74.6 -11.4 -0.9 -5.8 GGTCGGAAGAGTACGCACGT

75 SEQ ID NO: 388 -14.8 -25.9 71.3 -10.2 -0.7 -6.2 GGGTTTGGGTCTCGTGGCGT

144 SEQ ID NO: 389 -14.8 -30.1 84.4 -15.3 0 -4.2 CGCTCACTATGTTTCGGTGA

880 SEQ ID NO: 390 -14.8 -25 71.2 -9.1 -1 -5 TAAAACTGACAGCCCAGGGC

1358 SEQ ID NO: 391 -14.8 -24.9 68.4 -8.3 -1.4 -11.3 CAGGCTCACTTCGCATGTAG

1741 SEQ ID NO: 392 -14.8 -25.5 73.5 -10 -0.5 -4.8 AGGATAGCTTTTTTGACATC

1898 SEQ ID NO: 393 -14.8 -20.6 63.7 -5.8 0 -4.3 TTGGAGTCAGAAGGCCATTG

2011 SEQ ID NO: 394 -14.8 -23.9 69.5 -8.5 -0.2 -8 TAACAACATGAAGGCCATCA

2165 SEQ ID NO: 395 -14.8 -20.8 60.4 -5.2 0 -9.4 TAGTATCCCCTTTACAATTT

2347 SEQ ID NO: 396 -14.8 -22.2 65 -6.9 -0.1 -3.3 GCTTGTGAGATTCTCCAGCC

2573 SEQ ID NO: 397 -14.8 -27.5 79.2 -11.9 -0.6 -8.2 TGAGCACCCATTTGCCAGAG

2775 SEQ ID NO: 398 -14.8 -27.3 74.9 -11.4 -1 -4.4 ATGAGCACCCATTTGCCAGA

2776 SEQ ID NO: 399 -14.8 -27.3 74.6 -11.4 -1 -4.6

99 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TGATGAGCACCCATTTGCCA 2778 SEQ ID NO:400 -14.8 -27.3 74.1 -11.4 -1 -5.9

GTCCAAGAGCATTCTGCCAT 2818 SEQ ID NO: 401 -14.8 -26.6 75.2 -10.2 -1.5 -5.1

CGCACGTACTGTCGGAAGTC 62 SEQ ID NO: 402 -14.7 -25.4 70.6 -10.2 -0.2 -6

AAATACACCAAGGGCTCGTC 248 SEQ ID NO: 403 -14.7 -23.3 65.8 -8.6 0 -4.5

GGCCATTATTTGACACCTGT 313 SEQ ID NO:404 -14.7 -25.5 72.1 -10.8 0 -7

CCTCGTTCCACCAGTTCACT 707 SEQ ID NO: 405 -14.7 -28.9 79.6 -14.2 0 -3

GCAGCCATGTAATTCATTTC 1499 SEQ ID NO: 406 -14.7 -23 68 -7.8 -0.2 -5.2

CTGAGCAACAGGCTCACTTC 1749 SEQ ID NO: 407 -14.7 -24.8 72.3 -6 -4.1 -9.5

ATAGTATCCCCTTTACAATT 2348 SEQ ID NO:408 -14.7 -22.1 64.7 -6.9 -0.1 -3.3

ACAGAGTGAGTGGTTCAGTG 2994 SEQ ID NO:409 -14.7 -23.3 71.9 -7.9 -0.5 -5

TCAGGGGTTTGGGTCTCGTG 148 SEQ ID NO:410 -14.6 -27.4 79.9 -12.8 0 -3

TCACTGCCGTAGGCATCCAT 692 SEQ ID NO: 411 -14.6 -28.5 77.9 -9.4 -4.5 -9.2

CATCGCTTCAGCGTGGTGTT 1157 SEQ ID NO: 412 -14.6 -27.3 77 -10.8 -1.9 -9.9

AAATATGTGCTTTTTCCGGT 1674 SEQ ID NO:413 -14.6 -22.2 64.6 -7.6 0 -6.6

TCTTTTCAGGGGCTATGTAT 1711 SEQ ID NO:414 -14.6 -23.6 71.4 -9 0 -4.4

TATTTTCAATCTTTTCAGGG 1720 SEQ ID NO:415 -14.6 -19.5 61.1 -4.9 0 -1.8

CATTGTTGGAGTCAGAAGGC 2016 SEQ ID NO: 416 -14.6 -23.1 69.1 -8.5 0 -4.7

ACAATTCTTTAGTGCAAGCC 3429 SEQ ID NO: 417 -14.6 -22.3 65.9 -7 -0.4 -5.4

TATGAAGTTAGGCTACCAAG 3465 SEQ ID NO:418 -14.6 -20.4 61.4 -5.2 -0.3 -3.7

TCGCCCTCGGCAGCCATGTA 1508 SEQ ID NO:419 -14.5 -32.2 83.5 -15.5 -2.2 -8.5

GTAGATATTTTCAATCTTTT

1725 SEQ ID NO:420 -14.5 -17.5 56.9 -2.3 -0.4 -3.7 CTCTAGCATTCCTATGAGAA

2247 SEQ ID NO:421 -14.5 -22 65.6 -6.8 -0.4 -3.9

GCTTGCCTGAGAGTTTATTT 3090 SEQ ID NO:422 -14.5 -24 71.3 -9.5 0 -3.1

ATACACCAAGGGCTCGTCGC 246 SEQ ID NO: 423 -14.4 -27.3 74.1 -12.4 -0.1 -4.5

AGGGCCATTATTTGACACCT 315 SEQ ID NO:424 -14.4 -25.5 71.7 -10.6 0 -7.6

CACTCAGGTCTATTTTGAGC 473 SEQ ID NO: 425 -14.4 -23 70 -7.1 -1.4 -5.2

GACTCTTCCGCCCAGGCTCG 1278 SEQ ID NO:426 -14.4 -31.9 83.4 -17 -0.1 -7.2

TGTAGATATTTTCAATCTTT

1726 SEQ ID NO:427 -14.4 -17.4 56.5 -2.3 -0.4 -3.7 CTCTTTTGGGCCCAGGAACA

1838 SEQ ID NO:428 -14.4 -27.4 75.4 -10.9 0 -12.4

TAATTCAGGGTGCAATGTGA

1980 SEQ ID NO:429 -14.4 -21.4 63.9 -7 0 -5.4

CCATTGTCGATAGAAAATAA

1997 SEQ ID NO:430 -14.4 -17 52.5 -2.6 2.3 -5

100 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo GAGTCCAAGAGCATTCTGCC

2820 SEQ ID NO: 431 -14.4 -26.5 75.8 -10.5 -1.5 -5.3 TTTCTTGAAATGCTTGTCTT

2915 SEQ ID NO: 432 -14.4 -20.2 62.2 -5.2 -0.3 -5.2 ACCAAGTAGTGTTATTACAA

3451 SEQ ID NO: 433 -14.4 -19.3 59.5 -4.2 -0.5 -4.9 GTCGGAAGTCAACCAGCTCT

52 SEQ ID NO: 434 -14.3 -26 73.6 -11.2 -0.2 -4.5 TTATTTTCTACACCCTCTAA

641 SEQ ID NO: 435 -14.3 -21.4 63.9 -7.1 0 -1 GTTCACTGCCGTAGGCATCC

694 SEQ ID NO: 436 -14.3 -29.1 80.8 -10.3 -4.5 -10.3 GCCTCGTTCCACCAGTTCAC

708 SEQ ID NO: 437 -14.3 -29.8 82 -15.5 0 -3 CTATGTTTCGGTGAGTGACC

874 SEQ ID NO: 438 -14.3 -24.2 70.7 -9.1 -0.6 -3.5 AAATCCGATTTTAGCTCCAT

1023 SEQ ID NO: 439 -14.3 -22.2 63.5 -7.9 0 -6.4 CGCCCTCGGCAGCCATGTAA

1507 SEQ ID NO: 440 -14.3 -31.1 79.4 -14.6 -2.2 -8.5 GCTTTTTCCGGTCGATAATT

1666 SEQ ID NO: 441 -14.3 -23.6 67.1 -9.3 0 -6.6 ATGTAGATATTTTCAATCTT

1727 SEQ ID NO: 442 -14.3 -17.3 56.1 -2.3 -0.4 -3.7 TCTGTTTCCTCTAGCATTCC

2255 SEQ ID NO: 443 -14.3 -26 77.2 -11.7 0 -4.1 TATCCCCTTTACAATTTTTA

2344 SEQ ID NO: 444 -14.3 -21.2 62.5 -6.9 0 -2.6 TCCAGCCAGGACAGTTGTTC

2560 SEQ ID NO: 445 -14.3 -27.3 79 -12.1 -0.8 -5 CAGACCCCAAAACAGCTGCT

3376 SEQ ID NO: 446 -14.3 -26.4 70.4 -11.4 0 -8.9 ATTTTCTACACCCTCTAATA

639 SEQ ID NO: 447 -14.2 -21.3 63.5 -7.1 0 -1.6 TATTTTCTACACCCTCTAAT

640 SEQ ID NO: 448 -14.2 -21.3 63.5 -7.1 0 -1.7 CACTGCCGTAGGCATCCATG

691 SEQ ID NO: 449 -14.2 -28.1 76.1 -9.4 -4.5 -12.8 GACCATTGCTCCTTTGGGGT

858 SEQ ID NO: 450 -14.2 -28.6 79.8 -13.5 -0.7 -5.7 GGTGAGTGACCATTGCTCCT

865 SEQ ID NO: 451 -14.2 -27.8 78.8 -12.3 -1.2 -6 TCGCTCACTATGTTTCGGTG

881 SEQ ID NO: 452 -14.2 -24.8 71.5 -10.6 0.5 -4.1 ATTCTCTGTTGCTTTCACAA

912 SEQ ID NO: 453 -14.2 -22.2 67.4 -8 0 -3.6 TGGAAAGTGTGTATTACCAT

2314 SEQ ID NO: 454 -14.2 -20.4 61.4 -6.2 0 -3.8 AAAAGGATGGAGTCGGGGAA

2856 SEQ ID NO: 455 -14.2 -21.4 61.5 -7.2 0.6 -4.7 AAAAAGGATGGAGTCGGGGA

2857 SEQ ID NO: 456 -14.2 -21.4 61.5 -6.7 -0.2 -4.7 GGTTCAGTGAAGATAAAGTA

2983 SEQ ID NO: 457 -14.2 -18.5 58.3 -3.8 0 -8 CCTGAGAGTTTATTTTTTGG

3085 SEQ ID NO: 458 -14.2 -20.9 63.9 -6.7 0 -2.3 CCAAGTAGTGTTATTACAAT

3450 SEQ ID NO: 459 -14.2 -19.1 58.9 -4.2 -0.5 -5.7 TCGGAAGAGTACGCACGTAC

73 SEQ ID NO: 460 -14.1 -23.4 65.8 -7.7 -0.8 -11.1 CATCCGGTTCAGCAGTCTTG

1113 SEQ ID NO: 461 -14.1 -26.6 76.4 -12.5 0 -6.6 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GGTGCCATTTGGTAACCATT 1641 SEQ ID NO:462 -14.1 -25.5 71.8 -10.6 -0.6 -8.1

TCTCTTTTGGGCCCAGGAAC 1839 SEQ ID NO:463 -14.1 -27.1 76.1 -10.9 0 -12.4

CTCCAGCCAGGACAGTTGTT 2561 SEQ ID NO: 464 -14.1 -27.8 79.1 -12.6 -1 -5.2

CATTTGCCAGAGGCTCCTTA 2767 SEQ ID NO: 465 -14.1 -27 76.2 -11.4 -1.4 -6.8

CACAGAGTGAGTGGTTCAGT 2995 SEQ ID NO:466 -14.1 -24 73.3 -9.4 -0.1 -5.6

AGCCCTGTTGTGCTTGTATA 3413 SEQ ID NO: 467 -14.1 -26.6 77 -11.9 -0.3 -3.8

ATTCTTTAGTGCAAGCCCTG 3426 SEQ ID NO:468 -14.1 -25 71.9 -10.2 -0.4 -5.4

GGGCTTGCATTGTCCTGTGT 4 SEQ ID NO: 469 -14 -28.7 82.6 -14.7 0 -7.2

ATTAACTTATTTTCTACACC 647 SEQ ID NO:470 -14 -18.4 57.6 -4.4 0 -2.9

CAGCCCAGGGCTGCTCTGAG 1349 SEQ ID NO:471 -14 -30.9 84.8 -12.9 -3.6 -15.7

TTGCACGGCATCGGGGCCCC 1454 SEQ ID NO: 472 -14 -33.9 84.9 -16.7 -1.7 -14.5

TTTTCAAGGTGCCATTTGGT 1648 SEQ ID NO: 473 -14 -24.2 70.8 -10.2 0 -6.2

TTGTGCCAGCTTAAATATGT 1686 SEQ ID NO:474 -14 -21.8 64.4 -7.8 0 -4.5

GACCTGTTCAAATGGTTTCA 1953 SEQ ID NO:475 -14 -22.4 66 -7.6 -0.6 -4.3

CATTGTCGATAGAAAATAAT 1996 SEQ ID NO:476 -14 -15 49 -0.9 2.3 -4.5

CTTTTCGCCTTCATTGTTGG 2027 SEQ ID NO:477 -14 -24.9 71.7 -10.9 0 -3

TTGCCAGAGGCTCCTTATCT 2764 SEQ ID NO:478 -14 -27.5 78.5 -11.4 -2.1 -7.5

GTTCTGATGAGCACCCATTT 2782 SEQ ID NO:479 -14 -25.4 72.7 -11.4 0 -4.1

TTCTACACCCTCTAATAAGA 636 SEQ ID NO:480 -13.9 -21 62.3 -7.1 0 -2.6

GCATTACACACTCTACAACT 997 SEQ ID NO: 481 -13.9 -21.5 63.8 -7.6 0 -3.4

CTGCAGGCTTTCTCCGTGGA 1776 SEQ ID NO: 482 -13.9 -29 80.8 -15.1 0.6 -7.6

AGGGTGCAATGTGATGCCTT 1974 SEQ ID NO: 483 -13.9 -26 73.8 -11.2 -0.7 -6

GGAAAGTGTGTATTACCATA 2313 SEQ ID NO:484 -13.9 -20.1 60.9 -6.2 0 -3.6

ATCCCCTTTACAATTTTTAA 2343 SEQ ID NO:485 -13.9 -20.8 61 -6.9 0 -2.6

GAGTTGGATCTGCCCTCCCG 2734 SEQ ID NO:486 -13.9 -30.9 82.1 -17 0.2 -5

GACAATTCTTTAGTGCAAGC 3430 SEQ ID NO:487 -13.9 -20.9 63.4 -7 0 -5.4

ATTCAAAACCCCAAGGTGAC 3520 SEQ ID NO:488 -13.9 -22.5 63 -7.2 -1.3 -4.7

ACTGCCGTAGGCATCCATGA 690 SEQ ID NO: 489 -13.8 -28 76.3 -9.7 -4.5 -13.4

TCTCCTTGGAAAAATCCGAT

1034 SEQ ID NO: 490 -13.8 -21.5 61.1 -6.8 -0.7 -5.3 ATCTCCTTGGAAAAATCCGA

1035 SEQ ID NO:491 -13.8 -21.5 61.1 -6.8 -0.7 -5.3 AAACTGACAGCCCAGGGCTG

1356 SEQ ID NO : 492 -13.8 -26.8 72.8 -8.3 -4.3 -17.1

102 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCCAAGTCTCACCATATCTT 1920 SEQ ID NO:493 -13.8 -25.6 72.3 -11.8 0 -2.4

AAATTAACAACATGAAGGCC 2169 SEQ ID NO: 494 -13.8 -17.7 53.7 -3.9 0 -6.4

GTGTATTACCATAAACATGG

2306 SEQ ID NO: 495 -13.8 -19.2 58.2 -4.2 -1.1 -5.8 TGTGTATTACCATAAACATG

2307 SEQ ID NO: 496 -13.8 -18 55.7 -4.2 0.1 -4.7 CCCCAAGGTGACAAATTATT

3512 SEQ ID NO: 497 -13.8 -22.4 62.9 -8.6 0 -3.3

TTCATTGTTTTTGGAAATTT 3586 SEQ ID NO: 498 -13.8 -17.5 55.7 -3.7 0 -5.5

CGGTGAGTGACCATTGCTCC 866 SEQ ID NO:499 -13.7 -27.7 76.5 -12.3 -1.7 -6.2

AAAATCCGATTTTAGCTCCA 1024 SEQ ID NO: 500 -13.7 -21.5 61.6 -6.9 -0.7 -8.4

GGCGGCTCCTGTCACCATCA 1302 SEQ ID NO: 501 -13.7 -31.3 84.4 -17.1 -0.1 -6.2

TGGGTCCTTCAAGTAGCCCT 1563 SEQ ID NO: 502 -13.7 -29 81.1 -13.7 -1.5 -6.2

TAGATATTTTCAATCTTTTC 1724 SEQ ID NO: 503 -13.7 -16.7 55.1 -2.3 -0.4 -3.7

TGCCTGCAGGCTTTCTCCGT 1779 SEQ ID NO: 504 -13.7 -31 84.8 -12.8 -2.1 -17.2

TATAGTATCCCCTTTACAAT 2349 SEQ ID NO: 505 -13.7 -21.7 63.8 -7.5 -0.1 -3.3

AGGGACAGTAGCAGGGATTT 2610 SEQ ID NO:506 -13.7 -24.5 72.5 -10.8 0 -4.1

TCTGATGAGCACCCATTTGC 2780 SEQ ID NO: 507 -13.7 -25.9 73.1 -11.4 -0.6 -5.5

AAGAGCATTCTGCCATGAAA 2814 SEQ ID NO: 508 -13.7 -21.5 62.5 -6.2 -1.5 -7.1

TGAAAAAGGATGGAGTCGGG 2859 SEQ ID NO: 509 -13.7 -20.2 59.1 -6 -0.2 -4.7

GTAACTCTTTCTTGAAATGC 2922 SEQ ID NO: 510 -13.7 -19.2 59.5 -4.8 -0.5 -5

AGACCCCAAAACAGCTGCTT 3375 SEQ ID NO:511 -13.7 -25.8 69.7 -11.4 0 -8.9

GGGGCAGTCTTGAAGCCCTT 431 SEQ ID NO:512 -13.6 -29.4 81.5 -11.7 -4.1 -11.4

ATCGCTCACTATGTTTCGGT 882 SEQ ID NO: 513 -13.6 -24.8 71.6 -11.2 0 -3.1

GCTCTGCTTCTTTCCTCTTG 1195 SEQ ID NO: 514 -13.6 -27 80 -13.4 0 -2.9

TCCTGTCACCATCAGCCGGA 1296 SEQ ID NO: 515 -13.6 -30 80.7 -15.8 -0.2 -8.2

GCCATGTAATTCATTTCTTC 1496 SEQ ID NO: 516 -13.6 -21.9 66.2 -7.8 -0.2 -4.3

TTTCAAGGTGCCATTTGGTA 1647 SEQ ID NO: 517 -13.6 -23.8 69.8 -10.2 0 -6.2

AATTTTCAAGGTGCCATTTG 1650 SEQ ID NO: 518 -13.6 -21.1 62.7 -7.5 0 -6.2

TCACTTCGCATGTAGATATT 1736 SEQ ID NO: 519 -13.6 -21.3 64.2 -7.7 0 -4.8

TCTTTTGGGCCCAGGAACAT 1837 SEQ ID NO: 520 -13.6 -26.5 73.5 -10.9 0 -12.1

AGGCGGTGTTCTGTTTCCTC 2264 SEQ ID NO: 521 -13.6 -27.9 81.5 -14.3 0 -4

GTATTACCATAAACATGGTC 2304 SEQ ID NO: 522 -13.6 -19.6 59.6 -4.2 -1.8 -7.5

CCAGGACAGTTGTTCTTATT 2555 SEQ ID NO: 523 -13.6 -23.2 69.5 -9.6 0 -4.7

103 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TCCAAGAGCATTCTGCCATG 2817 SEQ ID NO: 524 -13.6 -25.4 71.6 -10.2 -1.5 -7.1

CGAGTCCAAGAGCATTCTGC 2821 SEQ ID NO: 525 -13.6 -25.3 72 -10.5 -1.1 -5.5

CAAAACCCCAAGGTGACAAA 3517 SEQ ID NO:526 -13.6 -21.3 59.1 -6.3 -1.3 -4.4

TTTTCTACACCCTCTAATAA 638 SEQ ID NO: 527 -13.5 -20.6 61.5 -7.1 0 -1.2

ACCCCACACCTCTGGCCTCG 722 SEQ ID NO: 528 -13.5 -33.3 84.4 -19.8 0 -7.2

TTCTCTGTTGCTTTCACAAA 911 SEQ ID NO: 529 -13.5 -21.5 65.2 -8 0 -3.6

TCGCTTCAGCGTGGTGTTTG 1155 SEQ ID NO: 530 -13.5 -26.7 76.2 -11.3 -1.9 -9.9

ATCCTTCCCAAGTCTCACCA 1926 SEQ ID NO: 531 -13.5 -28.3 78.1 -14.8 0 -2.3

TCCCTGGAGAAGTGAATCCC 3262 SEQ ID NO: 532 -13.5 -26.5 72.8 -13 0.1 -4.4

ATATGAAGTTAGGCTACCAA 3466 SEQ ID NO: 533 -13.5 -20.4 61.1 -6.3 -0.3 -3.7

GTTGGTCGGAAGAGTACGCA 78 SEQ ID NO: 534 -13.4 -25 71 -11.1 -0.2 -5.8

TACACCAAGGGCTCGTCGCT 245 SEQ ID NO: 535 -13.4 -28.2 76 -13.8 -0.9 -5.1

TCAGGTCTATTTTGAGCAAA 470 SEQ ID NO: 536 -13.4 -20.5 62.7 -7.1 0 -5.5

CCCACTCAGGTCTATTTTGA 475 SEQ ID NO: 537 -13.4 -25.2 72.9 -11.3 -0.1 -3.3

TTTCTACACCCTCTAATAAG 637 SEQ ID NO: 538 -13.4 -20.5 61.3 -7.1 0 -1.6

CCATGACAACTATGATTTTA 676 SEQ ID NO: 539 -13.4 -18.9 57.5 -5 -0.1 -5.5

TGTTGGCTCTTCCCAGGTCC 769 SEQ ID NO: 540 -13.4 -30.5 86.2 -16.6 -0.2 -3.6

GTGAGTGACCATTGCTCCTT 864 SEQ ID NO: 541 -13.4 -26.7 76.5 -12.3 -0.9 -3.8

TATTCTCTGTTGCTTTCACA 913 SEQ ID NO: 542 -13.4 -22.6 69.3 -9.2 0 -3.6

TTTTAGCTCCATGACACAGC 1015 SEQ ID NO: 543 -13.4 -24 70.2 -10.6 0.6 -4.8

CTCTTGGAGGCAAAGTCCAA 1181 SEQ ID NO: 544 -13.4 -24 68.6 -8.6 -2 -6.6

CCTGTCACCATCAGCCGGAC 1295 SEQ ID NO: 545 -13.4 -29.8 79.6 -15.8 -0.2 -8.2

ATTGTCGATAGAAAATAATT 1995 SEQ ID NO: 546 -13.4 -14.4 48 -0.9 2.5 -5.2

GCCATTGTCGATAGAAAATA 1998 SEQ ID NO: 547 -13.4 -19.5 57.9 -6.1 2.3 -5

AACGCTTCCTTCCCTACACT 2200 SEQ ID NO: 548 -13.4 -27.5 74.4 -14.1 0 -3.3

GTTCTGTTTCCTCTAGCATT 2257 SEQ ID NO: 549 -13.4 -24.9 75.6 -11.5 0 -4.1

TTTTGGAAAGTGTGTATTAC 2317 SEQ ID NO: 550 -13.4 -18 57.3 -4.6 0 -3

ATTTTTAAGGCTCATTTTGG 2331 SEQ ID NO: 551 -13.4 -19.9 61.4 -6.5 0 -4.3

TTATAGTATCCCCTTTACAA 2350 SEQ ID NO: 552 -13.4 -21.8 64.1 -8.4 0.7 -3.3

GGGACAGTAGCAGGGATTTA 2609 SEQ ID NO: 553 -13.4 -24.2 71.6 -10.8 0 -4.1

GGCCTTTACACAGAGTGAGT 3003 SEQ ID NO: 554 -13.4 -25.2 73.9 -10.9 -0.8 -7.7

104 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TTCACTGCCGTAGGCATCCA

693 SEQ ID NO: 555 -13.3 -28.6 78.4 -11 -4.3 -8.8 TCCTTGGAAAAATCCGATTT

1032 SEQ ID NO: 556 -13.3 -20.4 58.8 -7.1 0 -7 AGGTGCCATTTGGTAACCAT

1642 SEQ ID NO: 557 -13.3 -25.4 71.7 -10.6 -1.4 -8.8 TGTTCTGTTTCCTCTAGCAT

2258 SEQ ID NO: 558 -13.3 -24.8 75 -11.5 0 -4.1 CCCCTTTACAATTTTTAAGG

2341 SEQ ID NO: 559 -13.3 -21.6 62.3 -7.6 -0.5 -4.5 GAAAAAGGATGGAGTCGGGG

2858 SEQ ID NO: 560 -13.3 -21.4 61.5 -7.6 -0.2 -4.7 CCTGTTGTGCTTGTATATAA

3410 SEQ ID NO: 561 -13.3 -21.8 65.4 -8.5 0 -5.2 GCCATTATTTGACACCTGTA

312 SEQ ID NO: 562 -13.2 -24 68.9 -10.8 0 -3.6 TATGTTTCGGTGAGTGACCA

873 SEQ ID NO: 563 -13.2 -24 69.9 -9.1 -1.7 -4.3 AAAAATCCGATTTTAGCTCC

1025 SEQ ID NO: 564 -13.2 -20.1 58.7 -5.6 -1.2 -9.3 GCTCGACTGTACTTTGTGGA

1263 SEQ ID NO: 565 -13.2 -24.8 72.2 -11.6 0 -4.8 ACCTCGCCCTCGCCCTCGGC

1517 SEQ ID NO: 566 -13.2 -37.1 90 -22.7 -1.1 -5.8 CCTTCAAGTAGCCCTGAAAT

1558 SEQ ID NO: 567 -13.2 -24.2 67.6 -10.4 -0.3 -3.5 CAATGTGATGCCTTTGACCT

1968 SEQ ID NO: 568 -13.2 -24.4 68.7 -11.2 0 -3 CTTCATTGTTGGAGTCAGAA

2019 SEQ ID NO: 569 -13.2 -21.5 65.7 -8.3 0 -4.7 ACGCTTCCTTCCCTACACTT

2199 SEQ ID NO: 570 -13.2 -28.3 77.1 -15.1 0 -3.3 CTTGTGAGATTCTCCAGCCA

2572 SEQ ID NO: 571 -13.2 -26.4 75.8 -12.7 -0.1 -7.2 TTTGCCAGAGGCTCCTTATC

2765 SEQ ID NO: 572 -13.2 -26.7 76.9 -11.4 -2.1 -7.5 AAAGGATGGAGTCGGGGAAT

2855 SEQ ID NO: 573 -13.2 -22.1 63.4 -8.4 -0.2 -4.7 CAATTCTTTAGTGCAAGCCC

3428 SEQ ID NO: 574 -13.2 -24.1 69 -10.2 -0.4 -5.4 CCACTCAGGTCTATTTTGAG

474 SEQ ID NO: 575 -13.1 -23.2 69.4 -8.8 -1.2 -4.9 TTGGAAAAATCCGATTTTAG

1029 SEQ ID NO: 576 -13.1 -16.9 52.4 -2.8 -0.7 -8.8 GTGCCATTTGGTAACCATTT

1640 SEQ ID NO: 577 -13.1 -24.4 69.6 -10.6 -0.4 -6.2 TAAATATGTGCTTTTTCCGG

1675 SEQ ID NO: 578 -13.1 -20.7 61 -7.6 0 -6 TCCTTCCCAAGTCTCACCAT

1925 SEQ ID NO: 579 -13.1 -28.3 78.1 -15.2 0 -2.3 TGTATTACCATAAACATGGT

2305 SEQ ID NO: 580 -13.1 -19.2 58.2 -4.2 -1.9 -7.4 GGAACACTTCCCTCTAGTGC

2528 SEQ ID NO: 581 -13.1 -26.5 75.5 -11.9 -1.4 -6.2 AGTCCAAGAGCATTCTGCCA

2819 SEQ ID NO: 582 -13.1 -26.6 75.5 -11.9 -1.5 -5.1 CATTCAAAACCCCAAGGTGA

3521 SEQ ID NO: 583 -13.1 -23 63.6 -8.5 -1.3 -4.7 TCATTGTTTTTGGAAATTTT

3585 SEQ ID NO: 584 -13.1 -17.5 55.7 -4.4 0 -5.7 CGTACTGTCGGAAGTCAACC

58 SEQ ID NO: 585 -13 -24.1 67.8 -11.1 0 -4.5

105 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

AGAGTACGCACGTACTGTCG 68 SEQ ID NO: 586 -13 -24.4 69.1 -9 -2.1 -12.5

AGCATTACACACTCTACAAC 998 SEQ ID NO: 587 -13 -20.6 62.1 -7.6 0 -4.1

GCTTCAGCGTGGTGTTTGCT

1153 SEQ ID NO: 588 -13 -28.2 81.4 -14.5 -0.5 -5.9 CGCTTCAGCGTGGTGTTTGC

1154 SEQ ID NO: 589 -13 -28.1 78.9 -13.7 -1.3 -8.7 TATTACCATAAACATGGTCT

2303 SEQ ID NO: 590 -13 -19.3 58.6 -4.2 -2.1 -7.8

TCTCCAGCCAGGACAGTTGT 2562 SEQ ID NO:591 -13 -28.1 80.6 -14 -1 -5.2

TCTTTCTTGAAATGCTTGTC 2917 SEQ ID NO: 592 -13 -20.5 63.3 -6.8 -0.5 -5.2

GGTTTGGGTCTCGTGGCGTA 143 SEQ ID NO: 593 -12.9 -28.6 81.1 -15.7 0 -4.2

TGGGGCAGTCTTGAAGCCCT 432 SEQ ID NO: 594 -12.9 -29.3 80.9 -12.3 -4.1 -11.4

GTTCAGCAGTCTTGGAACCA 1107 SEQ ID NO: 595 -12.9 -25.5 74.3 -11.8 -0.6 -5.3

AATTGCACGGCATCGGGGCC 1456 SEQ ID NO: 596 -12.9 -29.2 76.2 -14.6 -1.7 -8

GCCAGCTTAAATATGTGCTT 1682 SEQ ID NO: 597 -12.9 -23.3 67.4 -9.7 -0.4 -4.5

ATAATTCAGGGTGCAATGTG 1981 SEQ ID NO:598 -12.9 -20.8 62.6 -7.9 0 -5.4

AAAATTAACAACATGAAGGC 2170 SEQ ID NO: 599 -12.9 -15 48.7 -2.1 0 -5.2

TTCTTGAAATGCTTGTCTTC 2914 SEQ ID NO: 600 -12.9 -20.5 63.3 -7.6 0 -3.6

AACAGCTGCTTTAAATGTAC 3366 SEQ ID NO:601 -12.9 -19.2 58.7 -5.6 0 -8.9

AAAACCCCAAGGTGACAAAT 3516 SEQ ID NO: 602 -12.9 -20.6 58 -6.3 -1.3 -4.4

TGTCGGAAGTCAACCAGCTC 53 SEQ ID NO: 603 -12.8 -25.1 71.5 -11.8 -0.2 -4.5

GCACGTACTGTCGGAAGTCA 61 SEQ ID NO: 604 -12.8 -25.3 71.7 -12 -0.2 -5.5

AAGGGCCATTATTTGACACC 316 SEQ ID NO:605 -12.8 -23.9 67.6 -10.6 0 -7.8

GGCTCCTGTCACCATCAGCC 1299 SEQ ID NO: 606 -12.8 -31.3 86.4 -16.9 -1.6 -4.8

ATTTGGCCCTTTCACACACA 1536 SEQ ID NO: 607 -12.8 -26.1 72.9 -13.3 0 -6.6

CCCAGGAACATAATGTCTCA 1828 SEQ ID NO: 608 -12.8 -23.3 66.4 -10.5 0 -4.2

CTTTTGGGCCCAGGAACATA 1836 SEQ ID NO:609 -12.8 -25.8 71.4 -10.9 0 -12.4

TTTATAGTATCCCCTTTACA 2351 SEQ ID NO: 610 -12.8 -22.6 66.7 -9.3 -0.1 -3.3

ATTTGCCAGAGGCTCCTTAT 2766 SEQ ID NO: 611 -12.8 -26.3 75 -11.4 -2.1 -7.5

TTCTGATGAGCACCCATTTG 2781 SEQ ID NO: 612 -12.8 -24.2 69.3 -11.4 0 -4.1

CTTGCCTGAGAGTTTATTTT 3089 SEQ ID NO: 613 -12.8 -22.3 67.2 -9.5 0 -3

ACAGACCCCAAAACAGCTGC 3377 SEQ ID NO: 614 -12.8 -25.7 69.2 -12.2 -0.1 -8.9

AAACCCCAAGGTGACAAATT 3515 SEQ ID NO: 615 -12.8 -21.4 60 -7.2 -1.3 -5.4

GGTATTAACTTATTTTCTAC 650 SEQ ID NO: 616 -12.7 -17.6 56.9 -4.4 -0.2 -2.9

106 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GTTGGCTCTTCCCAGGTCCT 768 SEQ ID NO: 617 -12.7 -31.4 88.6 -18.2 -0.2 -4.4

TCTCTGTTGCTTTCACAAAA 910 SEQ ID NO: 618 -12.7 -20.7 62.6 -8 0 -3.6

AATCCGATTTTAGCTCCATG 1022 SEQ ID NO: 619 -12.7 -22.9 65.5 -10.2 0 -4.8

CTCACTTCGCATGTAGATAT 1737 SEQ ID NO: 620 -12.7 -22.1 65.8 -9.4 0 -4.8

TGCAGGCTTTCTCCGTGGAC 1775 SEQ ID NO: 621 -12.7 -28.3 79.4 -15.1 -0.2 -5.6

CCAAGTCTCACCATATCTTC 1919 SEQ ID NO: 622 -12.7 -24 70.3 -11.3 0 -2.6

TCCCAAGTCTCACCATATCT 1921 SEQ ID NO: 623 -12.7 -25.9 73.6 -13.2 0 -2

GCACTGTACTCTTTAGAGCA 2510 SEQ ID NO: 624 -12.7 -23.9 71.8 -9.8 -1.3 -7

TATATGAAGTTAGGCTACCA 3467 SEQ ID NO: 625 -12.7 -20.8 62.6 -7.5 -0.3 -3.7

TCAAAACCCCAAGGTGACAA 3518 SEQ ID NO: 626 -12.7 -22.4 62 -8.8 -0.8 -4.2

TGGAAATTTTGTTTTGGTTT

3575 SEQ ID NO: 627 -12.7 -18.8 58.6 -6.1 0 -5.3 TTGGAAATTTTGTTTTGGTT

3576 SEQ ID NO:628 -12.7 -18.8 58.6 -6.1 0 -5.3 TTTGGAAATTTTGTTTTGGT

3577 SEQ ID NO: 629 -12.7 -18.8 58.6 -6.1 0 -4.7 TTTAGCTCCATGACACAGCA

1014 SEQ ID NO: 630 -12.6 -24.6 71 -10.6 -1.3 -5.2

ATAAAACTGACAGCCCAGGG 1359 SEQ ID NO: 631 -12.6 -23.1 64.6 -9.7 -0.6 -6.7

CACCTCGCCCTCGCCCTCGG 1518 SEQ ID NO: 632 -12.6 -36 86.9 -22.7 -0.5 -3.7

TCCTTCAAGTAGCCCTGAAA 1559 SEQ ID NO: 633 -12.6 -24.6 69.1 -11.4 -0.3 -3.5

AAGGTGCCATTTGGTAACCA 1643 SEQ ID NO: 634 -12.6 -24.7 69.4 -10.6 -1.4 -8.8

ATTTTCAATCTTTTCAGGGG 1719 SEQ ID NO: 635 -12.6 -21 64.3 -8.4 0 -1.7

AATCCTCTCTTTTGGGCCCA 1844 SEQ ID NO: 636 -12.6 -28.4 78.4 -13.9 0 -12

GGATAGCTTTTTTGACATCC 1897 SEQ ID NO: 637 -12.6 -22.6 67.4 -10 0 -4.8

ACCTGTTCAAATGGTTTCAG 1952 SEQ ID NO: 638 -12.6 -21.8 65 -9.2 0 -3.9

GAACACTTCCCTCTAGTGCA 2527 SEQ ID NO: 639 -12.6 -26 74 -11.9 -1.4 -5.3

CATTCTGCCATGAAAGAGAA 2809 SEQ ID NO: 640 -12.6 -20.3 59.9 -7.2 -0.1 -5.7

TGCAAGCCCTGTTGTGCTTG 3417 SEQ ID NO: 641 -12.6 -27.8 77.4 -12 -3.2 -8.8

ACACCAAGGGCTCGTCGCTG 244 SEQ ID NO: 642 -12.5 -28.5 76.4 -15 -0.9 -5.1

AAGCCATTCATAGGGTTGGT 357 SEQ ID NO: 643 -12.5 -24.8 72.1 -11.2 -1 -5.2

TCACCCACTCAGGTCTATTT 478 SEQ ID NO: 644 -12.5 -25.8 74.8 -12.8 -0.2 -3.6

TGGTATTAACTTATTTTCTA 651 SEQ ID NO: 645 -12.5 -17.4 56.3 -4.4 -0.2 -2.6

ATGTTTCGGTGAGTGACCAT 872 SEQ ID NO: 646 -12.5 -24.3 70.4 -10.1 -1.7 -4.3

TCTCTCAAACATATGGGCGA 978 SEQ ID NO: 647 -12.5 -22.5 64.9 -10 0 -6.7

107 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo άnding ation Duplex ture oligo oligo

TAGCTCCATGACACAGCATT

1012 SEQ ID NO: 648 -12.5 -24.5 70.6 -10.6 -1.3 -5.2 TTAGCTCCATGACACAGCAT

1013 SEQ ID NO: 649 -12.5 -24.5 70.6 -10.6 -1.3 -5.2 CGCTGGGTCCTTCAAGTAGC

1566 SEQ ID NO: 650 -12.5 -27.6 78 -15.1 0 -3.9

ATGCCTGCAGGCTTTCTCCG 1780 SEQ ID NO: 651 -12.5 -29.8 81.1 -12.8 -2.1 -17.2

CTTCGAGGATAGCTTTTTTG 1903 SEQ ID NO: 652 -12.5 -21.5 64.7 -9 0 -4.8

GTAAGGCGGTGTTCTGTTTC 2267 SEQ ID NO: 653 -12.5 -24.8 74 -12.3 0 -3.3

TACCATAAACATGGTCTGCA 2300 SEQ ID NO: 654 -12.5 -22 63.8 -7.4 -2.1 -8.7

CACATTTATAGTATCCCCTT 2355 SEQ ID NO:655 -12.5 -23.5 68 -11 0 -3.3

CAGTTGTTCTTATTTTTAAA 2549 SEQ ID NO: 656 -12.5 -17.1 55.5 -4.6 0 -4.2

GCATTCTGCCATGAAAGAGA 2810 SEQ ID NO: 657 -12.5 -22.8 65.8 -9.4 -0.7 -7.1

GGAGTCGGGGAATCAGGCCT 2848 SEQ ID NO: 658 -12.5 -28.7 78.9 -14.9 -0.9 -10

TAACTCTTTCTTGAAATGCT 2921 SEQ ID NO: 659 -12.5 -18.9 58.4 -5.7 -0.5 -5.2

GTACTGTCGGAAGTCAACCA 57 SEQ ID NO: 660 -12.4 -24 68.8 -11.1 -0.2 -4.5

TGTTGGTCGGAAGAGTACGC 79 SEQ ID NO: 661 -12.4 -24.3 69.7 -11.1 -0.6 -6.2

GAAATACACCAAGGGCTCGT 249 SEQ ID NO: 662 -12.4 -23.5 65.6 -11.1 0 -4.5

CCACACCTCTGGCCTCGTTC 719 SEQ ID NO: 663 -12.4 -30.8 82.9 -18.4 0 -7.2

ACTATGTTTCGGTGAGTGAC 875 SEQ ID NO: 664 -12.4 -22.4 67.5 -10 0 -3

TTCACACACACCTCGCCCTC 1526 SEQ ID NO: 665 -12.4 -29.3 78.5 -16.9 0 -2.7

ACCATAAACATGGTCTGCAA 2299 SEQ ID NO: 666 -12.4 -21.6 62.4 -7.4 -1.8 -10.2

AAGGGACAGTAGCAGGGATT 2611 SEQ ID NO: 667 -12.4 -23.7 69.6 -11.3 0 -4.1

CAAGAGCATTCTGCCATGAA 2815 SEQ ID NO: 668 -12.4 -22.9 65.7 -9.6 -0.7 -7.1

TTGAAATGCTTGTCTTCACT

2911 SEQ ID NO: 669 -12.4 -20.9 63.3 -7.9 -0.3 -3.6 CTTGAAATGCTTGTCTTCAC

2912 SEQ ID NO: 670 -12.4 -20.9 63.3 -7.9 -0.3 -3.6 TACTCCCTTAATAGCTTTAA

3116 SEQ ID NO: 671 -12.4 -20.8 62 -8.4 0 -5.6

ATTTCCCAAATTAACTTTAA 3286 SEQ ID NO: 672 -12.4 -17.3 53.6 -4.9 0 -3.2

CTGCTTTAAATGTACAAATG 3361 SEQ ID NO: 673 -12.4 -16.5 52.4 -4.1 0 -6.8

CTACCAAGTAGTGTTATTAC 3453 SEQ ID NO: 674 -12.4 -19.9 61.7 -7 -0.2 -3.9

ACCATTGCTCCTTTGGGGTT 857 SEQ ID NO: 675 -12.3 -28.1 78.8 -14.9 -0.7 -5.7

ACAGCATTACACACTCTACA 1000 SEQ ID NO: 676 -12.3 -22 65.5 -9.7 0 -4.1

AGGCTCACTTCGCATGTAGA 1740 SEQ ID NO: 677 -12.3 -25.4 73.7 -12.4 -0.5 -4.8

CATCTGGTACCACAATTGCA 1807 SEQ ID NO: 678 -12.3 -23.8 68 -10.6 0 -9.6

108 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTCATTGTTGGAGTCAGAAG 2018 SEQ ID NO: 679 -12.3 -20.6 63.9 -8.3 0 -4.7

TCCTAGAATTTTGGCTTGTC 3215 SEQ ID NO: 680 -12.3 -22.8 68.4 -10.5 0 -4.3

GCTGTTAATTTCCCAAATTA 3293 SEQ ID NO: 681 -12.3 -20.7 61 -7.2 -1.1 -8.2

CACCCACTCAGGTCTATTTT 477 SEQ ID NO: 682 -12.2 -25.5 73.4 -12.8 -0.2 -3.6

TCTACACCCTCTAATAAGAG 635 SEQ ID NO: 683 -12.2 -20.9 62.1 -7.1 -1.6 -4.8

GGCTTGGGCTTCCGTCTGTT 785 SEQ ID NO: 684 -12.2 -30.2 84.8 -16.6 -1.3 -7.2

GATTTTAGCTCCATGACACA 1017 SEQ ID NO: 685 -12.2 -22.8 67 -10.6 0 -4.8

GGTTCAGCAGTCTTGGAACC 1108 SEQ ID NO: 686 -12.2 -26 75.9 -11.8 -2 -6.6

AGCTCTGCTTCTTTCCTCTT 1196 SEQ ID NO: 687 -12.2 -27 80.6 -14.1 -0.4 -4.4

CCTGAGCAACAGGCTCACTT 1750 SEQ ID NO: 688 -12.2 -26.4 74.2 -10.1 -4.1 -9.5

AAATCCTCTCTTTTGGGCCC 1845 SEQ ID NO: 689 -12.2 -27 74.9 -13.9 0 -9.8

AGTCTCACCATATCTTCGAG

1916 SEQ ID NO: 690 -12.2 -23.4 69.4 -11.2 0 -4.8 AAGTCTCACCATATCTTCGA

1917 SEQ ID NO: 691 -12.2 -22.7 66.9 -10.5 0 -4.4 AACAACATGAAGGCCATCAG

2164 SEQ ID NO: 692 -12.2 -21.1 61.1 -8 0 -9.7

CCTAACCCCTTGATTAGAAA 2436 SEQ ID NO: 693 -12.2 -22.7 63.2 -10 -0.2 -3.4

ACTCTTTAGAGCAGCAGACA 2503 SEQ ID NO: 694 -12.2 -23.4 70.2 -9.8 -1.3 -7

AGCATTCTGCCATGAAAGAG 2811 SEQ ID NO: 695 -12.2 -22.2 64.7 -8.4 -1.5 -7.1

TGCTTGCCTGAGAGTTTATT 3091 SEQ ID NO: 696 -12.2 -23.9 70.7 -11.7 0 -3.9

ATACTCCCTTAATAGCTTTA 3117 SEQ ID NO: 697 -12.2 -21.5 64.1 -9.3 0 -4.6

TTATAAGAACATTTGCTTAT 3167 SEQ ID NO: 698 -12.2 -16.3 52.7 -3.2 -0.7 -4.2

TCAAATGTGGCAAAGACTCA

3327 SEQ ID NO: 699 -12.2 -20 59.7 -7.8 0 -4 GTCAAATGTGGCAAAGACTC

3328 SEQ ID NO:700 -12.2 -20.5 61.4 -7.8 -0.2 -4.6 CAAGTAGTGTTATTACAATG

3449 SEQ ID NO:701 -12.2 -17.1 55 -4.2 -0.5 -5.7

GGAAGAGTACGCACGTACTG 71 SEQ ID NO: 702 -12.1 -23.1 65.9 -9 -1.5 -11.9

GGGCAGTCTTGAAGCCCTTC 430 SEQ ID NO:703 -12.1 -28.6 80.7 -13.2 -3.3 -10.5

CTGATCTGGGGCAGTCTTGA 438 SEQ ID NO: 704 -12.1 -26.1 76.4 -13.1 -0.7 -4.9

TTAACTTATTTTCTACACCC 646 SEQ ID NO: 705 -12.1 -20.4 61.4 -8.3 0 -2

CTCTCAAACATATGGGCGAG 977 SEQ ID NO:706 -12.1 -22.1 63.7 -10 0 -6.8

CAGCAGTCTTGGAACCACGG 1104 SEQ ID NO: 707 -12.1 -26 72 -13.9 0 -5.5

TTCAGCAGTCTTGGAACCAC 1106 SEQ ID NO: 708 -12.1 -24.5 71.4 -12.4 0 -5.5

AATTCATTTCTTCCACATCA 1489 SEQ ID NO:709 -12.1 -21.2 63.9 -9.1 0 -2.3

109 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GTAATTCATTTCTTCCACAT

1491 SEQ ID NO:710 -12.1 -21 63.8 -8.9 0 -2.9 TGTAATTCATTTCTTCCACA

1492 SEQ ID NO:711 -12.1 -21 63.7 -8.9 0 -2.9 GGCAGCCATGTAATTCATTT

1500 SEQ ID NO:712 -12.1 -23.8 69 -11 -0.2 -8.6

ACACCTCGCCCTCGCCCTCG

1519 SEQ ID NO:713 -12.1 -35 85.2 -22.3 -0.3 -3 ATTTTCAAGGTGCCATTTGG

1649 SEQ ID NO:714 -12.1 -23 67.4 -10.9 0 -6.2

TGCTTTTTCCGGTCGATAAT 1667 SEQ ID NO:715 -12.1 -23.5 66.7 -11.4 0 -6.6

TGTGCCAGCTTAAATATGTG 1685 SEQ ID NO:716 -12.1 -21.7 63.9 -9.6 0 -4.5

TCAGAAGGCCATTGTCGATA 2005 SEQ ID NO:717 -12.1 -23.5 67.6 -10.9 0 -7.7

GGCGGTGTTCTGTTTCCTCT 2263 SEQ ID NO:718 -12.1 -28.8 83.2 -16.7 0 -4

AACTCTTTCTTGAAATGCTT 2920 SEQ ID NO:719 -12.1 -19.3 59.3 -6.6 -0.3 -5.2

TATAAGAACATTTGCTTATT 3166 SEQ ID NO:720 -12.1 -16.3 52.7 -3.2 -0.9 -4.2

TGACAATTCTTTAGTGCAAG 3431 SEQ ID NO:721 -12.1 -19.1 59.1 -7 0 -5.4

AACATTCAAAACCCCAAGGT 3523 SEQ ID NO:722 -12.1 -21.9 61.2 -8.6 -1.1 -3.9

GAGTACGCACGTACTGTCGG 67 SEQ ID NO: 723 -12 -25.6 71.3 -11.2 -2.1 -12.5

GCTCGTCGCTGTCAAGTAGT 235 SEQ ID NO:724 -12 -26.7 77.2 -14.2 -0.1 -4.2

ACCCACTCAGGTCTATTTTG 476 SEQ ID NO:725 -12 -24.8 72.1 -12.3 -0.1 -3.6

ATAATCACCCACTCAGGTCT 482 SEQ ID NO:726 -12 -24.9 71.5 -12.4 -0.2 -3.6

CACACCTCGCCCTCGCCCTC

1520 SEQ ID NO:727 -12 -34.9 86.8 -22.3 -0.3 -2.7 TTAAATATGTGCTTTTTCCG

1676 SEQ ID NO:728 -12 -19.6 58.9 -7.6 0 -3.6

CAAGTCTCACCATATCTTCG 1918 SEQ ID NO: 729 -12 -22.8 66.7 -10.8 0 -2.6

CATTTATAGTATCCCCTTTA 2353 SEQ ID NO:730 -12 -22.4 66.1 -10.4 0 -3

TGCACTGTACTCTTTAGAGC 2511 SEQ ID NO:731 -12 -23.2 70.5 -9.8 -1.3 -7.2

GAAGGGACAGTAGCAGGGAT 2612 SEQ ID NO:732 -12 -24.2 70.6 -12.2 0 -4.1

GGTAACTCTTTCTTGAAATG 2923 SEQ ID NO:733 -12 -18.6 58 -5.9 -0.5 -5

ACTCCCTTAATAGCTTTAAA 3115 SEQ ID NO:734 -12 -20.4 60.6 -8.4 0 -5.9

GAACTTTCCAGATTTCTACA 3235 SEQ ID NO:735 -12 -21 63.4 -9 0 -3.1

GTTTGGGTCTCGTGGCGTAC 142 SEQ ID NO: 736 -11.9 -27.6 79 -15.7 0 -4.2

CCTTGGAAAAATCCGATTTT 1031 SEQ ID NO:737 -11.9 -20.1 57.9 -7.1 -1 -9

ACATCCGGTTCAGCAGTCTT 1114 SEQ ID NO:738 -11.9 -26.8 77.2 -14.9 0 -6.6

CCATCGCTTCAGCGTGGTGT 1158 SEQ ID NO:739 -11.9 -29.2 80.2 -14.2 -3.1 -12.3

AGCCCAGGGCTGCTCTGAGG 1348 SEQ ID NO:740 -11.9 -31.4 86.4 -17 -2.2 -12.8

110 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TGCACGGCATCGGGGCCCCA

1453 SEQ ID NO: 741 -11.9 -34.5 85.4 -18.9 -1.7 -15.5 TCAAGTAGCCCTGAAATACA

1555 SEQ ID NO: 742 -11.9 -21.8 63.1 -9.4 -0.2 -3.5 ACTTGCTGTATTCAAAATTA

2183 SEQ ID NO: 743 -11.9 -17.7 55.6 -5.8 0 -3.6 GCCAGGACAGTTGTTCTTAT

2556 SEQ ID NO: 744 -11.9 -24.9 73.7 -13 0 -4.7 TGGAGTCGGGGAATCAGGCC

2849 SEQ ID NO: 745 -11.9 -27.8 76.8 -14.9 -0.9 -7.3 AAGGATGGAGTCGGGGAATC

2854 SEQ ID NO: 746 -11.9 -23.2 66.9 -10.8 -0.2 -4.7 ACCCCTGAAAAAGGATGGAG

2864 SEQ ID NO: 747 -11.9 -22.5 62.5 -9.4 -1.1 -4.9 ATTATAAGAACATTTGCTTA

3168 SEQ ID NO: 748 -11.9 -16.3 52.7 -4.4 0 -4.4 ATCCTAGAATTTTGGCTTGT

3216 SEQ ID NO: 749 -11.9 -22.4 66.8 -10.5 0 -3.8 AACCCCAAGGTGACAAATTA

3514 SEQ ID NO: 750 -11.9 -21.8 61.3 -8.5 -1.3 -5.7 TGGTCGGAAGAGTACGCACG

76 SEQ ID NO: 751 -11.8 -24.7 68.1 -12 -0.7 -6.2 GTGTTGGTCGGAAGAGTACG

80 SEQ ID NO: 752 -11.8 -23.7 68.7 -11.1 -0.6 -6.2 GGGCCATTATTTGACACCTG

314 SEQ ID NO: 753 -11.8 -25.5 71.3 -13.2 0 -7.6 ACAAGGGCCATTATTTGACA

318 SEQ ID NO: 754 -11.8 -22.6 65.2 -10.8 0 -7.4 CCCAGGGCTGCTCTGAGGAA

1346 SEQ ID NO: 755 -11.8 -29.5 80.2 -15.8 -1.2 -11.8 CCTTTCACACACACCTCGCC

1529 SEQ ID NO: 756 -11.8 -29 77.2 -17.2 0 -2.7 TTCAAGGTGCCATTTGGTAA

1646 SEQ ID NO: 757 -11.8 -23 67.1 -11.2 0 -5.8 CAAAATTAACAACATGAAGG

2171 SEQ ID NO: 758 -11.8 -13.9 46.5 -2.1 0 -5.2 GAACGCTTCCTTCCCTACAC

2201 SEQ ID NO: 759 -11.8 -27.2 73.8 -15.4 0 -3.6 TTCTGTTTCCTCTAGCATTC

2256 SEQ ID NO: 760 -11.8 -24.1 73.7 -12.3 0 -4.1 AAGTGTGTATTACCATAAAC

2310 SEQ ID NO: 761 -11.8 -17.8 55.7 -6 0 -3.6 AGAAGGGACAGTAGCAGGGA

2613 SEQ ID NO: 762 -11.8 -24.2 70.9 -12.4 0 -4.1 TGAGTTGGATCTGCCCTCCC

2735 SEQ ID NO: 763 -11.8 -30.1 82.4 -17.6 -0.5 -5 GATTTTTAAATAACCCCTGA

2876 SEQ ID NO: 764 -11.8 -20 58.5 -7.6 -0.3 -4.5 ACCCCAAGGTGACAAATTAT

3513 SEQ ID NO: 765 -11.8 -22.5 63.1 -9.8 -0.8 -4.8 GAAGAGTACGCACGTACTGT

70 SEQ ID NO: 766 -11.7 -23.1 66.5 -9 -2.1 -12.5 ATCACCCACTCAGGTCTATT

479 SEQ ID NO: 767 -11.7 -25.7 74.3 -13.5 -0.2 -3.6 TAATCACCCACTCAGGTCTA

481 SEQ ID NO: 768 -11.7 -24.6 71 -12.4 -0.1 -3.6 AAAAACCAGAGAGAGTTCAG

591 SEQ ID NO: 769 -11.7 -18.3 56.3 -6 -0.3 -3.4 TCTCAAACATATGGGCGAGA

976 SEQ ID NO: 770 -11.7 -21.8 63.1 -9.6 -0.1 -8 TGGAAAAATCCGATTTTAGC

1028 SEQ ID NO: 771 -11.7 -18.6 55.7 -5.6 -1.2 -9.3

111 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CAAAGTCCAAGAGCCATCGC 1171 SEQ ID NO:772 -11.7 -25 68.8 -12.6 -0.4 -3.2

GCGGCTCCTGTCACCATCAG 1301 SEQ ID NO:773 -11.7 -30.1 82.2 -17.9 -0.1 -5.3

CATAAAACTGACAGCCCAGG 1360 SEQ ID NO:774 -11.7 -22.6 63.4 -10.1 -0.6 -4.3

CTTTCACACACACCTCGCCC 1528 SEQ ID NO:775 -11.7 -29 77.2 -17.3 0 -2.7

CATGTAGATATTTTCAATCT 1728 SEQ ID NO:776 -11.7 -17.9 57.1 -5.7 -0.1 -3.7

CTTTTTTGACATCCTTATTT 1891 SEQ ID NO:777 -11.7 -20.2 62 -8.5 0 -2.2

TATCTTCGAGGATAGCTTTT 1906 SEQ ID NO: 778 -11.7 -21.4 65 -8.9 -0.4 -9

GCACATTTATAGTATCCCCT 2356 SEQ ID NO: 779 -11.7 -25.2 71.9 -13.5 0 -3.4

ATTCTGCCATGAAAGAGAAT 2808 SEQ ID NO:780 -11.7 -19.6 58.7 -7.2 -0.5 -5.7

CCTAGAATTTTGGCTTGTCA 3214 SEQ ID NO:781 -11.7 -23.1 68 -10.5 -0.7 -8.8

TTTCCCAAATTAACTTTAAA 3285 SEQ ID NO:782 -11.7 -16.6 52 -4.9 0 -4

GTTTTTGGAAATTTTGTTTT 3580 SEQ ID NO:783 -11.7 -17.8 56.8 -6.1 0 -5.3

CGAAATGCAGAAATATTTAT 3616 SEQ ID NO:784 -11.7 -15.3 49.3 -3.6 0 -6.7

CAGAGAGAGTTCAGCTTTGT 585 SEQ ID NO: 785 -11.6 -23 70.8 -10.8 -0.3 -4.7

ATTTTAGCTCCATGACACAG 1016 SEQ ID NO:786 -11.6 -22.2 65.9 -10.6 0 -4.5

ATCCGATTTTAGCTCCATGA 1021 SEQ ID NO:787 -11.6 -24.2 68.9 -12.6 0 -4.8

TTTCGCTGGGTCCTTCAAGT 1569 SEQ ID NO:788 -11.6 -26.7 76.3 -15.1 0 -3.6

GTGCCAGCTTAAATATGTGC 1684 SEQ ID NO:789 -11.6 -23.5 68.2 -11.9 0 -4.3

GCCTTTGACCTGTTCAAATG 1959 SEQ ID NO:790 -11.6 -23.6 67.3 -10 -2 -7.4

GTGTTCTGTTTCCTCTAGCA 2259 SEQ ID NO:791 -11.6 -26 78.9 -14.4 0 -4.1

ACATTTATAGTATCCCCTTT 2354 SEQ ID NO:792 -11.6 -22.9 67.2 -11.3 0 -3.3

TAACTTAGCACATTTATAGT 2363 SEQ ID NO:793 -11.6 -18.1 57.4 -6.5 0 -4.1

AGTCCTAACCCCTTGATTAG 2439 SEQ ID NO:794 -11.6 -25.1 70.7 -13.5 0 -3.1

CTGAAAAAGGATGGAGTCGG 2860 SEQ ID NO:795 -11.6 -19.9 58.5 -7.8 -0.2 -4.7

TTTTGGAAATTTTGTTTTGG 3578 SEQ ID NO:796 -11.6 -17.7 56 -6.1 0 -5.3

CTGTCGGAAGTCAACCAGCT 54 SEQ ID NO: 797 -11.5 -25.6 71.8 -14.1 0.3 -4.3

AAGAGTACGCACGTACTGTC 69 SEQ ID NO:798 -11.5 -22.9 66.7 -9 -2.1 -12.5

CTGACTGCATGGAGAGGTCG 178 SEQ ID NO:799 -11.5 -25.1 71.8 -12.5 -1 -5.6

CTGGGGCAGTCTTGAAGCCC 433 SEQ ID NO: 800 -11.5 -29.3 80.9 -14.5 -3.3 -10.5

AGTCTTGGAACCACGGGGAA 1100 SEQ ID NO:801 -11.5 -25.1 69.5 -12.8 -0.6 -6.5

TCACACACACCTCGCCCTCG 1525 SEQ ID NO: 802 -11.5 -30 77.8 -18 -0.1 -2.7

112 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CAAGTAGCCCTGAAATACAT 1554 SEQ ID NO: 803 -11.5 -21.4 61.7 -9.4 -0.2 -3.5

CTCTCTTTTGGGCCCAGGAA 1840 SEQ ID NO: 804 -11.5 -27.8 77.4 -14.2 0 -12.4

TCTTCGAGGATAGCTTTTTT 1904 SEQ ID NO: 805 -11.5 -21.9 66.3 -10.4 0 -6

AGGCCATCAGCAGGAGAAGA 2154 SEQ ID NO:806 -11.5 -25.6 73.1 -12.6 -1.4 -7.7

TGTAAGGCGGTGTTCTGTTT 2268 SEQ ID NO: 807 -11.5 -24.4 72.1 -12.9 0 -4

TTTGGAAAGTGTGTATTACC 2316 SEQ ID NO:808 -11.5 -19.9 60.9 -8.4 0 -3.4

TTTTTAAGGCTCATTTTGGA 2330 SEQ ID NO: 809 -11.5 -20.5 62.8 -9 0 -4.3

ATTTATAGTATCCCCTTTAC 2352 SEQ ID NO: 810 -11.5 -21.9 65.4 -10.4 0 -3.3

GTCCTAACCCCTTGATTAGA 2438 SEQ ID NO: 811 -11.5 -25.7 71.7 -13.7 -0.2 -3.4

CGTTCTGATGAGCACCCATT 2783 SEQ ID NO:812 -11.5 -26.1 72.3 -14 -0.3 -4.1

AATTTCCCAAATTAACTTTA 3287 SEQ ID NO:813 -11.5 -17.3 53.6 -4.9 -0.7 -3.7

CTGCTGTTAATTTCCCAAAT 3295 SEQ ID NO:814 -11.5 -21.8 63 -10.3 0 -3.6

TGTGGCAAAGACTCACAATA

3322 SEQ ID NO:815 -11.5 -20.2 60.2 -7.4 -1.2 -4.8 ATGTGGCAAAGACTCACAAT

3323 SEQ ID NO: 816 -11.5 -20.5 60.8 -7.4 -1.6 -5.7 TCGGAAGTCAACCAGCTCTG

51 SEQ ID NO: 817 -11.4 -24.8 70.2 -12.9 -0.2 -4.5

CCATTATTTGACACCTGTAT 311 SEQ ID NO:818 -11.4 -22.2 64.8 -10.8 0 -3.6

CCTATGCACTCCGACAATTC 395 SEQ ID NO:819 -11.4 -24.7 68.6 -13.3 0 -5.5

CTTCATTTCCAAGGGTATCA 547 SEQ ID NO: 820 -11.4 -23.1 68.4 -11.7 0 -3.6

GTTCCACCAGTTCACTGCCG

703 SEQ ID NO: 821 -11.4 -29.4 80 -17.5 -0.1 -6.4 CGTTCCACCAGTTCACTGCC

704 SEQ ID NO: 822 -11.4 -29.4 80 -17.5 -0.1 -6.4 TGGCTCTTCCCAGGTCCTCC

766 SEQ ID NO: 823 -11.4 -32.5 89.8 -20.6 -0.2 -4.5

CATATGGGCGAGAGGCAAGA 969 SEQ ID NO: 824 -11.4 -24.2 68.1 -11.2 -1.5 -7.4

CTCAAACATATGGGCGAGAG 975 SEQ ID NO: 825 -11.4 -21.4 62 -10 0 -6.7

CTGTCACCATCAGCCGGACT 1294 SEQ ID NO:826 -11.4 -28.7 78.1 -16.5 -0.6 -8.2

ATGTAATTCATTTCTTCCAC

1493 SEQ ID NO: 827 -11.4 -20.3 62.4 -8.9 0 -3.9 CATGTAATTCATTTCTTCCA

1494 SEQ ID NO: 828 -11.4 -20.8 63.1 -8.9 -0.2 -4.2 CTGCTGTTTTCGCTGGGTCC

1576 SEQ ID NO: 829 -11.4 -29 81.8 -16.5 -1 -3.9

GCAGGCTTTCTCCGTGGACA 1774 SEQ ID NO:830 -11.4 -29 80.7 -17.1 -0.2 -5.6

GCCCAGGAACATAATGTCTC 1829 SEQ ID NO: 831 -11.4 -24.4 69.4 -12.5 -0.2 -4.4

CCTTCATTGTTGGAGTCAGA 2020 SEQ ID NO: 832 -11.4 -24.2 72.1 -12.3 -0.2 -4.7

ACAACATGAAGGCCATCAGC 2163 SEQ ID NO:833 -11.4 -23.6 67 -11.3 -0.3 -9.7

113 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TATTCAAAATTAACAACATG 2175 SEQ ID NO: 834 -11.4 -13 45.2 -1.5 0 -4.7

CTAACCCCTTGATTAGAAAA 2435 SEQ ID NO: 835 -11.4 -20 58 -8.6 0 -3

GCCTGAGAGTTTATTTTTTG 3086 SEQ ID NO: 836 -11.4 -21.5 65.6 -10.1 0 -2

ACATTCAAAACCCCAAGGTG 3522 SEQ ID NO:837 -11.4 -22.6 62.9 -9.8 -1.3 -4.7

CCATTCATAGGGTTGGTCTG 354 SEQ ID NO: 838 -11.3 -25 73.4 -13.7 0 -3.1

GGCAGTCTTGAAGCCCTTCT 429 SEQ ID NO: 839 -11.3 -28.3 80.1 -15.8 -1.1 -6.7

CAGGTCTATTTTGAGCAAAG 469 SEQ ID NO: 840 -11.3 -20.1 61.5 -8.8 0 -5.9

GTCCTCCATCGCCTTCATGC 753 SEQ ID NO: 841 -11.3 -30.5 83.3 -19.2 0 -4.4

GGCTCTTCCCAGGTCCTCCA 765 SEQ ID NO: 842 -11.3 -33.2 91 -20.6 -1.2 -5.6

AGCTCCATGACACAGCATTA 1011 SEQ ID NO: 843 -11.3 -24.5 70.6 -11.8 -1.3 -5.2

AAAGTCCAAGAGCCATCGCT 1170 SEQ ID NO: 844 -11.3 -25.2 69.5 -12.6 -1.2 -4

CGGACTCTTCCGCCCAGGCT 1280 SEQ ID NO: 845 -11.3 -32.7 84 -19 -2.4 -10.5

GACACCGGGGCGGCTCCTGT 1310 SEQ ID NO: 846 -11.3 -33.1 85.2 -20.1 -1.7 -10.2

TAATTCATTTCTTCCACATC 1490 SEQ ID NO: 847 -11.3 -20.2 62 -8.9 0 -2.9

TTCAAGTAGCCCTGAAATAC 1556 SEQ ID NO: 848 -11.3 -21.2 62.2 -9.4 -0.1 -4.4

CCTTTTCGCCTTCATTGTTG 2028 SEQ ID NO: 849 -11.3 -25.7 72.7 -14.4 0 -2.7

AAGGCCATCAGCAGGAGAAG 2155 SEQ ID NO: 850 -11.3 -24.3 69.4 -11.5 -1.4 -7.7

CGCTTCCTTCCCTACACTTG 2198 SEQ ID NO: 851 -11.3 -28.1 76.4 -16.8 0 -3.1

TCTAGCATTCCTATGAGAAG 2246 SEQ ID NO: 852 -11.3 -21.1 63.9 -9.8 0.2 -4.1

TCCTAACCCCTTGATTAGAA 2437 SEQ ID NO: 853 -11.3 -23.8 66.5 -12 -0.2 -3.4

GTTGGATCTGCCCTCCCGCT 2732 SEQ ID NO: 854 -11.3 -33 86.6 -21.1 -0.3 -6.3

TGCCAGAGGCTCCTTATCTG 2763 SEQ ID NO: 855 -11.3 -27.4 77.9 -14 -2.1 -7.5

TTTATTTTTTGGGGAAAAAG 3077 SEQ ID NO: 856 -11.3 -15.8 51.2 -2.7 -1.8 -5

ATAAGAACATTTGCTTATTA 3165 SEQ ID NO: 857 -11.3 -16.3 52.7 -4.2 -0.6 -4.1

TGAACTTTCCAGATTTCTAC 3236 SEQ ID NO: 858 -11.3 -20.3 62 -9 0 -3.1

TGATCTGGGGCAGTCTTGAA 437 SEQ ID NO:859 -11.2 -24.5 71.8 -12.4 -0.7 -4.9

TGTTTCGGTGAGTGACCATT 871 SEQ ID NO: 860 -11.2 -24.4 70.8 -11.5 -1.7 -4.3

CAAACATATGGGCGAGAGGC 973 SEQ ID NO: 861 -11.2 -23.1 65.1 -11.2 -0.4 -7.4

TGTGGAAGATCAGCCGGTCC 1249 SEQ ID NO: 862 -11.2 -27.4 75.9 -15.7 -0.2 -7.4

TTTGTGGAAGATCAGCCGGT 1251 SEQ ID NO:863 -11.2 -25.2 71.5 -14 0.2 -7.7

TCATAAAACTGACAGCCCAG 1361 SEQ ID NO:864 -11.2 -21.8 62.3 -10.1 -0.2 -4.1

114 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTCATAAAACTGACAGCCCA 1362 SEQ ID NO: 865 -11.2 -21.9 62.5 -10.7 0 -4.1

TCGCCCTCGCCCTCGGCAGC 1514 SEQ ID NO: 866 -11.2 -36.5 90 -23.1 -2.2 -7.4

TTTCACACACACCTCGCCCT 1527 SEQ ID NO: 867 -11.2 -29 77.2 -17.8 0 -2.7

TTCGCTGGGTCCTTCAAGTA 1568 SEQ ID NO: 868 -11.2 -26.3 75.4 -15.1 0 -3.6

CAGCTTAAATATGTGCTTTT 1680 SEQ ID NO: 869 -11.2 -19.7 60.3 -7.8 -0.4 -4.5

TACTCTTTAGAGCAGCAGAC 2504 SEQ ID NO: 870 -11.2 -22.4 68.4 -9.8 -1.3 -7

GTGCACTGTACTCTTTAGAG 2512 SEQ ID NO: 871 -11.2 -22.6 69.4 -9.8 -1.1 -10.8

AGGGAACACTTCCCTCTAGT 2530 SEQ ID NO: 872 -11.2 -25.9 74.3 -10.6 -4.1 -12.8

CCAAGAGCATTCTGCCATGA 2816 SEQ ID NO: 873 -11.2 -25.6 71.4 -12.8 -1.5 -7.1

ACACAGAGTGAGTGGTTCAG 2996 SEQ ID NO: 874 -11.2 -23 70.2 -10.7 -1 -6.1

GCAAGCCCTGTTGTGCTTGT 3416 SEQ ID NO: 875 -11.2 -29 81.1 -14.3 -3.5 -9.3

ATATATGAAGTTAGGCTACC 3468 SEQ ID NO: 876 -11.2 -20.1 61.4 -8.9 0 -3.7

TAACTTATTTTCTACACCCT 645 SEQ ID NO: 877 -11.1 -21.2 63 -10.1 0 -1.2

AGTTCACTGCCGTAGGCATC 695 SEQ ID NO: 878 -11.1 -27.1 77.6 -11.5 -4.5 -11.1

CTCTGTTGCTTTCACAAAAG 909 SEQ ID NO: 879 -11.1 -20.3 61.4 -8 -1.1 -5.1

TATCTCCTTGGAAAAATCCG 1036 SEQ ID NO: 880 -11.1 -20.6 59.4 -8.6 -0.7 -5.2

TCAGCAGTCTTGGAACCACG 1105 SEQ ID NO: 881 -11.1 -25.2 71 -14.1 0 -5.5

TGGTGTTTGCTTGTCCGAAA 1144 SEQ ID NO: 882 -11.1 -24.2 69 -13.1 0 -3.6

ACACCGGGGCGGCTCCTGTC 1309 SEQ ID NO: 883 -11.1 -32.9 85.7 -20.1 -1.7 -9.3

ATTCATTTCTTCCACATCAA 1488 SEQ ID NO: 884 -11.1 -21.2 63.9 -10.1 0 -0.9

ACATTTGGCCCTTTCACACA 1538 SEQ ID NO:885 -11.1 -26.1 72.9 -15 0 -6.6

TCGCTGGGTCCTTCAAGTAG 1567 SEQ ID NO: 886 -11.1 -26.2 75.3 -15.1 0 -3.3

TTTTTGACATCCTTATTTCT 1889 SEQ ID NO: 887 -11.1 -20.5 63.1 -9.4 0 -2.2

TTGTCGATAGAAAATAATTC 1994 SEQ ID NO: 888 -11.1 -14.8 49.1 -2.5 -1.1 -8.7

GGCCATTGTCGATAGAAAAT 1999 SEQ ID NO:889 -11.1 -21 60.8 -9.9 2.5 0

GAAGGCCATCAGCAGGAGAA 2156 SEQ ID NO: 890 -11.1 -24.9 70.5 -12.3 -1.4 -8.1

TTCAAAATTAACAACATGAA 2173 SEQ ID NO: 891 -11.1 -13.2 45.4 -2.1 0 -5.2

GCCAGAGGCTCCTTATCTGC 2762 SEQ ID NO: 892 -11.1 -29.2 82.6 -16.6 -1.4 -6.7

ATTTTTAAATAACCCCTGAA 2875 SEQ ID NO: 893 -11.1 -18.7 55.6 -7.6 0 -4.5

TTGATATGAAAACCACATTA 3033 SEQ ID NO: 894 -11.1 -16.5 51.9 -5.4 0 -3

GCTTATTACTGTCCATTTCA 3153 SEQ ID NO: 895 -11.1 -23 68.9 -11.9 0 -3

115 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CATTATAAGAACATTTGCTT

3169 SEQ ID NO: 896 -11.1 -17.3 54.6 -6.2 0 -4.4 TACCAAGTAGTGTTATTACA

3452 SEQ ID NO: 897 -11.1 -19.7 61 -8 -0.3 -5.7 CTCGTTCCACCAGTTCACTG

706 SEQ ID NO: 898 -11 -26.9 75.9 -15.9 0 -6.1 GTATTCTCTGTTGCTTTCAC

914 SEQ ID NO: 899 -11 -23.1 71.7 -12.1 0 -3.6 ACATATGGGCGAGAGGCAAG

970 SEQ ID NO: 900 -11 -23.8 67.4 -11.2 -1.5 -8.6 ACTCTCTCAAACATATGGGC

980 SEQ ID NO: 901 -11 -22.-2 65.8 -11.2 0 -6.7 TTGTGGAAGATCAGCCGGTC

1250 SEQ ID NO: 902 -11 -25.5 72.7 -14 -0.2 -7.7 GCCGGACTCTTCCGCCCAGG

1282 SEQ ID NO: 903 -11 -33.8 85.4 -19.9 -2.9 -9.7 AAATTGCACGGCATCGGGGC

1457 SEQ ID NO: 904 -11 -26.5 70.8 -14.6 -0.8 -7.3 CCTCGCCCTCGCCCTCGGCA

1516 SEQ ID NO: 905 -11 -37.6 90.3 -24.4 -2.2 -7.2 ATACATTTGGCCCTTTCACA

1540 SEQ ID NO: 906 -11 -24.9 70.7 -13.9 0 -6.6 AATGCCTGCAGGCTTTCTCC

1781 SEQ ID NO: 907 -11 -28.3 79 -12.8 -2.1 -17.2 TTTTGACATCCTTATTTCTG

1888 SEQ ID NO: 908 -11 -20.4 62.6 -9.4 0 -2.2 TCAAAATTAACAACATGAAG

2172 SEQ ID NO: 909 -11 -13.1 45.2 -2.1 0 -5.2 CTTGCTGTATTCAAAATTAA

2182 SEQ ID NO: 910 -11 -16.8 53.3 -5.8 0 -3.6 CTGTACTCTTTAGAGCAGCA

2507 SEQ ID NO: 911 -11 -23.7 71.5 -11.7 -0.9 -6.6 AACACTTCCCTCTAGTGCAC

2526 SEQ ID NO: 912 -11 -25.6 73.3 -13.1 -1.4 -8.6 GGACAGTAGCAGGGATTTAA

2608 SEQ ID NO: 913 -11 -22.3 66.5 -11.3 0 -4.1 GAGAAGGGACAGTAGCAGGG

2614 SEQ ID NO: 914 -11 -24.2 70.9 -13.2 0 -4.1 ATCCCTGGAGAAGTGAATCC

3263 SEQ ID NO: 915 -11 -24.5 69.3 -13 -0.2 -4.8 TAATTTCCCAAATTAACTTT

3288 SEQ ID NO: 916 -11 -17.3 53.6 -4.9 -1.3 -4.9 TGGGCTTGCATTGTCCTGTG

5 SEQ ID NO: 917 -10.9 -27.5 78.6 -15.9 -0.5 -8 CACAGCATTACACACTCTAC

1001 SEQ ID NO: 918 -10.9 -22 65.5 -11.1 0 -4.1 CAGTCTTGGAACCACGGGGA

1101 SEQ ID NO: 919 -10.9 -26.5 72.7 -14.8 -0.6 -6.5 GCACGGCATCGGGGCCCCAA

1452 SEQ ID NO: 920 -10.9 -33.8 83.2 -19.8 -1.6 -14.4 CATTTGGCCCTTTCACACAC

1537 SEQ ID NO: 921 -10.9 -26.1 72.9 -15.2 0 -5.9 AAGTAGCCCTGAAATACATT

1553 SEQ ID NO: 922 -10.9 -20.8 60.9 -9.4 -0.2 -3.5 CTGGGTCCTTCAAGTAGCCC

1564 SEQ ID NO: 923 -10.9 -29 81.1 -17.2 -0.7 -5.2 ACCTGAGCAACAGGCTCACT

1751 SEQ ID NO: 924 -10.9 -26.5 74.4 -11.5 -4.1 -10.5 TCTGGTACCACAATTGCAAT

1805 SEQ ID NO: 925 -10.9 -22.4 64.7 -10.6 0 -9.6 ATCTGGTACCACAATTGCAA

1806 SEQ ID NO: 926 -10.9 -22.4 64.7 -10.6 0 -9.6

116 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTCCCAAGTCTCACCATATC 1922 SEQ ID NO: 927 -10.9 -25.1 72 -14.2 0 -2

CCTTCCCAAGTCTCACCATA 1924 SEQ ID NO: 928 -10.9 -27.6 75.9 -16.7 0 -2.3

TGCTGTATTCAAAATTAACA 2180 SEQ ID NO: 929 -10.9 -16.7 53 -5.8 0 -3.6

AAGTCCTAACCCCTTGATTA 2440 SEQ ID NO: 930 -10.9 -24.4 68.2 -13.5 0 -2.3

TTCTCCAGCCAGGACAGTTG 2563 SEQ ID NO:931 -10.9 -27 77.3 -15 -1 -5.2

CCTGAAAAAGGATGGAGTCG 2861 SEQ ID NO:932 -10.9 -20.7 59.7 -9 -0.6 -5.9

ATGCTTGCCTGAGAGTTTAT 3092 SEQ ID NO:933 -10.9 -23.8 70.3 -12.9 0 -3.9

TATACTCCCTTAATAGCTTT 3118 SEQ ID NO:934 -10.9 -21.5 64.1 -10.6 0 -4.6

TTCCCAAATTAACTTTAAAA 3284 SEQ ID NO: 935 -10.9 -15.8 50.1 -4.9 0 -4.3

AAATGTGGCAAAGACTCACA 3325 SEQ ID NO: 936 -10.9 -19.8 58.9 -7.4 -1.4 -5.3

CCCAAGGTGACAAATTATTG 3511 SEQ ID NO: 937 -10.9 -20.4 59.4 -8.6 -0.7 -4.3

AAACATTCAAAACCCCAAGG 3524 SEQ ID NO:938 -10.9 -20 56.9 -8.6 -0.1 -3.2

TTTCCTTCATTGTTTTTGGA 3591 SEQ ID NO:939 -10.9 -22.2 67.3 -11.3 0 -3.9

GTATTAACTTATTTTCTACA 649 SEQ ID NO: 940 -10.8 -17.1 55.6 -6.3 0 -2.9

TTCCACCAGTTCACTGCCGT 702 SEQ ID NO: 941 -10.8 -29.4 80 -18.1 -0.1 -6.4

GCTCCATGACACAGCATTAC 1010 SEQ ID NO: 942 -10.8 -24.7 70.9 -13.2 -0.5 -4.6

GGAAAAATCCGATTTTAGCT 1027 SEQ ID NO: 943 -10.8 -19.5 57.5 -7.4 -1.2 -9.3

GCCGTCTTTGTCCAAAGCTT 1596 SEQ ID NO: 944 -10.8 -27 74.9 -15.5 -0.5 -8.2

AATAATTCAGGGTGCAATGT 1982 SEQ ID NO: 945 -10.8 -20.1 60.6 -9.3 0 -5.4

CATGAGTTTCGTAACCCTTA 2663 SEQ ID NO: 946 -10.8 -23 66.2 -12.2 0.3 -5.5

TCTTGAAATGCTTGTCTTCA 2913 SEQ ID NO: 947 -10.8 -21.1 64.2 -9.8 -0.1 -3.6

AATGTGGCAAAGACTCACAA 3324 SEQ ID NO: 948 -10.8 -19.8 58.9 -7.4 -1.6 -5.7

ACGTACTGTCGGAAGTCAAC 59 SEQ ID NO: 949 -10.7 -22.3 64.8 -11.1 -0.2 -5.5

CACCAAGGGCTCGTCGCTGT 243 SEQ ID NO: 950 -10.7 -29.5 79.1 -17.8 -0.9 -5.1

CTATGCACTCCGACAATTCT 394 SEQ ID NO: 951 -10.7 -23.6 66.9 -12.9 0 -5.5

AGAGTTTGGCCTTCTCTGGC 619 SEQ ID NO: 952 -10.7 -27.6 81 -15.3 -1.5 -9.1

CTCTCTCAAACATATGGGCG 979 SEQ ID NO: 953 -10.7 -22.8 65.5 -12.1 0 -6.7

CCTTGAGGTCATCCATGAGC 1063 SEQ ID NO: 954 -10.7 -26.6 76 -14.6 -1.2 -0.1

GCCTGCAGGCTTTCTCCGTG 1778 SEQ ID NO: 955 -10.7 -31 84.8 -16.2 -1.4 -16.4

ATCCTCTCTTTTGGGCCCAG 1843 SEQ ID NO: 956 -10.7 -29.1 81.3 -16.3 0 -12.4

GGCCATCAGCAGGAGAAGAG 2153 SEQ ID NO: 957 -10.7 -25.6 73.1 -13.4 -1.4 -7.3

117 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular ' position oligo linding ation Duplex ture oligo oligo

CGAACGCTTCCTTCCCTACA 2202 SEQ ID NO: 958 -10.7 -27.8 73.2 -17.1 0 -4.2

TCCCCTTTACAATTTTTAAG 2342 SEQ ID NO: 959 -10.7 -20.8 61.2 -10.1 0 -2.6

AGTGCACTGTACTCTTTAGA 2513 SEQ ID NO: 960 -10.7 -22.6 69.4 -10.8 0 -10.1

AGGATGGAGTCGGGGAATCA 2853 SEQ ID NO: 961 -10.7 -24.6 70.3 -12.9 -0.9 -4.7

ATAACCCCTGAAAAAGGATG 2867 SEQ ID NO: 962 -10.7 -19.7 56.8 -7.8 -1.1 -4.1

TGAAATGCTTGTCTTCACTA 2910 SEQ ID NO: 963 -10.7 -20.5 62.4 -9.3 -0.1 -3.6

CTGTTAATTTCCCAAATTAA 3292 SEQ ID NO: 964 -10.7 -18.2 55.4 -4.9 -2.6 -7.5

CAAATGTGGCAAAGACTCAC 3326 SEQ ID NO:965 -10.7 -19.8 58.9 -9.1 0.6 -4

AAACAGCTGCTTTAAATGTA 3367 SEQ ID NO: 966 -10.7 -18.3 56.3 -6.9 0 -8.9

ACCCCAAAACAGCTGCTTTA 3373 SEQ ID NO: 967 -10.7 -25 68.1 -13.6 0 -9.1

CTGGCATTCGAAAATACCGG 34 SEQ ID NO: 968 -10.6 -22.3 61.6 -11.7 0 -7.3

CGTATAATGTTGTGACATCA 274 SEQ ID NO: 969 -10.6 -19.8 60 -7.5 -1.7 -6.2

CCTAAACAAGGGCCATTATT 323 SEQ ID NO: 970 -10.6 -22.2 62.9 -10.8 -0.6 -8

GTGGTGTTTGCTTGTCCGAA 1145 SEQ ID NO: 971 -10.6 -26.1 74.6 -15.5 0 -3.6

TCAGCGTGGTGTTTGCTTGT 1150 SEQ ID NO: 972 -10.6 -26.7 78.1 -15.3 -0.6 -4.6

CCATGTAATTCATTTCTTCC 1495 SEQ ID NO: 973 -10.6 -22.1 65.7 -11 -0.2 -4.3

CACACACACCTCGCCCTCGC 1524 SEQ ID NO: 974 -10.6 -31.4 80.1 -20.2 -0.3 -2.7

GTCTCACCATATCTTCGAGG 1915 SEQ ID NO:975 -10.6 -24.6 71.8 -14 0 -4.8

TCTGGCCTTTTCGCCTTCAT 2033 SEQ ID NO: 976 -10.6 -28.6 79.2 -16.2 -1.8 -7.2

GTATTCAAAATTAACAACAT 2176 SEQ ID NO: 977 -10.6 -14.2 47.6 -3.6 0 -3.2

CCATAAACATGGTCTGCAAC 2298 SEQ ID NO: 978 -10.6 -21.6 62.4 -10.3 -0.5 -5.9

ACATGAGTTTCGTAACCCTT 2664 SEQ ID NO: 979 -10.6 -23.5 67.3 -12.2 -0.5 -6.1

GCGTTCTGATGAGCACCCAT 2784 SEQ ID NO: 980 -10.6 -27.8 76.1 -16.6 -0.3 -4.4

TGCTGTTAATTTCCCAAATT 3294 SEQ ID NO: 981 -10.6 -21 61.5 -9.5 -0.8 -5.2

AGTCAAATGTGGCAAAGACT 3329 SEQ ID NO: 982 -10.6 -20.1 60.2 -8.4 -1 -5.9

CCCCAAAACAGCTGCTTTAA 3372 SEQ ID NO:983 -10.6 -24.1 65.6 -12.8 0 -8.9

CAAACATTCAAAACCCCAAG 3525 SEQ ID NO:984 -10.6 -19.5 55.9 -8.9 0 -1.4

TTGGTCGGAAGAGTACGCAC 77 SEQ ID NO: 985 -10.5 -24 68.3 -12.7 -0.6 -6.2

ACTGACTGCATGGAGAGGTC 179 SEQ ID NO: 986 -10.5 -24.5 72.4 -14 0 -5

CAAGTAGTGCGGATCTTCGT 223 SEQ ID NO: 987 -10.5 -24.3 70 -13.2 -0.3 -5

TGACACCTGTATTCCCCTCT 303 SEQ ID NO: 988 -10.5 -28.2 77.7 -17.7 0 -3.6

118 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTGGCCTCGTTCCACCAGTT 711 SEQ ID NO: 989 -10.5 -30.6 82.8 -18.5 -1.5 -7.2

AGGCTTGGGCTTCCGTCTGT 786 SEQ ID NO: 990 -10.5 -30.1 84.8 -18.2 -1.3 -7.2

CGATTTTAGCTCCATGACAC 1018 SEQ ID NO: 991 -10.5 -22.9 66.1 -12.4 0 -4.8

TCTTGGAACCACGGGGAAGA 1098 SEQ ID NO: 992 -10.5 -24.5 67.7 -13.2 -0.6 -6.5

GCAGTCTTGGAACCACGGGG 1102 SEQ ID NO: 993 -10.5 -27.7 75.6 -16.7 -0.2 -6.1

GGGCGGCTCCTGTCACCATC 1303 SEQ ID NO: 994 -10.5 -31.8 86.1 -20.5 -0.6 -6.8

GTGCACTCTGTCTGTCCGTA

1385 SEQ ID NO: 995 -10.5 -27.9 81.1 -16.8 0 -8.6 AGTGCACTCTGTCTGTCCGT

1386 SEQ ID NO: 996 -10.5 -28.2 82.1 -16.6 0 -10.1 TTTTCGCTGGGTCCTTCAAG

1570 SEQ ID NO: 997 -10.5 -25.6 73.3 -15.1 0 -3.6

TCTGCTGTTTTCGCTGGGTC 1577 SEQ ID NO: 998 -10.5 -27.4 80.1 -15.8 -1 -3.8

CCTCTCTTTTGGGCCCAGGA 1841 SEQ ID NO: 999 -10.5 -30.5 83.5 -17.9 0 -12.4

CGATAGAAAATAATTCAGGG 1990 SEQ ID NO: 1000 -10.5 -16.2 51.2 -4.9 -0.6 -3.9

CACTTCCCTCTAGTGCACTG 2524 SEQ ID NO: 1001 -10.5 -27 77 -15.1 -0.5 -10.6

TTTGATATGAAAACCACATT 3034 SEQ ID NO: 1002 -10.5 -16.9 52.7 -6.4 0 -3

TTTTGGCTTGTCAAACACAT 3207 SEQ ID NO: 1003 -10.5 -21 62.7 -7.6 -2.9 -7

ACTGCTGTTAATTTCCCAAA 3296 SEQ ID NO: 1004 -10.5 -22 63.5 -11.5 0 -4.8

AAGTAGTGTTATTACAATGA 3448 SEQ ID NO: 1005 -10.5 -17 55 -5.8 -0.5 -5.7

TTTTTGGAAATTTTGTTTTG 3579 SEQ ID NO: 1006 -10.5 -16.6 53.8 -6.1 0 -5.3

CGGAAGAGTACGCACGTACT 72 SEQ ID NO: 1007 -10.4 -23.9 66.2 -11.2 -1.9 -12.5

ATAAGAGTTTGGCCTTCTCT 622 SEQ ID NO: 1008 -10.4 -23.6 70.5 -12 -1 -9.6

CTGGTATTAACTTATTTTCT 652 SEQ ID NO: 1009 -10.4 -18.6 58.9 -7.7 -0.2 -3.6

GGTGTTTGCTTGTCCGAAAA 1143 SEQ ID NO: 1010 -10.4 -23.5 66.9 -13.1 0 -3.6

GCAAAGTCCAAGAGCCATCG 1172 SEQ ID NO: 1011 -10.4 -25 68.8 -13.9 -0.4 -3.9

TCCGTATCCTTCATAAAACT 1371 SEQ ID NO: 1012 -10.4 -21.3 61.7 -10.9 0 -2.6

ACATCAACAAGTTTTATCAA 1475 SEQ ID NO: 1013 -10.4 -17.1 54.3 -6.7 0 -3.6

TTGGCCCTTTCACACACACC

1534 SEQ ID NO: 1014 -10.4 -28.2 76.6 -17.8 0 -6.6 TTTGGCCCTTTCACACACAC

1535 SEQ ID NO: 1015 -10.4 -26.3 73.6 -15.9 0 -6.6 GTGTAACCAGCCGTCTTTGT

1605 SEQ ID NO: 1016 -10.4 -26.8 75.7 -16.4 0 -3.2

CTTAAATATGTGCTTTTTCC

1677 SEQ ID NO: 1017 -10.4 -19.7 60.3 -9.3 0 -3.6

ATAACTTAGCACATTTATAG

2364 SEQ ID NO: 1018 -10.4 -16.9 54.4 -6.5 0 -4.1

TTTTAAACTGAGGAAGTCTC

2386 SEQ ID NO: 1019 -10.4 -18.3 57.8 -7.1 -0.6 -5.6

119 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

ACACTTCCCTCTAGTGCACT 2525 SEQ ID NO:1020 -10.4 -27.2 77.8 -15.2 -1.4 -10.2

TTTTTAAATAACCCCTGAAA 2874 SEQ ID NO: 1021 -10.4 -18 54 -7.6 0 -4.5

TTTGGGGAAAAAGGCAAGTT 3070 SEQ ID NO:1022 -10.4 -19.9 59 -9.5 0 -4

GCATTATAAGAACATTTGCT 3170 SEQ ID NO: 1023 -10.4 -19 58.2 -8.1 -0.2 -5.3

AAAACAGCTGCTTTAAATGT 3368 SEQ ID NO: 1024 -10.4 -17.9 55 -6.8 0 -9.1

CATTGTTTTTGGAAATTTTG 3584 SEQ ID NO: 1025 -10.4 -17.1 54.4 -6.7 0 -5.3

AAGTAGTGCGGATCTTCGTG 222 SEQ ID NO: 1026 -10.3 -23.6 68.7 -12.7 -0.3 -5.1

TCGTATAATGTTGTGACATC 275 SEQ ID NO: 1027 -10.3 -19.5 60.2 -7.5 -1.7 -6.2

AGAGAGAGTTCAGCTTTGTT 584 SEQ ID NO: 1028 -10.3 -22.4 69.9 -11.5 -0.3 -4.7

TCTGGCCTCGTTCCACCAGT 712 SEQ ID NO: 1029 -10.3 -30.9 84.3 -18.5 -2.1 -7.2

CCATTGCTCCTTTGGGGTTG 856 SEQ ID NO: 1030 -10.3 -27.9 78 -16.7 -0.7 -5.7

CTGTTGCTTTCACAAAAGCT 907 SEQ ID NO: 1031 -10.3 -21.7 64.1 -8 -3.4 -8.5

GACTGTATTCTCTGTTGCTT 918 SEQ ID NO: 1032 -10.3 -23.4 71.7 -13.1 0 -3.7

AACATATGGGCGAGAGGCAA

971 SEQ ID NO: 1033 -10.3 -23.1 65.1 -11.2 -1.5 -8.6 AAACATATGGGCGAGAGGCA

972 SEQ ID NO: 1034 -10.3 -23.1 65.1 -11.2 -1.5 -8.6 TCCGATTTTAGCTCCATGAC

1020 SEQ ID NO: 1035 -10.3 -24.4 69.5 -14.1 0 -4.8

AACATCCGGTTCAGCAGTCT 1115 SEQ ID NO:1036 -10.3 -26 74.2 -15.7 0 -6

CTTCAGCGTGGTGTTTGCTT 1152 SEQ ID NO: 1037 -10.3 -26.5 77.1 -15.4 -0.6 -4.6

TGGCCCTTTCACACACACCT 1533 SEQ ID NO: 1038 -10.3 -29 78.1 -18.7 0 -6.6

AGTAGCCCTGAAATACATTT 1552 SEQ ID NO: 1039 -10.3 -21.6 63.2 -10.8 -0.2 -3.9

CTGGCCTTTTCGCCTTCATT 2032 SEQ ID NO: 1040 -10.3 -28.3 77.8 -16.2 -1.8 -7.2

TCTTCTTCACACTAAACCTT

2102 SEQ ID NO: 1041 -10.3 -21.4 63.9 -11.1 0 -0.9 TTCTTCTTCACACTAAACCT

2103 SEQ ID NO: 1042 -10.3 -21.4 63.9 -11.1 0 -0.9 TTGCTGTATTCAAAATTAAC

2181 SEQ ID NO:1043 -10.3 -16.1 52 -5.8 0 -3.6

ACTTCCCTCTAGTGCACTGT 2523 SEQ ID NO: 1044 -10.3 -27.5 79.5 -15.9 0 -10.6

ATGACAATTCTTTAGTGCAA 3432 SEQ ID NO: 1045 -10.3 -19.1 58.9 -8.8 0 -5.4

TGGTTTCCTTCATTGTTTTT 3594 SEQ ID NO:1046 -10.3 -22.8 69.4 -12.5 0 -3.2

CCACTGACTGCATGGAGAGG 181 SEQ ID NO: 1047 -10.2 -25.6 72.2 -14.6 -0.6 -5.6

GTATAATGTTGTGACATCAT 273 SEQ ID NO: 1048 -10.2 -19 59.5 -7.5 -1.2 -6.2

TCCTCCATCGCCTTCATGCT 752 SEQ ID NO: 1049 -10.2 -30.2 81.7 -20 0 -4.4

AGTGACCATTGCTCCTTTGG 861 SEQ ID NO: 1050 -10.2 -26.2 74.7 -16 0.6 -3.7

120 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo linding ation Duplex ture oligo oligo

AATCGCTCACTATGTTTCGG 883 SEQ ID NO: 1051 -10.2 -22.9 66.1 -12.7 0 -3.1

TGACTGTATTCTCTGTTGCT 919 SEQ ID NO: 1052 -10.2 -23.3 71.1 -13.1 0 -3.7

CCCTTTCACACACACCTCGC 1530 SEQ ID NO: 1053 -10.2 -29 77.2 -18.8 0 -2.7

TGTAACCAGCCGTCTTTGTC 1604 SEQ ID NO: 1054 -10.2 -26 74 -15.8 0 -3.2

AGCTTAAATATGTGCTTTTT 1679 SEQ ID NO: 1055 -10.2 -19.1 59.3 -8.3 -0.3 -4.3

ATATCTTCGAGGATAGCTTT 1907 SEQ ID NO: 1056 -10.2 -21.3 64.6 -9.9 -0.9 -9.9

GATAGAAAATAATTCAGGGT 1989 SEQ ID NO: 1057 -10.2 -16.6 53 -4.9 -1.4 -3.9

AGTTGTTCTTATTTTTAAAG 2548 SEQ ID NO: 1058 -10.2 -16.4 54.3 -6.2 0 -4.6

TTGGATCTGCCCTCCCGCTT 2731 SEQ ID NO: 1059 -10.2 -31.9 83.5 -21.1 -0.3 -6.3

GAGAATCCACGCGTTCTGAT

2794 SEQ ID NO: 1060 -10.2 -24.4 68.1 -13 -0.7 -10 AGAGAATCCACGCGTTCTGA

2795 SEQ ID NO: 1061 -10.2 -24.4 68.4 -13 -0.7 -10 AATAACCCCTGAAAAAGGAT

2868 SEQ ID NO: 1062 -10.2 -19 55.2 -7.6 -1.1 -3.8

TGTTGGCCTTTACACAGAGT 3007 SEQ ID NO: 1063 -10.2 -24.7 72.4 -14.5 0 -7.2

TTCGTATAATGTTGTGACAT 276 SEQ ID NO: 1064 -10.1 -19.2 59.1 -7.5 -1.5 -6

AATCACCCACTCAGGTCTAT 480 SEQ ID NO: 1065 -10.1 -24.9 71.5 -14.3 -0.2 -3.6

GTTTGGCCTTCTCTGGCTTG

616 SEQ ID NO: 1066 -10.1 -28 81.1 -16.3 -1.5 -7.2 AGTTTGGCCTTCTCTGGCTT

617 SEQ ID NO: 1067 -10.1 -28 81.7 -15.6 -2.3 -6.7 CACACCTCTGGCCTCGTTCC

718 SEQ ID NO: 1068 -10.1 -30.8 82.9 -20.7 0 -7.2

CACCCCACACCTCTGGCCTC 723 SEQ ID NO: 1069 -10.1 -33.2 85.9 -23.1 0 -7.2

GCTCCTGTCACCATCAGCCG 1298 SEQ ID NO: 1070 -10.1 -30.9 83.1 -20.3 -0.2 -5.1

CACATCAACAAGTTTTATCA 1476 SEQ ID NO: 1071 -10.1 -18.5 57.4 -8.4 0 -3.6

TCAAGGTGCCATTTGGTAAC 1645 SEQ ID NO: 1072 -10.1 -23.1 67.4 -13 0 -6.2

TGAGCAACAGGCTCACTTCG 1748 SEQ ID NO:1073 -10.1 -24.7 70.3 -10.6 -4 -10.3

TTTTGGGCCCAGGAACATAA 1835 SEQ ID NO: 1074 -10.1 -24.2 67.4 -12 0 -12.4

TCCTCTCTTTTGGGCCCAGG 1842 SEQ ID NO: 1075 -10.1 -30.3 84 -18.1 0 -12.4

CAGAAGGCCATTGTCGATAG 2004 SEQ ID NO:1076 -10.1 -23.1 66.3 -13 0 -6.9

TAGTGGAATAGAGGTCATCT 2080 SEQ ID NO: 1077 -10.1 -21.1 65.2 -11 0 -2.9

TTTAAACTGAGGAAGTCTCA 2385 SEQ ID NO: 1078 -10.1 -18.9 58.7 -7.1 -1.7 -6.9

CTCTTTAGAGCAGCAGACAG 2502 SEQ ID NO: 1079 -10.1 -23.2 69.9 -12.4 -0.4 -5.4

GATCTGCCCTCCCGCTTACT 2728 SEQ ID NO: 1080 -10.1 -31.4 82.7 -21.3 0 -4.8

CCCTGAAAAAGGATGGAGTC 2862 SEQ ID NO: 1081 -10.1 -21.9 62.7 -10.6 -1.1 -5.5

121 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GAAATGCTTGTCTTCACTAT 2909 SEQ ID NO: 1082 -10.1 -20.5 62.5 -10.4 0 -2.9

TTTTGATATGAAAACCACAT 3035 SEQ ID NO: 1083 -10.1 -16.9 52.7 -6.8 0 -3

TCCCAAATTAACTTTAAAAA 3283 SEQ ID NO: 1084 -10.1 -15 48.4 -4.9 0 -4.3

TTAATTTCCCAAATTAACTT 3289 SEQ ID NO: 1085 -10.1 -17.3 53.6 -4.9 -2.3 -6.9

CTGTTGTGCTTGTATATAAT 3409 SEQ ID NO: 1086 -10.1 -19.8 61.5 -9.7 0 -5.2

ATTTTGTTTTGGTTTATAAA

3570 SEQ ID NO: 1087 -10.1 -16.4 53.6 -6.3 0 -6.1 AATTTTGTTTTGGTTTATAA

3571 SEQ ID NO:1088 -10.1 -16.4 53.6 -6.3 0 -3.7 AAATTTTGTTTTGGTTTATA

3572 SEQ ID NO:1089 -10.1 -16.4 53.6 -6.3 0 -4.3 GAAATTTTGTTTTGGTTTAT

3573 SEQ ID NO: 1090 -10.1 -17.3 55.5 -7.2 0 -5.3 GAAATGCAGAAATATTTATT

3615 SEQ ID NO: 1091 -10.1 -14.6 48.5 -4.5 0 -6.7

CTTCGTATAATGTTGTGACA 277 SEQ ID NO: 1092 -10 -20.1 61.1 -9.3 -0.6 -4.2

ATTCATAGGGTTGGTCTGGT

352 SEQ ID NO: 1093 -10 -24.7 74.8 -14.7 0 -1.9 CATTCATAGGGTTGGTCTGG

353 SEQ ID NO: 1094 -10 -24.2 72.3 -14.2 0 -1.9 GGTCCTCCATCGCCTTCATG

754 SEQ ID NO: 1095 -10 -29.9 81.5 -19.2 -0.4 -4.9

GAGTGACCATTGCTCCTTTG 862 SEQ ID NO:1096 -10 -25.6 73.4 -15.1 -0.2 -3.6

CTCCTTGGAAAAATCCGATT 1033 SEQ ID NO: 1097 -10 -21.2 60.2 -10.3 -0.7 -5.3

CTTGAGGTCATCCATGAGCA 1062 SEQ ID NO: 1098 -10 -25.3 73.4 -14.6 -0.4 -4.5

CCGTATCCTTCATAAAACTG 1370 SEQ ID NO: 1099 -10 -20.9 60.4 -10.9 0 -2.6

CGTGGACAAACACCTGAGCA 1762 SEQ ID NO: 1100 -10 -24.4 67 -13.6 -0.6 -4.9

CCTGTTCAAATGGTTTCAGA 1951 SEQ ID NO: 1101 -10 -22.2 65.7 -12.2 0 -3.6

CCTTGATAGTGGAATAGAGG 2086 SEQ ID NO: 1102 -10 -21.1 63.2 -11.1 0 -2.9

TCTTCACACTAAACCTTGAT 2099 SEQ ID NO: 1103 -10 -20.6 61.5 -10.6 0 -2.7

ATTCAAAATTAACAACATGA 2174 SEQ ID NO: 1104 -10 -13.9 46.9 -3.9 0 -5.2

GCATTCCTATGAGAAGAACC 2242 SEQ ID NO: 1105 -10 -22.2 64.3 -11.5 -0.4 -3.9

AAGGCGGTGTTCTGTTTCCT 2265 SEQ ID NO: 1106 -10 -26.8 76.8 -16.8 0 -4

TTGGAAAGTGTGTATTACCA 2315 SEQ ID NO: 1107 -10 -20.5 61.8 -10.5 0 -4.3

TGGCCTTTACACAGAGTGAG 3004 SEQ ID NO: 1108 -10 -24 70.3 -13.1 -0.8 -8.5

TTGGGGAAAAAGGCAAGTTA 3069 SEQ ID NO: 1109 -10 -19.5 58.1 -9.5 0 -4

TAAGAACATTTGCTTATTAC 3164 SEQ ID NO: 1110 -10 -16.5 53.2 -6.5 0 -3.6

GGAGAAGTGAATCCCAGGAA 3257 SEQ ID NO: 1111 -10 -23 65.5 -13 0 -4.9

ATGGGCTTGCATTGTCCTGT 6 SEQ ID NO: 1112 -9.9 -27.5 78.8 -16.9 -0.5 -8

122 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCAAGGGCTCGTCGCTGTCA 241 SEQ ID NO: 1113 -9.9 -29.7 80.2 -18.8 -0.9 -5.1

ATAATGTTGTGACATCATCA 271 SEQ ID NO: 1114 -9.9 -19.2 59.6 -7.6 -1.7 -6.1

AACAAGGGCCATTATTTGAC 319 SEQ ID NO: 1115 -9.9 -21.2 62 -10.8 0 -8

TTCATAGGGTTGGTCTGGTT 351 SEQ ID NO: 1116 -9.9 -24.8 75.3 -14.9 0 -1.9

TCTGGGGCAGTCTTGAAGCC 434 SEQ ID NO: 1117 -9.9 -27.7 79.2 -16.9 -0.7 -6.1

GATCTGGGGCAGTCTTGAAG 436 SEQ ID NO: 1118 -9.9 -24.5 72.3 -14 -0.3 -4.5

ACTGATCTGGGGCAGTCTTG 439 SEQ ID NO: 1119 -9.9 -25.7 75.6 -14.7 -1 -4.9

TCTGTTGCTTTCACAAAAGC 908 SEQ ID NO: 1120 -9.9 -21.2 63.6 -8 -3.3 -8.2

CAGCATTACACACTCTACAA 999 SEQ ID NO: 1121 -9.9 -21.1 62.8 -11.2 0 -4.1

CTCGACTGTACTTTGTGGAA 1262 SEQ ID NO: 1122 -9.9 -22.3 65.7 -12.4 0 -4.8

CTTCAAGTAGCCCTGAAATA 1557 SEQ ID NO: 1123 -9.9 -21.9 63.6 -11.4 -0.3 -3.5

TTTGACATCCTTATTTCTGC 1887 SEQ ID NO: 1124 -9.9 -22.1 66.6 -12.2 0 -2.6

GAGGAAGTCTCAAATAACTT 2377 SEQ ID NO: 1125 -9.9 -18.1 56.5 -7.1 -1 -6

GTACTCTTTAGAGCAGCAGA 2505 SEQ ID NO: 1126 -9.9 -23.4 71.3 -12.1 -1.3 -7

CTTATCTGCATGGTTCTGAG 2751 SEQ ID NO: 1127 -9.9 -22.9 69.2 -13 0 -5

CCGAGTCCAAGAGCATTCTG

2822 SEQ ID NO: 1128 -9.9 -25.5 71.4 -14.9 -0.4 -4.1 GTTCAGTGAAGATAAAGTAG

2982 SEQ ID NO: 1129 -9.9 -17.3 55.8 -6.9 0 -8

CAAAAACCAGAGAGAGTTCA 592 SEQ ID NO: 1130 -9.8 -19 57.4 -8.6 -0.3 -3.4

TATTAACTTATTTTCTACAC 648 SEQ ID NO: 1131 -9.8 -16.1 53.1 -6.3 0 -2.9

CATGACAACTATGATTTTAA 675 SEQ ID NO: 1132 -9.8 -16.2 52 -6.4 0.8 -5.2

GTCTTGGAACCACGGGGAAG 1099 SEQ ID NO: 1133 -9.8 -25.1 69.5 -14.5 -0.6 -6.5

GTGGAAGATCAGCCGGTCCC 1248 SEQ ID NO: 1134 -9.8 -29.4 79.5 -19.1 -0.2 -7.4

AGCCGGACTCTTCCGCCCAG 1283 SEQ ID NO: 1135 -9.8 -32.6 83.4 -19.9 -2.9 -9.2

GCCCCAACATGGCCTGCGGT 1439 SEQ ID NO: 1136 -9.8 -33.6 84.2 -22.8 -0.9 -7.8

CAAATTGCACGGCATCGGGG 1458 SEQ ID NO: 1137 -9.8 -25.4 68.1 -14.6 -0.9 -7

CCAGGAACATAATGTCTCAA 1827 SEQ ID NO: 1138 -9.8 -20.6 60.8 -9.9 -0.8 -5

ATCTTCGAGGATAGCTTTTT 1905 SEQ ID NO: 1139 -9.8 -21.8 65.9 -11.5 0 -7.8

GCCTTTTCGCCTTCATTGTT 2029 SEQ ID NO: 1140 -9.8 -27.5 77.2 -17.7 0 -2.7

TAACCCCTTGATTAGAAAAG 2434 SEQ ID NO: 1141 -9.8 -19.1 56.5 -9.3 0 -2.5

GGGAACACTTCCCTCTAGTG 2529 SEQ ID NO:1142 -9.8 -25.9 73.8 -12.8 -3.3 -11.3

ACCGAGTCCAAGAGCATTCT

2823 SEQ ID NO: 1143 -9.8 -25.7 72.1 -15.4 -0.2 -4.1

123 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TTTTGGGGAAAAAGGCAAGT

3071 SEQ ID NO: 1144 -9.8 -19.9 59 -9.5 -0.3 -5.2 TTTGGCTTGTCAAACACATT

3206 SEQ ID NO: 1145 -9.8 -21 62.7 -8.6 -2.6 -7.2 GGCAAAGACTCACAATAAAG

3319 SEQ ID NO: 1146 -9.8 -17.6 54.1 -7.8 0 -4 TGGCAAAGACTCACAATAAA

3320 SEQ ID NO: 1147 -9.8 -17.6 53.9 -7.8 0 -4 GTTTCCTTCATTGTTTTTGG

3592 SEQ ID NO: 1148 -9.8 -22.8 69.4 -13 0 -2.9 TTGACACCTGTATTCCCCTC

304 SEQ ID NO: 1149 -9.7 -27.4 76.1 -17.7 0 -3.6 AAGTCCAAGAGCCATCGCTT

1169 SEQ ID NO: 1150 -9.7 -26 72.1 -14.8 -1.4 -4.4 ACGGCATCGGGGCCCCAACA

1450 SEQ ID NO: 1151 -9.7 -32.2 79.9 -19.4 -1.6 -14.4 CCACATCAACAAGTTTTATC

1477 SEQ ID NO: 1152 -9.7 -19.8 60 -10.1 0 -3.6 TCCACATCAACAAGTTTTAT

1478 SEQ ID NO: 1153 -9.7 -19.8 60 -10.1 0 -3.6 CCAGCTTAAATATGTGCTTT

1681 SEQ ID NO: 1154 -9.7 -21.6 63.7 -11.2 -0.4 -4.5 TGCCAGCTTAAATATGTGCT

1683 SEQ ID NO: 1155 -9.7 -23.2 66.9 -12.8 -0.4 -4.5 CCTGCAGGCTTTCTCCGTGG

1777 SEQ ID NO: 1156 -9.7 -30.4 82.9 -19.3 -0.2 -10.8 TTGGGCCCAGGAACATAATG

1833 SEQ ID NO: 1157 -9.7 -24 66.6 -12.2 0 -12.4 CATGGTCTGCAACATGAGGT

2291 SEQ ID NO: 1158 -9.7 -24.1 70.1 -13.2 -1.1 -7.6 TGTACTCTTTAGAGCAGCAG

2506 SEQ ID NO: 1159 -9.7 -22.8 69.7 -11.7 -1.3 -7 ACTGTACTCTTTAGAGCAGC

2508 SEQ ID NO: 1160 -9.7 -23.2 70.9 -11.7 -1.8 -8 ATCTGCCCTCCCGCTTACTG

2727 SEQ ID NO: 1161 -9.7 -30.8 81.3 -21.1 0 -3.2 CCTTATCTGCATGGTTCTGA

2752 SEQ ID NO: 1162 -9.7 -24.9 72.8 -15.2 0 -5 AGATTTTTAAATAACCCCTG

2877 SEQ ID NO: 1163 -9.7 -19.4 57.5 -9.1 -0.3 -4.2 GTGGCAAAGACTCACAATAA

3321 SEQ ID NO: 1164 -9.7 -19.5 58.4 -9.1 -0.5 -4 TGCTTTAAATGTACAAATGA

3360 SEQ ID NO: 1165 -9.7 -16.2 51.8 -6.5 0 -6.8 AATGACAATTCTTTAGTGCA

3433 SEQ ID NO: 1166 -9.7 -19.1 58.9 -9.4 0 -5.2 CACGTACTGTCGGAAGTCAA

60 SEQ ID NO: 1167 -9.6 -22.8 65.4 -12.7 -0.2 -5.5 TCCACCAGTTCACTGCCGTA

701 SEQ ID NO: 1168 -9.6 -29 79.1 -19.4 0.4 -5.9 TCAAACATATGGGCGAGAGG

974 SEQ ID NO: 1169 -9.6 -21.7 62.6 -12.1 0 -5.8 CATTACACACTCTACAACTC

996 SEQ ID NO: 1170 -9.6 -20.1 61.2 -10.5 0 -1.1 CATCAACAAGTTTTATCAAA

1474 SEQ ID NO: 1171 -9.6 -16.2 52 -6.6 0 -3.6 TTTTAAATAACCCCTGAAAA

2873 SEQ ID NO: 1172 -9.6 -17.2 52.2 -7.6 0 -4.5 GTTTTGGTTTATAAAACATA

3565 SEQ ID NO: 1173 -9.6 -16 52.2 -4.3 -2.1 -4.4 GTCAACCAGCTCTGGCATTC

45 SEQ ID NO: 1174 -9.5 -26.7 76.9 -15.6 -1.6 -7.7

124 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTTGGGTCTCGTGGCGTACC 141 SEQ ID NO: 1175 -9.5 -28.4 79 -17.8 -1 -6.2

ACCCGCCACTTCCACTGACT 192 SEQ ID NO: 1176 -9.5 -30.6 79.4 -21.1 0 -2.6

CATTATTTGACACCTGTATT 310 SEQ ID NO: 1177 -9.5 -20.3 61.4 -10.8 0 -3.6

GCTTCATTTCCAAGGGTATC 548 SEQ ID NO: 1178 -9.5 -24.2 71.6 -14.7 0 -3.6

AATAAGAGTTTGGCCTTCTC 623 SEQ ID NO: 1179 -9.5 -22 66.1 -12 0 -7.7

TTCGGTGAGTGACCATTGCT 868 SEQ ID NO: 1180 -9.5 -25.8 73.3 -14.6 -1.7 -5.3

ACAATCGCTCACTATGTTTC 885 SEQ ID NO: 1181 -9.5 -21.8 65.1 -12.3 0 -3.1

TGTATTCTCTGTTGCTTTCA 915 SEQ ID NO: 1182 -9.5 -22.9 70.9 -13.4 0 -3.6

GTATCATCTGGGCAAGGATT 938 SEQ ID NO: 1183 -9.5 -23.4 69.3 -13.9 0 -4.2

CAGCGTGGTGTTTGCTTGTC 1149 SEQ ID NO: 1184 -9.5 -26.7 78.1 -16.4 -0.6 -4.6

TTCAGCGTGGTGTTTGCTTG 1151 SEQ ID NO: 1185 -9.5 -25.6 74.9 -15.3 -0.6 -4.6

TGTCACCATCAGCCGGACTC 1293 SEQ ID NO: 1186 -9.5 -28.2 77.9 -17.9 -0.6 -6.7

AATACATTTGGCCCTTTCAC 1541 SEQ ID NO: 1187 -9.5 -23.5 67.3 -14 0 -6.6

GTCCAAAGCTTCTGCTGTTT 1587 SEQ ID NO: 1188 -9.5 -25.1 73.2 -13.9 -1.7 -6.6

TTTCTTCTTCACACTAAACC 2104 SEQ ID NO: 1189 -9.5 -20.6 62.3 -11.1 0 -1.7

GATTAGAAAAGCAGGGAGAC 2425 SEQ ID NO: 1190 -9.5 -19.2 58.5 -9.7 0 -4.1

GGATGGAGTCGGGGAATCAG 2852 SEQ ID Nθ:1191 -9.5 -24.6 70.3 -14.6 -0.2 -4.4

AAATAACCCCTGAAAAAGGA 2869 SEQ ID NO:1192 -9.5 -18.3 53.7 -7.6 -1.1 -4.1

CTTTTGATATGAAAACCACA 3036 SEQ ID NO: 1193 -9.5 -17.8 54.5 -8.3 0 -3

TGCCTGAGAGTTTATTTTTT 3087 SEQ ID NO: 1194 -9.5 -21.5 65.6 -12 0 -3

AGCATTATAAGAACATTTGC 3171 SEQ ID NO: 1195 -9.5 -18.1 56.4 -8.1 -0.2 -5.3

ATTTTGGCTTGTCAAACACA 3208 SEQ ID NO: 1196 -9.5 -21 62.7 -8.6 -2.9 -7.3

ATAAAACATAGAAATAGCCA 3555 SEQ ID NO: 1197 -9.5 -15.6 49.9 -6.1 0 -3.2

TTATTTTGGTTTCCTTCATT

3600 SEQ ID NO:1198 -9.5 -21.3 65.5 -11.8 0 -3.2 TTTATTTTGGTTTCCTTCAT

3601 SEQ ID NO: 1199 -9.5 -21.3 65.5 -11.8 0 -3.2 ATTTATTTTGGTTTCCTTCA

3602 SEQ ID NO: 1200 -9.5 -21.3 65.5 -11.8 0 -3.2 CTCGTCGCTGTCAAGTAGTG

234 SEQ ID NO: 1201 -9.4 -24.9 72.5 -15.5 0 -3.3

TTCATTTCCAAGGGTATCAT 546 SEQ ID NO: 1202 -9.4 -22.2 66.4 -12.8 0 -3.6

TTGACTGTATTCTCTGTTGC 920 SEQ ID NO:1203 -9.4 -22.5 69.4 -13.1 0 -3.3

AGTATCATCTGGGCAAGGAT 939 SEQ ID NO: 1204 -9.4 -23.3 69.2 -13.9 0 -4.1

CTCCATGACACAGCATTACA 1009 SEQ ID NO: 1205 -9.4 -23.6 67.9 -14.2 0 -4.5

125 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

Dsition oligo binding ation Duplex ture oligo oligo ATATCTCCTTGGAAAAATCC

1037 SEQ ID NO: 1206 -9.4 -19.8 58.9 -10.4 0 -4.4 CGGTTCAGCAGTCTTGGAAC

1109 SEQ ID NO: 1207 -9.4 -24.8 72 -14.3 -1 -5.4 GTTTTCGCTGGGTCCTTCAA

1571 SEQ ID NO: 1208 -9.4 -26.8 76.4 -17.4 0 -3.6 TGTCCAAAGCTTCTGCTGTT

1588 SEQ ID NO: 1209 -9.4 -25 72.7 -13.9 -1.7 -7 TCATTGTTGGAGTCAGAAGG

2017 SEQ ID NO: 1210 -9.4 -21.7 66.3 -12.3 0 -4.7 AACCCCTTGATTAGAAAAGC

2433 SEQ ID NO: 1211 -9.4 -21.2 60.6 -11.8 0 -2.8 TTCTGCCATGAAAGAGAATC

2807 SEQ ID NO: 1212 -9.4 -20 60 -10.6 0 -5.7 AATGCTTGCCTGAGAGTTTA

3093 SEQ ID NO: 1213 -9.4 -23.1 68 -13.7 0 -3.9 TACTGTCCATTTCAATAAGT

3147 SEQ ID NO: 1214 -9.4 -19.9 61 -10.5 0 -3 TTCCTTCATTGTTTTTGGAA

3590 SEQ ID NO: 1215 -9.4 -21.4 64.7 -11.3 -0.4 -4.6 TATTTTGGTTTCCTTCATTG

3599 SEQ ID NO: 1216 -9.4 -21.2 65 -11.8 0 -3.2 CAACCAGCTCTGGCATTCGA

43 SEQ ID NO: 1217 -9.3 -26.5 72.9 -15.6 -1.6 -8.6 AGTAGTGCGGATCTTCGTGC

221 SEQ ID NO: 1218 -9.3 -26.1 75.5 -15.9 -0.8 -6.6 ATTTGACACCTGTATTCCCC

306 SEQ ID NO: 1219 -9.3 -26.2 72.9 -16.9 0 -3 GCCTAAACAAGGGCCATTAT

324 SEQ ID NO: 1220 -9.3 -23.9 66.4 -13.2 -1.3 -8 TAATAAGAGTTTGGCCTTCT

624 SEQ ID NO: 1221 -9.3 -21.3 64 -12 0 -7.2 CTAATAAGAGTTTGGCCTTC

625 SEQ ID NO: 1222 -9.3 -21.3 64 -12 0 -7.2 TCTAATAAGAGTTTGGCCTT

626 SEQ ID NO: 1223 -9.3 -21.3 64 -12 0 -7.2 ACCTCTGGCCTCGTTCCACC

715 SEQ ID NO: 1224 -9.3 -32.1 85.3 -22.8 0 -7.2 TTGGCTCTTCCCAGGTCCTC

767 SEQ ID NO: 1225 -9.3 -30.6 86.7 -20.8 -0.2 -4.4 GTGACCATTGCTCCTTTGGG

860 SEQ ID NO: 1226 -9.3 -27.4 77 -17.2 -0.7 -4.3 GTTGCTTTCACAAAAGCTGA

905 SEQ ID NO: 1227 -9.3 -21.4 63.5 -8 -4.1 -9.3 CTTGGAAAAATCCGATTTTA

1030 SEQ ID NO: 1228 -9.3 -17.8 54 -7.2 -1.2 -9.3 GGGGCCCCAACATGGCCTGC

1442 SEQ ID NO: 1229 -9.3 -34 86.2 -20.8 -3.9 -14.2 CTCGCCCTCGCCCTCGGCAG

1515 SEQ ID NO: 1230 -9.3 -35.6 87.7 -24.1 -2.2 -7.2 TACATTTGGCCCTTTCACAC

1539 SEQ ID NO: 1231 -9.3 -25.1 71.3 -15.8 0 -6.6 TTCTGCTGTTTTCGCTGGGT

1578 SEQ ID NO: 1232 -9.3 -27.1 78.6 -16.7 -1 -3.8 AAACACCTGAGCAACAGGCT

1755 SEQ ID NO: 1233 -9.3 -23.8 66.6 -12.2 -2.3 -9.6 TGGGCCCAGGAACATAATGT

1832 SEQ ID NO: 1234 -9.3 -25.1 69.3 -13.9 0 -11.9 CATATCTTCGAGGATAGCTT

1908 SEQ ID NO: 1235 -9.3 -21.9 65.5 -11.4 -0.9 -9.9 GATAGTGGAATAGAGGTCAT

2082 SEQ ID NO: 1236 -9.3 -20.4 63 -11.1 0 -2.7

126 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TGATAGTGGAATAGAGGTCA 2083 SEQ ID NO: 1237 -9.3 -20.4 62.9 -11.1 0 -2.7

CTTCACACTAAACCTTGATA 2098 SEQ ID NO: 1238 -9.3 -19.9 59.6 -10.6 0 -2.7

CTGTAAGGCGGTGTTCTGTT 2269 SEQ ID NO:1239 -9.3 -25.2 73.7 -15.9 0 -4.3

ACATGGTCTGCAACATGAGG 2292 SEQ ID NO: 1240 -9.3 -23.1 67.4 -11.8 -2 -9.1

AAAGTCCTAACCCCTTGATT 2441 SEQ ID NO: 1241 -9.3 -24 66.7 -14.7 0 -2.7

TGATATGAAAACCACATTAA 3032 SEQ ID NO: 1242 -9.3 -15.7 50.1 -6.4 0 -3

ATATACTCCCTTAATAGCTT 3119 SEQ ID NO: 1243 -9.3 -21.4 63.7 -12.1 0 -4.6

TCACAGACCCCAAAACAGCT 3379 SEQ ID NO: 1244 -9.3 -25 68 -15.7 0 -4.3

TTTTGGTTTATAAAACATAG 3564 SEQ ID NO: 1245 -9.3 -14.8 49.6 -4.3 -1.1 -4.4

TATTTGACACCTGTATTCCC 307 SEQ ID NO: 1246 -9.2 -23.9 68.8 -14.7 0 -3.6

ATTATTTGACACCTGTATTC 309 SEQ ID NO: 1247 -9.2 -20 61.6 -10.8 0 -3.6

AAAGCCATTCATAGGGTTGG 358 SEQ ID NO: 1248 -9.2 -22.9 66.5 -12.1 -1.5 -4.9

ATTCGGTCAAACATCCGGTT 1124 SEQ ID NO: 1249 -9.2 -24 67.1 -13.1 -1.7 -6.6

CTGTACTTTGTGGAAGATCA 1257 SEQ ID NO: 1250 -9.2 -21.1 64.2 -11.9 0 -5.4

CTTCATAAAACTGACAGCCC 1363 SEQ ID NO: 1251 -9.2 -22.1 63.1 -12.9 0 -4.1

TCTGTCCGTATCCTTCATAA 1375 SEQ ID NO: 1252 -9.2 -24.1 69.8 -14.9 0 -2.6

GCTGGGTCCTTCAAGTAGCC 1565 SEQ ID NO: 1253 -9.2 -28.8 82.1 -19.6 0 -4.1

GCTTAAATATGTGCTTTTTC 1678 SEQ ID NO: 1254 -9.2 -19.5 60.5 -10.3 0 -3.6

TGTCGATAGAAAATAATTCA 1993 SEQ ID NO: 1255 -9.2 -15.4 50 -4.7 -1.4 -8.7

CTTGATAGTGGAATAGAGGT 2085 SEQ ID NO: 1256 -9.2 -20.3 62.5 -11.1 0 -1.5

ACGAACGCTTCCTTCCCTAC 2203 SEQ ID NO: 1257 -9.2 -27.3 72.7 -18.1 0 -4.6

TGAGGAAGTCTCAAATAACT 2378 SEQ ID NO: 1258 -9.2 -18 56.1 -7.1 -1.7 -4.8

TTAAACTGAGGAAGTCTCAA 2384 SEQ ID NO: 1259 -9.2 -18.1 56.5 -7.1 -1.8 -5.5

TTTTTAAACTGAGGAAGTCT 2387 SEQ ID NO: 1260 -9.2 -18 56.8 -8.1 -0.5 -4.4

AGTTGGATCTGCCCTCCCGC 2733 SEQ ID NO: 1261 -9.2 -32.1 85.1 -22.3 -0.3 -5.2

CGCGTTCTGATGAGCACCCA 2785 SEQ ID NO: 1262 -9.2 -28.6 75.8 -18.7 -0.4 -7.5

TTGGCCTTTACACAGAGTGA 3005 SEQ ID NO: 1263 -9.2 -24.1 70.4 -14 -0.8 -8.5

GGGGAAAAAGGCAAGTTAAT

3067 SEQ ID NO: 1264 -9.2 -18.7 56.1 -9.5 0 -4 TGGGGAAAAAGGCAAGTTAA

3068 SEQ ID NO: 1265 -9.2 -18.7 56.1 -9.5 0 -4 GTTAATTTCCCAAATTAACT

3290 SEQ ID NO: 1266 -9.2 -18.4 56 -4.9 -4.3 -10.9

GCAAAGACTCACAATAAAGT 3318 SEQ ID NO:1267 -9.2 -17.6 54.4 -8.4 0 -3.4

127 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo άnding ation Duplex ture oligo oligo

GCAAACATTCAAAACCCCAA 3526 SEQ ID NO: 1268 -9.2 -21.3 59.1 -12.1 0 -3.4

TGTTTTGGTTTATAAAACAT 3566 SEQ ID NO:1269 -9.2 -16.3 52.7 -4.3 -2.8 -8.2

CCTTCATTGTTTTTGGAAAT 3588 SEQ ID NO: 1270 -9.2 -20.2 60.8 -11 0 -3.5

TCAACCAGCTCTGGCATTCG 44 SEQ ID NO: 1271 -9.1 -26.3 73.2 -15.6 -1.6 -8.6

AGTCAACCAGCTCTGGCATT 46 SEQ ID NO: 1272 -9.1 -26.3 75.4 -15.6 -1.6 -8.6

CGTGTTGGTCGGAAGAGTAC 81 SEQ ID NO: 1273 -9.1 -23.7 68.7 -13.8 -0.6 -4.8

TCGTCGCTGTCAAGTAGTGC 233 SEQ ID NO: 1274 -9.1 -25.8 75 -16.7 0 -4.1

AGAAATACACCAAGGGCTCG 250 SEQ ID NO: 1275 -9.1 -22.3 62.9 -13.2 0 -4.5

TGAGTGACCATTGCTCCTTT 863 SEQ ID NO: 1276 -9.1 -25.6 73.4 -15.5 -0.9 -3.8

ACACAGCATTACACACTCTA 1002 SEQ ID NO: 1277 -9.1 -22 65.5 -12.9 0 -3.3

GTCCAAGAGCCATCGCTTCA 1167 SEQ ID NO: 1278 -9.1 -27.8 76.8 -17.2 -1.4 -4.6

AGGAACATAATGTCTCAACA

1825 SEQ ID NO: 1279 -9.1 -18.8 57.7 -8.8 -0.8 -5.2 CAGGAACATAATGTCTCAAC

1826 SEQ ID NO: 1280 -9.1 -18.8 57.7 -8.8 -0.8 -5 CTCTGGCCTTTTCGCCTTCA

2034 SEQ ID NO: 1281 -9.1 -29.5 81.2 -18.6 -1.8 -7.2

ATAGTGGAATAGAGGTCATC

2081 SEQ ID NO: 1282 -9.1 -20.2 63.1 -11.1 0 -2.7

TTCTTCACACTAAACCTTGA

2100 SEQ ID NO: 1283 -9.1 -20.7 61.8 -11.6 0 -2.6

CGGTGTTCTGTTTCCTCTAG

2261 SEQ ID NO: 1284 -9.1 -25.5 75.4 -16.4 0 -3.4 GCGGTGTTCTGTTTCCTCTA

2262 SEQ ID NO: 1285 -9.1 -27.3 79.8 -18.2 0 -3.4 AAAGTGTGTATTACCATAAA

2311 SEQ ID NO: 1286 -9.1 -16.9 53.4 -7.8 0 -3.6

CTGAGGAAGTCTCAAATAAC

2379 SEQ ID NO: 1287 -9.1 -18 56.1 -7.1 -1.8 -5 ACTGAGGAAGTCTCAAATAA

2380 SEQ ID NO:1288 -9.1 -18 56.1 -7.1 -1.8 -5 CTCTTTCTTGAAATGCTTGT

2918 SEQ ID NO: 1289 -9.1 -21 63.8 -11.2 -0.5 -5.2

CAATAAGTACTCAAGTATAT 3135 SEQ ID NO: 1290 -9.1 -16 52.3 -6.9 0 -5.7

AAGAACATTTGCTTATTACT 3163 SEQ ID NO: 1291 -9.1 -17.7 55.7 -8.6 0 -3.6

TTGGCTTGTCAAACACATTT 3205 SEQ ID NO: 1292 -9.1 -21 62.7 -10.3 -1.6 -7.2

AACTGCTGTTAATTTCCCAA 3297 SEQ ID NO: 1293 -9.1 -22 63.5 -12.4 -0.1 -6.8

GACCCCAAAACAGCTGCTTT 3374 SEQ ID NO: 1294 -9.1 -25.9 69.8 -16.1 0 -8.9

TATAATGTTGTGACATCATC 272 SEQ ID NO: 1295 -9 -18.2 57.7 -7.5 -1.7 -7

AAACAAGGGCCATTATTTGA 320 SEQ ID NO: 1296 -9 -20.3 59.6 -10.8 0 -7.5

CTAAACAAGGGCCATTATTT 322 SEQ ID NO: 1297 -9 -20.3 59.7 -10.8 0 -7.6

AATAATCACCCACTCAGGTC 483 SEQ ID NO: 1298 -9 -23.3 67.3 -13.8 -0.2 -3.6

128 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTTGGCCTTCTCTGGCTTGT 615 SEQ ID NO: 1299 -9 -28 81.1 -16.7 -2.3 -7.2

TCTGGGCAAGGATTGACTGT 932 SEQ ID NO: 1300 -9 -24.3 70.8 -14 -1.2 -6.1

AAGCTCTGCTTCTTTCCTCT 1197 SEQ ID NO: 1301 -9 -26.2 77.4 -15.8 -1.3 -6.3

GTCACCATCAGCCGGACTCT 1292 SEQ ID NO: 1302 -9 -29.1 80 -20.1 0 -6.7

AGACACCGGGGCGGCTCCTG 1311 SEQ ID NO: 1303 -9 -31.9 82.2 -21.6 -1.1 -9.6

CTGTCTGTCCGTATCCTTCA 1378 SEQ ID NO: 1304 -9 -27.2 78.2 -18.2 0 -2.6

TCAAATTGCACGGCATCGGG 1459 SEQ ID NO: 1305 -9 -24.6 67.1 -14.6 -0.9 -7.3

TCAACAAGTTTTATCAAATT

1472 SEQ ID NO: 1306 -9 -15.6 51.1 -6.6 0 -3.6 AGCCGTCTTTGTCCAAAGCT

1597 SEQ ID NO: 1307 -9 -26.9 74.8 -17 -0.7 -8.4

GGACAAACACCTGAGCAACA 1759 SEQ ID NO: 1308 -9 -22.6 63.6 -13.6 0 -4.1

CCGTGGACAAACACCTGAGC 1763 SEQ ID NO: 1309 -9 -25.7 69.3 -15.9 -0.6 -3.8

AGAAAATAATTCAGGGTGCA 1986 SEQ ID NO: 1310 -9 -18.8 57.3 -8.3 -1.4 -7.1

TCGATAGAAAATAATTCAGG 1991 SEQ ID NO: 1311 -9 -15.4 49.9 -4.9 -1.4 -6.1

ACCTTGATAGTGGAATAGAG 2087 SEQ ID NO: 1312 -9 -20.1 61.2 -11.1 0 -3.3

TGTATTCAAAATTAACAACA 2177 SEQ ID NO: 1313 -9 -14.2 47.6 -5.2 0 -4.2

CACTTGCTGTATTCAAAATT 2184 SEQ ID NO: 1314 -9 -18.7 57.4 -9.7 0 -2.9

TAAGGCGGTGTTCTGTTTCC 2266 SEQ ID NO: 1315 -9 -25.6 74.2 -16.6 0 -4

CTGCAACATGAGGTGACTGT 2285 SEQ ID NO: 1316 -9 -23.5 68.5 -13.6 -0.7 -5.9

ATTACCATAAACATGGTCTG 2302 SEQ ID NO: 1317 -9 -19.6 59 -8.5 -2.1 -7.8

CCCAAATTAACTTTAAAAAA 3282 SEQ ID NO: 1318 -9 -13.9 46.1 -4.9 0 -4.3

CAGCTCTGGCATTCGAAAAT 39 SEQ ID NO: 1319 -8.9 -22.2 63.5 -11.7 -1.6 -9.5

ACTGTCGGAAGTCAACCAGC 55 SEQ ID NO: 1320 -8.9 -24.9 70.5 -15.5 -0.2 -3.9

CAAGGGCCATTATTTGACAC 317 SEQ ID NO: 1321 -8.9 -22.6 65.2 -13.2 0 -8

GCAGTCTTGAAGCCCTTCTG 428 SEQ ID NO: 1322 -8.9 -27.1 77.2 -17.5 -0.4 -6.7

AACTTATTTTCTACACCCTC 644 SEQ ID NO: 1323 -8.9 -21.9 65 -13 0 -0.9

CACCTCTGGCCTCGTTCCAC 716 SEQ ID NO: 1324 -8.9 -30.8 82.9 -21.4 -0.2 -7.2

AGTCCAAGAGCCATCGCTTC 1168 SEQ ID NO: 1325 -8.9 -27.1 76.1 -16.7 -1.4 -4.2

CACCGGGGCGGCTCCTGTCA 1308 SEQ ID NO: 1326 -8.9 -33.4 86 -22.8 -1.7 -9.6

ATCAACAAGTTTTATCAAAT

1473 SEQ ID NO:1327 -8.9 -15.5 50.8 -6.6 0 -3.6 TTCATTTCTTCCACATCAAC

1487 SEQ ID NO: 1328 -8.9 -21.4 64.4 -12.5 0 -1

TTGACATCCTTATTTCTGCA 1886 SEQ ID NO:1329 -8.9 -22.7 67.4 -13.8 0 -4.7

129 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GCCATCAGCAGGAGAAGAGA

2152 SEQ ID NO: 1330 -8.9 -25 71 .8 -15.3 -0.6 -4.1 CTAGCATTCCTATGAGAAGA

2245 SEQ ID NO: 1331 -8.9 -21.3 63 .8 -11.7 -0.4 -4.1 AGGTGACTGTAAGGCGGTGT

2275 SEQ ID NO: 1332 -8.9 -25.7 74 2 -16.3 -0.2 -5.2 AAGGGAACACTTCCCTCTAG

2531 SEQ ID NO: 1333 -8.9 -24 68 6 -10.6 -4.5 -12.4 AAGAGAATCCACGCGTTCTG

2796 SEQ ID NO: 1334 -8.9 -23.1 65 1 -13 -0.7 -10 TAAATAACCCCTGAAAAAGG

2870 SEQ ID NO: 1335 -8.9 -17.4 52 1 -7.6 -0.7 -3.7 TACAATGACAATTCTTTAGT

3436 SEQ ID NO: 1336 -8.9 -17.2 54 9 -8.3 0 -3.1 CCAAGGTGACAAATTATTGA

3510 SEQ ID NO: 1337 -8.9 -19 57 1 -8.9 -1.1 -4.9 TAATGTTGTGACATCATCAT

270 SEQ ID NO: 1338 -8.8 -19.2 59 6 -8.7 -1.7 -6.2 TTATTTGACACCTGTATTCC

308 SEQ ID NO: 1339 -8.8 -22 65 5 -13.2 0 -3.6 GGTCTGGTTTCCGAGAGCCT

340 SEQ ID NO: 1340 -8.8 -29.4 82 4 -19.7 -0.7 -5.1 ACTGCAAGATCTTCAGGTGC

809 SEQ ID NO: 1341 -8.8 -24.2 71 7 -13.6 -0.5 -11.8 GTTTGCTTGTCCGAAAATTC

1140 SEQ ID NO: 1342 -8.8 -21.6 63 3 -12.8 0 -3.6 CGACTGTACTTTGTGGAAGA

1260 SEQ ID NO: 1343 -8.8 -21.6 63 8 -11.9 -0.7 -5.5 GGGGCGGCTCCTGTCACCAT

1304 SEQ ID NO: 1344 -8.8 -32.6 86 7 -22.9 -0.6 -9.3 AGGGCTGCTCTGAGGAACGT

1343 SEQ ID NO: 1345 -8.8 -27 75 9 -18.2 0 -7.1 CTGTTTTCGCTGGGTCCTTC

1573 SEQ ID NO: 1346 -8.8 -27.7 79 8 -18.9 0 -3.6 TCCAAAGCTTCTGCTGTTTT

1586 SEQ ID NO: 1347 -8.8 -24 70 2 -13.9 -1.2 -7 TGCCATTTGGTAACCATTTT

1639 SEQ ID NO: 1348 -8.8 -23.3 66 8 -13.8 -0.4 -6.2 GTGGACAAACACCTGAGCAA

1761 SEQ ID NO: 1349 -8.8 -22.9 64 8 -13.6 -0.1 -4.3 CTTCCCTCTAGTGCACTGTA

2522 SEQ ID NO: 1350 -8.8 -27 78 3 -16.9 0 -10.6 TTTAAATAACCCCTGAAAAA

2872 SEQ ID NO: 1351 -8.8 -16.4 50 4 -7.6 0 -4 TTGCCTGAGAGTTTATTTTT

3088 SEQ ID NO: 1352 -8.8 -21.5 65 6 -12.7 0 -3 TCCCTTAATAGCTTTAAAGA

3113 SEQ ID NO: 1353 -8.8 -19.9 59 7 -10.6 0 -8.1 TGTCAAACACATTTCATAGA

3199 SEQ ID NO: 1354 -8.8 -18.3 57 1 -9.5 0 -3.6 TTGTCAAACACATTTCATAG

3200 SEQ ID NO: 1355 -8.8 -17.8 56 1 -8.5 -0.1 -3.7 AATCCCTGGAGAAGTGAATC

3264 SEQ ID NO: 1356 -8.8 -21.8 63 6 -13 0 -4.8 AGTAGTGTTATTACAATGAC

3447 SEQ ID NO: 1357 -8.8 -17.9 57 5 -8.6 -0.2 -5.7 GGTTTCCTTCATTGTTTTTG

3593 SEQ ID NO: 1358 -8.8 -22.8 69 4 -14 0 -2.5 GCTCTGGCATTCGAAAATAC

37 SEQ ID NO: 1359 -8.7 -21.4 62 2 -11.7 -0.8 -9.3 TTTGACACCTGTATTCCCCT

305 SEQ ID NO: 1360 -8.7 -27.1 74 8 -18.4 0 -3.6

130 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo AGGTCTATTTTGAGCAAAGA

468 SEQ ID NO: 1361 -8.7 -20 61.5 -11.3 0 -5.9 ACACCTCTGGCCTCGTTCCA

717 SEQ ID NO: 1362 -8.7 -30.8 82.9 -21.6 -0.1 -7.2 TTTCGGTGAGTGACCATTGC

869 SEQ ID NO: 1363 -8.7 -25 71.8 -14.6 -1.7 -5.2 TGTTGCTTTCACAAAAGCTG

906 SEQ ID NO: 1364 -8.7 -20.8 62.1 -8 -4.1 -9.2 GGATTGACTGTATTCTCTGT

923 SEQ ID NO: 1365 -8.7 -22.4 68.7 -13.7 0 -3.3 AAGTATCATCTGGGCAAGGA

940 SEQ ID NO: 1366 -8.7 -22.6 66.9 -13.9 0 -4 CATGACACAGCATTACACAC

1006 SEQ ID NO: 1367 -8.7 -21.4 63.1 -12.7 0 -4.1 GAGCAGCCTGATATCTCCTT

1047 SEQ ID NO: 1368 -8.7 -26.8 76.7 -18.1 0 -6.4 AAGAGCCATCGCTTCAGCGT

1163 SEQ ID NO: 1369 -8.7 -27.3 74.9 -16.7 -1.9 -9.9 TCTTCCACATCAACAAGTTT

1481 SEQ ID NO: 1370 -8.7 -21.4 63.9 -12.7 0 -3.6 TTCTTCCACATCAACAAGTT

1482 SEQ ID NO: 1371 -8.7 -21.4 63.9 -12.7 0 -3.5 TTTCTCCGTGGACAAACACC

1768 SEQ ID NO: 1372 -8.7 -24.3 67.6 -14.8 -0.6 -5.6 CTCACCATATCTTCGAGGAT

1913 SEQ ID NO: 1373 -8.7 -23.6 68.2 -14.4 0 -8 TTGATAGTGGAATAGAGGTC

2084 SEQ ID NO: 1374 -8.7 -19.8 62 -11.1 0 -1.8 GGTGTTCTGTTTCCTCTAGC

2260 SEQ ID NO: 1375 -8.7 -26.5 80.7 -17.8 0 -3.7 TGATTAGAAAAGCAGGGAGA

2426 SEQ ID NO: 1376 -8.7 -19 57.9 -10.3 5 -4.1 TGAGAAGGGACAGTAGCAGG

2615 SEQ ID NO: 1377 -8.7 -23 68.1 -14.3 0 -4.1 TTAAATAACCCCTGAAAAAG

2871 SEQ ID NO: 1378 -8.7 -16.3 50.3 -7.6 0 -2 CAGATTTTTAAATAACCCCT

2878 SEQ ID NO: 1379 -8.7 -20.1 58.7 -10.8 -0.3 -4.5 AATAAGTACTCAAGTATATA

3134 SEQ ID NO: 1380 -8.7 -15 50.4 -6.3 0 -6.2 ATTGTTTTTGGAAATTTTGT

3583 SEQ ID NO: 1381 -8.7 -17.6 56.1 -8.9 0 -5.3 TCCTTCATTGTTTTTGGAAA

3589 SEQ ID NO: 1382 -8.7 -20.6 62.2 -11.9 0 -3.8 GGGCTCGTCGCTGTCAAGTA

237 SEQ ID NO: 1383 -8.6 -27.9 78.6 -18.3 -0.9 -5.1 CCTCTGGCCTCGTTCCACCA

714 SEQ ID NO: 1384 -8.6 -32.6 85.6 -23.5 -0.2 -6.5 CCACCCCACACCTCTGGCCT

724 SEQ ID NO: 1385 -8.6 -34.8 87.3 -26.2 0 -7.2 TGAGCAGCCTGATATCTCCT

1048 SEQ ID NO: 1386 -8.6 -26.7 76.1 -18.1 0 -6.4 CGTGGTGTTTGCTTGTCCGA

1146 SEQ ID NO: 1387 -8.6 -27.6 76.9 -19 0 -3.6 TCTTGGAGGCAAAGTCCAAG

1180 SEQ ID NO: 1388 -8.6 -23.1 67 -10.8 -3.7 -10 TCAGCCGGACTCTTCCGCCC

1285 SEQ ID NO: 1389 -8.6 -33 84.8 -21.7 -2.7 -9.2 TTCCACATCAACAAGTTTTA

1479 SEQ ID NO: 1390 -8.6 -19.9 60.3 -11.3 0 -3.6 GCTGTTTTCGCTGGGTCCTT

1574 SEQ ID NO: 1391 -8.6 -29.1 82.5 -19.9 -0.3 -3.9

131 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTGTCCAAAGCTTCTGCTGT 1589 SEQ ID NO: 1392 -8.6 -25 72.7 -14.7 -1.7 -7

TAACCAGCCGTCTTTGTCCA 1602 SEQ ID NO: 1393 -8.6 -27.5 75.4 -18.9 0 -3.2

TCACCATATCTTCGAGGATA 1912 SEQ ID NO: 1394 -8.6 -22.4 65.7 -12.8 -0.7 -9.6

GTCATCTATCTGCGACCTGA 2067 SEQ ID NO: 1395 -8.6 -25.5 73.1 -16.9 0 -4.2

ACTAAACCTTGATAGTGGAA 2092 SEQ ID NO: 1396 -8.6 -19.2 58 -10.6 0 -3.4

TCCTATGAGAAGAACCCCGA 2238 SEQ ID NO: 1397 -8.6 -25 67.4 -16.4 0 -2.8

ACATGAGGTGACTGTAAGGC 2280 SEQ ID NO: 1398 -8.6 -22.8 67.8 -13.7 -0.2 -5.5

TTACCATAAACATGGTCTGC 2301 SEQ ID NO: 1399 -8.6 -21.4 63 -10.7 -2.1 -7.8

CTAGTGCACTGTACTCTTTA 2515 SEQ ID NO: 1400 -8.6 -22.6 69.2 -12.7 -0.2 -10.6

GACAGTAGCAGGGATTTAAA 2607 SEQ ID NO: 1401 -8.6 -20.4 61.7 -11.8 0 -4.6

ACTGTCCATTTCAATAAGTA 3146 SEQ ID NO: 1402 -8.6 -19.9 61 -11.3 0 -2.6

CTTATTACTGTCCATTTCAA 3152 SEQ ID NO: 1403 -8.6 -20.5 62.4 -11.9 0 -3

GTAGTGTTATTACAATGACA 3446 SEQ ID NO: 1404 -8.6 -18.6 58.7 -9.3 -0.5 -6.1

TGGCATTCGAAAATACCGGA 33 SEQ ID NO: 1405 -8.5 -22 61.1 -13 0 -7.9

TCTGGCATTCGAAAATACCG 35 SEQ ID NO: 1406 -8.5 -21.5 60.6 -13 0 -7.3

TCCACTGACTGCATGGAGAG 182 SEQ ID NO: 1407 -8.5 -24.8 71.2 -14.6 -1.7 -7.8

ACCAAGGGCTCGTCGCTGTC 242 SEQ ID NO: 1408 -8.5 -29.2 79.8 -19.7 -0.9 -5.1

GCTCTTCCCAGGTCCTCCAT 764 SEQ ID NO: 1409 -8.5 -32 88.3 -22.2 -1.2 -4.5

ATATGGGCGAGAGGCAAGAA 968 SEQ ID NO: 1410 -8.5 -22.8 64.9 -12.7 -1.5 -4

AACTCTCTCAAACATATGGG 981 SEQ ID NO: 1411 -8.5 -19.7 59.6 -11.2 0 -6.7

ATGACACAGCATTACACACT 1005 SEQ ID NO: 1412 -8.5 -21.6 63.8 -13.1 0 -4.1

TGGAACCACGGGGAAGACAG 1095 SEQ ID NO: 1413 -8.5 -24 66 -15.5 0.3 -5.6

CAAGAGCCATCGCTTCAGCG 1164 SEQ ID NO: 1414 -8.5 -26.8 72.8 -16.7 -1.6 -9.3

ACGTCAGCACAGTGGCAGAC 1327 SEQ ID NO: 1415 -8.5 -26.4 75.5 -16.6 -1.2 -9.1

GGAACATAATGTCTCAACAT 1824 SEQ ID NO: 1416 -8.5 -18.8 57.5 -8.8 -1.4 -6

TTTGGGCCCAGGAACATAAT 1834 SEQ ID NO: 1417 -8.5 -24.1 67.1 -13.5 0 -12.4

TTTCCTCTGAGCTTTCTTCT 2116 SEQ ID NO: 1418 -8.5 -25 75.5 -16.5 0 -5.7

CCCACTTTTTAAACTGAGGA 2392 SEQ ID NO: 1419 -8.5 -22 63.4 -13.5 0 -4.4

ATTAGAAAAGCAGGGAGACA 2424 SEQ ID NO: 1420 -8.5 -19.3 58.4 -10.8 0 -4.1

TGCCCTCCCGCTTACTGGAA 2724 SEQ ID NO: 1421 -8.5 -30.6 79.1 -22.1 0 -3.5

CTGAGTTGGATCTGCCCTCC 2736 SEQ ID NO: 1422 -8.5 -29 80.9 -19.8 -0.5 -5

132 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TTTTTGGGGAAAAAGGCAAG

3072 SEQ ID NO: 1423 -8.5 -18.8 56.5 -9.5 -0.6 -7.5 TATTTATTTTGGTTTCCTTC

3603 SEQ ID NO: 1424 -8.5 -20.3 63.6 -11.8 0 -3.2 TCATTTCCAAGGGTATCATA

545 SEQ ID NO: 1425 -8.4 -21.8 65.4 -13.4 0 -3.6 AGGTCCTCCATCGCCTTCAT

755 SEQ ID NO: 1426 -8.4 -29.9 82.1 -20.2 -1.2 -4.5 TGACCATTGCTCCTTTGGGG

859 SEQ ID NO: 1427 -8.4 -27.4 76.1 -18.1 -0.7 -5.7 AATTCGGTCAAACATCCGGT

1125 SEQ ID NO: 1428 -8.4 -23.2 64.8 -13.1 -1.7 -6.9 TGTTTGCTTGTCCGAAAATT

1141 SEQ ID NO: 1429 -8.4 -21.2 61.8 -12.8 0 -2.9 CCGGACTCTTCCGCCCAGGC

1281 SEQ ID NO: 1430 -8.4 -33.8 85.4 -22.5 -2.9 -10.5 TCGGGGCCCCAACATGGCCT

1444 SEQ ID NO: 1431 -8.4 -33.4 83.5 -21.1 -3.9 -14.4 AACAAGTTTTATCAAATTGC

1470 SEQ ID NO: 1432 -8.4 -16.3 52.4 -6.6 -1.2 -4.3 CTTCCACATCAACAAGTTTT

1480 SEQ ID NO: 1433 -8.4 -21.1 62.8 -12.7 0 -3.6 GTAACCAGCCGTCTTTGTCC

1603 SEQ ID NO: 1434 -8.4 -28 77.7 -19.6 0 -3.2 CTAAACCTTGATAGTGGAAT

2091 SEQ ID NO: 1435 -8.4 -19 57.5 -10.6 0 -3.3 TTCACACTAAACCTTGATAG

2097 SEQ ID NO: 1436 -8.4 -19 57.9 -10.6 0 -2.7 CTTTCTTCTTCACACTAAAC

2105 SEQ ID NO: 1437 -8.4 -19.5 60.5 -11.1 0 -1.9 CCTCTGAGCTTTCTTCTTCA

2113 SEQ ID NO: 1438 -8.4 -25.6 76.3 -17.2 0 -5.7 TTCCTTCCCTACACTTGCTG

2195 SEQ ID NO: 1439 -8.4 -27.3 76.4 -18.9 0 -3.6 AATAACTTAGCACATTTATA

2365 SEQ ID NO: 1440 -8.4 -16.2 52.4 -7.8 0 -4.1 CACTGTACTCTTTAGAGCAG

2509 SEQ ID NO: 1441 -8.4 -22.1 67.6 -12.1 -1.6 -7.7 GGGAAAAAGGCAAGTTAATC

3066 SEQ ID NO: 1442 -8.4 -17.9 54.9 -9.5 0 -4 TTATTTTTTGGGGAAAAAGG

3076 SEQ ID NO: 1443 -8.4 -16.9 53.3 -6.7 -1.8 -5 TGTTAATTTCCCAAATTAAC

3291 SEQ ID NO: 1444 -8.4 -17.5 54.1 -4.9 -4.2 -10.7 TTGTTTTGGTTTATAAAACA

3567 SEQ ID NO: 1445 -8.4 -16.4 53 -5.2 -2.8 -8.2 TTCCACTGACTGCATGGAGA

183 SEQ ID NO: 1446 -8.3 -24.9 71.3 -14.6 -2 -8.4 TACCCGCCACTTCCACTGAC

193 SEQ ID NO: 1447 -8.3 -29.4 77.1 -21.1 0 -2.5 CCTTCGTATAATGTTGTGAC

278 SEQ ID NO: 1448 -8.3 -21.4 63.6 -13.1 0 -3 CTGTATTCTCTGTTGCTTTC

916 SEQ ID NO: 1449 -8.3 -23.1 71.8 -14.8 0 -3.6 AGCAGTCTTGGAACCACGGG

1103 SEQ ID NO: 1450 -8.3 -26.5 73.4 -18.2 0 -5.5 TACTTTGTGGAAGATCAGCC

1254 SEQ ID NO: 1451 -8.3 -22.8 67.5 -13.6 -0.7 -5.8 GTCTGTCCGTATCCTTCATA

1376 SEQ ID NO: 1452 -8.3 -26 75.7 -17.7 0 -2.6 AAATGCCTGCAGGCTTTCTC

1782 SEQ ID NO: 1453 -8.3 -25.6 72.9 -12.8 -2.1 -17.2

133 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTTTTTGACATCCTTATTTC 1890 SEQ ID NO: 1454 -8.3 -19.7 61.4 -11.4 0 -2.2

AAATAATTCAGGGTGCAATG 1983 SEQ ID NO: 1455 -8.3 -18.2 55.8 -9.9 0 -5.4

AGAAGGCCATTGTCGATAGA 2003 SEQ ID NO: 1456 -8.3 -23 66.5 -13.6 -0.9 -9.5

AACCTTGATAGTGGAATAGA 2088 SEQ ID NO: 1457 -8.3 -19.4 59 -11.1 0 -3.3

GCTTTCTTCTTCACACTAAA 2106 SEQ ID NO: 1458 -8.3 -21.1 64.1 -12.8 0 -2.8

TTCCTCTGAGCTTTCTTCTT 2115 SEQ ID NO: 1459 -8.3 -25 75.5 -16.7 0 -5.7

CATCAGCAGGAGAAGAGATT 2150 SEQ ID NO: 1460 -8.3 -21.3 64.1 -13 0 -3.4

GAGAAGAACCCCGAATGGAC 2232 SEQ ID NO: 1461 -8.3 -23.3 63.6 -14.4 -0.3 -3.3

ATGAGTTTCGTAACCCTTAC 2662 SEQ ID NO: 1462 -8.3 -22.5 65.6 -13.5 -0.5 -4

CTGCCCTCCCGCTTACTGGA 2725 SEQ ID NO: 1463 -8.3 -32.2 83.3 -23.9 0 -3.4

CCCCTGAAAAAGGATGGAGT 2863 SEQ ID NO: 1464 -8.3 -23.5 64.7 -14 -1.1 -4.3

GTATATACTCCCTTAATAGC 3121 SEQ ID NO: 1465 -8.3 -21.3 64 -13 0 -7

TTTTGTTTTGGTTTATAAAA 3569 SEQ ID NO: 1466 -8.3 -15.7 51.8 -7.4 0.4 -6.3

ATAGGGTTGGTCTGGTTTCC 348 SEQ ID NO: 1467 -8.2 -26.1 78 -17.9 0 -2.6

CTTTGTGGAAGATCAGCCGG 1252 SEQ ID NO: 1468 -8.2 -24.9 70.1 -16.2 -0.2 -6.7

ATCGGGGCCCCAACATGGCC 1445 SEQ ID NO: 1469 -8.2 -32.5 81.7 -21.1 -2.3 -14.4

AACCAGCCGTCTTTGTCCAA 1601 SEQ ID NO: 1470 -8.2 -27.1 73.6 -18.9 0 -2.9

CAAACACCTGAGCAACAGGC 1756 SEQ ID NO: 1471 -8.2 -23.6 65.9 -12.2 -3.2 -10.5

CAGGCTTTCTCCGTGGACAA 1773 SEQ ID NO: 1472 -8.2 -26.5 73.9 -17.8 -0.2 -5.6

CTGGTACCACAATTGCAATG 1804 SEQ ID NO: 1473 -8.2 -22 63.2 -12.9 0 -9.6

AATCCTTCCCAAGTCTCACC 1927 SEQ ID NO: 1474 -8.2 -26.9 74.6 -18.7 0 -2.3

AGTCAAACACGAACGCTTCC 2211 SEQ ID NO: 1475 -8.2 -22.9 63.9 -14.7 0 -4.6

AGGAAGTCTCAAATAACTTA 2376 SEQ ID NO: 1476 -8.2 -17.2 54.7 -8.1 -0.8 -4.2

CAAAGTCCTAACCCCTTGAT 2442 SEQ ID NO: 1477 -8.2 -24.6 67.4 -16.4 0 -2.7

AAAGGGAACACTTCCCTCTA

2532 SEQ ID NO: 1478 -8.2 -23.3 66.2 -10.6 -4.5 -11.1 TAAAGGGAACACTTCCCTCT

2533 SEQ ID NO: 1479 -8.2 -23.3 66.2 -10.6 -4.5 -11.1 CCAGAGGCTCCTTATCTGCA

2761 SEQ ID NO: 1480 -8.2 -28.1 79.1 -18.7 -1.1 -5.5

AAAGAGAATCCACGCGTTCT 2797 SEQ ID NO: 1481 -8.2 -22.4 63.2 -13 -0.5 -10.2

TTCAGTGAAGATAAAGTAGA 2981 SEQ ID NO: 1482 -8.2 -16.7 54.1 -8.5 0 -7.3

GATATGAAAACCACATTAAA 3031 SEQ ID NO: 1483 -8.2 -15 48.6 -6.8 0 -3

TTCCAGATTTCTACATCCTA 3230 SEQ ID NO: 1484 -8.2 -22.9 68 -14.7 0 -3.1

134 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CAAAACAGCTGCTTTAAATG 3369 SEQ ID NO:1485 -8.2 -17.4 53.6 -8.5 0 -9.1

TAAAACATAGAAATAGCCAA 3554 SEQ ID NO: 1486 -8.2 -14.9 48.4 -6.7 0 -3.2

TTTGGTTTATAAAACATAGA 3563 SEQ ID NO:1487 -8.2 -15.3 50.5 -5.2 -1.9 -4.4

AAATGCAGAAATATTTATTT 3614 SEQ ID NO:1488 -8.2 -14.1 47.6 -5.4 -0.1 -6.7

GCATTCGAAAATACCGGAAC 31 SEQ ID NO: 1489 -8.1 -20.3 57.7 -11.7 0 -7.9

CGTCGCTGTCAAGTAGTGCG 232 SEQ ID NO: 1490 -8.1 -26.2 73.1 -16.6 -1.4 -5.5

TAAACAAGGGCCATTATTTG 321 SEQ ID NO:1491 -8.1 -19.4 57.9 -10.8 0 -7.8

TATGCACTCCGACAATTCTG 393 SEQ ID NO: 1492 -8.1 -22.7 65 -14.6 0 -5.5

GCCTATGCACTCCGACAATT 396 SEQ ID NO:1493 -8.1 -26.1 71 -17.2 -0.6 -5

GAGTTTGGCCTTCTCTGGCT 618 SEQ ID NO: 1494 -8.1 -28.5 82.7 -18.1 -2.3 -7.7

TCGCCTTCATGCTGGTGACT 745 SEQ ID NO: 1495 -8.1 -27.9 77.8 -18.6 -1.1 -8.7

CCTCCATCGCCTTCATGCTG 751 SEQ ID NO: 1496 -8.1 -29.8 79.7 -21.7 0 -4.4

GTTTCGGTGAGTGACCATTG 870 SEQ ID NO: 1497 -8.1 -24.4 70.8 -15 -1.2 -3.8

TGAACAATCGCTCACTATGT 888 SEQ ID NO: 1498 -8.1 -21.1 62 -12.3 -0.4 -3.5

ATTACACACTCTACAACTCT 995 SEQ ID NO: 1499 -8.1 -20.3 61.9 -12.2 0 -1.1

CTTGGAACCACGGGGAAGAC 1097 SEQ ID NO:1500 -8.1 -24.3 66.8 -15.4 -0.6 -6.5

CTGTCCGTATCCTTCATAAA 1374 SEQ ID NO:1501 -8.1 -23 66.1 -14.9 0 -2.1

TGTCTGTCCGTATCCTTCAT 1377 SEQ ID NO: 1502 -8.1 -26.3 76.1 -18.2 0 -2.6

TCCTCTGAGCTTTCTTCTTC 2114 SEQ ID NO:1503 -8.1 -25.3 77 -17.2 0 -5.7

TTCCTATGAGAAGAACCCCG 2239 SEQ ID NO:1504 -8.1 -24.5 66.5 -16.4 0 -2.7

TAGTGCACTGTACTCTTTAG 2514 SEQ ID NO:1505 -8.1 -21.7 67.3 -12.3 -0.2 -10.6

AACATGAGTTTCGTAACCCT 2665 SEQ ID NO: 1506 -8.1 -22.7 64.8 -13.9 -0.5 -6.1

GAAAGAGAATCCACGCGTTC 2798 SEQ ID NO:1507 -8.1 -22.1 62.6 -13 -0.1 -10

AAATGCTTGTCTTCACTATA 2908 SEQ ID NO:1508 -8.1 -19.6 60.5 -11.5 0 -3.6

ACTCTTTCTTGAAATGCTTG 2919 SEQ ID NO: 1509 -8.1 -20 61.2 -11.2 -0.5 -5.2

GAGAAGTGAATCCCAGGAAA 3256 SEQ ID NO:1510 -8.1 -21.1 61.1 -13 0 -4.9

AGCAAACATTCAAAACCCCA 3527 SEQ ID NO:1511 -8.1 -22 60.9 -13.9 0 -4.1

ATAGAAATAGCCAACACTTA 3548 SEQ ID NO: 1512 -8.1 -18.2 55.7 -10.1 0 -3.2

ATATTTATTTTGGTTTCCTT 3604 SEQ ID NO: 1513 -8.1 -19.9 62 -11.8 0 -3.2

CATAGAAATACACCAAGGGC 253 SEQ ID NO: 1514 -8 -20.6 60 -12.6 0 -3.8

TCCCCTCTGGAAACCTTCGT 291 SEQ ID NO: 1515 -8 -28.6 75.9 -19.7 -0.8 -4.2

135 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo άnding ation Duplex ture oligo oligo

TGGTCTGGTTTCCGAGAGCC 341 SEQ ID NO: 1516 -8 -28.5 80.2 -19.7 -0.6 -4.9

GAGCCTATGCACTCCGACAA

398 SEQ ID NO: 1517 -8 -26.6 72.2 -17.1 -1.4 -5.5 TGAGCCTATGCACTCCGACA

399 SEQ ID NO: 1518 -8 -27.3 74.3 -17.8 -1.4 -5.8 CCTGGTATTAACTTATTTTC

653 SEQ ID NO: 1519 -8 -19.7 60.8 -11.2 -0.2 -3.4

GAACAATCGCTCACTATGTT 887 SEQ ID NO: 1520 -8 -21.2 62.5 -12.3 -0.7 -4.2

CAACTCTCTCAAACATATGG 982 SEQ ID NO: 1521 -8 -19.2 58.4 -11.2 0 -6.7

GACTGTACTTTGTGGAAGAT 1259 SEQ ID NO: 1522 -8 -20.8 63.4 -11.9 -0.7 -5.5

CCAGGGCTGCTCTGAGGAAC 1345 SEQ ID NO: 1523 -8 -27.7 77.4 -18.1 -1 -11.2

TGTTTTCGCTGGGTCCTTCA 1572 SEQ ID NO: 1524 -8 -27.5 78.8 -19.5 0 -3.6

CTTCTGCTGTTTTCGCTGGG 1579 SEQ ID NO: 1525 -8 -26.8 77 -17.9 -0.7 -3.5

CGACCCTTCAAATCCTCTCT 1854 SEQ ID NO: 1526 -8 -26.2 71.5 -18.2 0 -2.2

CCATATCTTCGAGGATAGCT 1909 SEQ ID NO: 1527 -8 -23.8 68.8 -14.6 -0.9 -9.9

ACACTTGCTGTATTCAAAAT 2185 SEQ ID NO: 1528 -8 -18.8 57.6 -10.8 0 -3.6

CATTCCTATGAGAAGAACCC 2241 SEQ ID NO: 1529 -8 -22.4 63.9 -14.4 0 -3.1

AGCATTCCTATGAGAAGAAC 2243 SEQ ID NO: 1530 -8 -20.2 60.9 -11.5 -0.4 -4.1

CATAAACATGGTCTGCAACA 2297 SEQ ID NO:1531 -8 -20.3 60 -11.7 -0.3 -6

TAGCACATTTATAGTATCCC 2358 SEQ ID NO: 1532 -8 -22 65.9 -14 0 -4.1

GTTGTTCTTATTTTTAAAGG 2547 SEQ ID NO: 1533 -8 -17.6 56.8 -9.6 0 -4.6

TCTCTGGTCCGCTTGTGAGA 2583 SEQ ID NO: 1534 -8 -27.4 78.8 -18.7 -0.4 -4.8

TCTGCCATGAAAGAGAATCC 2806 SEQ ID NO: 1535 -8 -21.9 63.3 -13.4 -0.1 -5.1

TCAATAAGTACTCAAGTATA 3136 SEQ ID NO:1536 -8 -16.4 53.5 -8.4 0 -6.2

CCATTTCAATAAGTACTCAA 3141 SEQ ID NO: 1537 -8 -18.7 57.3 -10.7 0 -6.2

CACAGACCCCAAAACAGCTG 3378 SEQ ID NO: 1538 -8 -24.6 66.5 -16 0 -8.6

CTTCATTGTTTTTGGAAATT 3587 SEQ ID NO: 1539 -8 -18.3 57.3 -10.3 0 -3.5

AATGCAGAAATATTTATTTT 3613 SEQ ID NO: 1540 -8 -14.9 49.5 -6.3 -0.3 -7.2

AGCTCTGGCATTCGAAAATA 38 SEQ ID NO: 1541 -7.9 -21.2 61.9 -11.7 -1.6 -9.5

TCAAGTAGTGCGGATCTTCG 224 SEQ ID NO: 1542 -7.9 -23.5 68.3 -15.6 0 -5

TTAAGGCCTGGTATTAACTT

659 SEQ ID NO: 1543 -7.9 -21.4 63.5 -12.5 -0.2 -9.8 TTTAAGGCCTGGTATTAACT

660 SEQ ID NO: 1544 -7.9 -21.4 63.5 -12.5 -0.2 -9.8 TCGTTCCACCAGTTCACTGC

705 SEQ ID NO: 1545 -7.9 -27.8 78.3 -19.4 -0.1 -6.4

TTCCACCCCACACCTCTGGC 726 SEQ ID NO : 1546 -7.9 -32.4 84.5 -24.5 0 -3.4

136 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo nding ation Duplex ture oligo oligo

CTCTTCCCAGGTCCTCCATC 763 SEQ ID NO: 1547 -7.9 -30.6 85.6 -21.4 -1.2 -4.5

CCATGACACAGCATTACACA 1007 SEQ ID NO: 1548 -7.9 -23.2 66.2 -15.3 0 -4.5

AGCCTGATATCTCCTTGGAA 1043 SEQ ID NO: 1549 -7.9 -24.8 70.9 -16.9 0 -5.7

GTGTTTGCTTGTCCGAAAAT 1142 SEQ ID NO: 1550 -7.9 -22.3 64.4 -14.4 0 -3.6

GCCATCGCTTCAGCGTGGTG 1159 SEQ ID NO: 1551 -7.9 -29.8 81 -18.1 -3.8 -13.6

TCCAAGAGCCATCGCTTCAG 1166 SEQ ID NO: 1552 -7.9 -26.6 73.8 -17.2 -1.4 -4.2

CTGCGAAGCTCTGCTTCTTT 1202 SEQ ID NO: 1553 -7.9 -25.7 73.6 -14.1 -3.7 -10.4

ACCATCAGCCGGACTCTTCC 1289 SEQ ID NO: 1554 -7.9 -29.3 79.4 -20.7 -0.5 -6.7

GTCCGTATCCTTCATAAAAC 1372 SEQ ID NO: 1555 -7.9 -21.6 62.8 -13.7 0 -2.6

TCTCCAGGCATGGTTAGGCA 1415 SEQ ID NO: 1556 -7.9 -28 80.2 -18.6 -1.4 -9.4

TATTTCTGCACAGTTCCTCA 1876 SEQ ID NO: 1557 -7.9 -24.3 72.4 -16.4 0 -4.8

ATAGAAAATAATTCAGGGTG 1988 SEQ ID NO: 1558 -7.9 -16 51.7 -6.6 -1.4 -3.9

TGAGGTGACTGTAAGGCGGT 2277 SEQ ID NO: 1559 -7.9 -25.1 72.1 -16.3 -0.7 -5.2

TTATCTGCATGGTTCTGAGT 2750 SEQ ID NO: 1560 -7.9 -23.2 70.7 -15.3 0 -5

ATGAAAGAGAATCCACGCGT 2800 SEQ ID NO: 1561 -7.9 -21.6 61 -13 -0.1 -8.9

AAATGCTTGCCTGAGAGTTT 3094 SEQ ID NO: 1562 -7.9 -22.7 66.3 -14.8 0 -3.9

CCCAAAACAGCTGCTTTAAA 3371 SEQ ID NO: 1563 -7.9 -21.4 60.5 -12.8 0 -9.1

CTCACAGACCCCAAAACAGC 3380 SEQ ID NO: 1564 -7.9 -25 68 -17.1 0 -2.8

CATAGAAATAGCCAACACTT 3549 SEQ ID NO: 1565 -7.9 -19.2 57.4 -11.3 0 -3.2

TTTGTTTTGGTTTATAAAAC 3568 SEQ ID NO: 1566 -7.9 -15.8 52 -6.2 -1.7 -7.1

TTGGTTTCCTTCATTGTTTT 3595 SEQ ID NO: 1567 -7.9 -22.8 69.4 -14.9 0 -3.2

TACTGTCGGAAGTCAACCAG 56 SEQ ID NO: 1568 -7.8 -22.8 65.9 -14.5 -0.2 -4.5

TCATAGAAATACACCAAGGG 254 SEQ ID NO: 1569 -7.8 -19.2 57.5 -11.4 0 -3.8

AACTGATCTGGGGCAGTCTT 440 SEQ ID NO: 1570 -7.8 -25 73.2 -15.6 -1.5 -5.4

AAGGCCTGGTATTAACTTAT 657 SEQ ID NO: 1571 -7.8 -21.3 63.2 -12.5 -0.2 -9.8

AACAATCGCTCACTATGTTT 886 SEQ ID NO: 1572 -7.8 -20.7 61.5 -12.3 -0.3 -3.8

CTGAACAATCGCTCACTATG 889 SEQ ID NO: 1573 -7.8 -20.8 61 -12.3 -0.4 -3.3

TGCTTGTCCGAAAATTCGGT 1137 SEQ ID NO: 1574 -7.8 -23.4 65.3 -12.8 -2.8 -11.7

ACTGTACTTTGTGGAAGATC 1258 SEQ ID NO: 1575 -7.8 -20.6 63.6 -11.9 -0.7 -4.8

CAGCCGGACTCTTCCGCCCA 1284 SEQ ID NO: 1576 -7.8 -33.3 83.9 -22.6 -2.9 -9.2

ATCAAATTGCACGGCATCGG 1460 SEQ ID NO: 1577 -7.8 -23.4 64.8 -14.6 -0.9 -7.3

137 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CAAGGTGCCATTTGGTAACC

1644 SEQ ID NO: 1578 -7.8 -24.7 69.4 -16.3 -0.3 -7.5 TGGACAAACACCTGAGCAAC

1760 SEQ ID NO: 1579 -7.8 -21.9 62.4 -13.6 -0.1 -4.2 TGCAACATGAGGTGACTGTA

2284 SEQ ID NO: 1580 -7.8 -22.3 66 -13.6 -0.7 -5.7 TTAAAACCCACTTTTTAAAC

2398 SEQ ID NO: 1581 -7.8 -16.6 51.8 -7.8 -0.9 -4.6 TCTAGTGCACTGTACTCTTT

2516 SEQ ID NO: 1582 -7.8 -23.3 71.6 -14.2 -0.2 -10.6 TTTAAAGGGAACACTTCCCT

2535 SEQ ID NO: 1583 -7.8 -22.2 63.7 -10.6 -3.8 -12 AGAATCCACGCGTTCTGATG

2793 SEQ ID NO: 1584 -7.8 -23.8 66.8 -15.2 -0.2 -9.1 AACCGAGTCCAAGAGCATTC

2824 SEQ ID NO: 1585 -7.8 -24.1 68 -16.3 0 -4.1 CAGGTAACTCTTTCTTGAAA

2925 SEQ ID NO: 1586 -7.8 -19.3 59.5 -10.3 -1.1 -6.1 TCTTTTGATATGAAAACCAC

3037 SEQ ID NO: 1587 -7.8 -17.5 54.4 -9.7 0 -3 TTACAATGACAATTCTTTAG

3437 SEQ ID NO: 1588 -7.8 -16.1 52.4 -8.3 0 -3.1 ATTACAATGACAATTCTTTA

3438 SEQ ID NO: 1589 -7.8 -16.1 52.2 -8.3 0 -3.1 TATTACAATGACAATTCTTT

3439 SEQ ID NO: 1590 -7.8 -16.1 52.2 -8.3 0 -2.7 TTATTACAATGACAATTCTT

3440 SEQ ID NO: 1591 -7.8 -16.1 52.2 -8.3 0 -3.1 TTGTTTTTGGAAATTTTGTT

3582 SEQ ID NO: 1592 -7.8 -17.7 56.4 -9.9 0 -5.3 CATGGGCTTGCATTGTCCTG

7 SEQ ID NO: 1593 -7.7 -27 76.3 -18.6 -0.5 -8 GGTCTATTTTGAGCAAAGAT

467 SEQ ID NO: 1594 -7.7 -20 61.3 -12.3 0.5 -5.9 AGAGTTCAGCTTTGTTGACT

580 SEQ ID NO: 1595 -7.7 -22.9 70.5 -15.2 0 -4.5 ACAAAAACCAGAGAGAGTTC

593 SEQ ID NO: 1596 -7.7 -18.5 56.7 -10.8 0 -3.1 CCAGTTCACTGCCGTAGGCA

697 SEQ ID NO: 1597 -7.7 -29.4 80.4 -17.3 -4.4 -11 ATGGGCGAGAGGCAAGAAAG

966 SEQ ID NO: 1598 -7.7 -22.4 63.7 -13.1 -1.5 -4 GGCCCCAACATGGCCTGCGG

1440 SEQ ID NO: 1599 -7.7 -33.6 83.3 -22.8 -3.1 -11 GCTTCTGCTGTTTTCGCTGG

1580 SEQ ID NO: 1600 -7.7 -27.4 78.8 -18.6 -1 -4.8 GAGAAATGCCTGCAGGCTTT

1785 SEQ ID NO: 1601 -7.7 -25.1 70.7 -12.8 -2.1 -17.3 TGAGAAATGCCTGCAGGCTT

1786 SEQ ID NO: 1602 -7.7 -25 70.2 -12.8 -2.1 -17.2 CCCCGAATGGACAAGTCAAA

2224 SEQ ID NO: 1603 -7.7 -23.6 63.7 -15.3 -0.3 -6.1 GACAGAAGATTTAAAACCCA

2408 SEQ ID NO: 1604 -7.7 -18.7 55.8 -11 0 -5 TCTGCCCTCCCGCTTACTGG

2726 SEQ ID NO: 1605 -7.7 -32 83.8 -24.3 0 -3.2 TGAAAGAGAATCCACGCGTT

2799 SEQ ID NO: 1606 -7.7 -21.7 61.3 -13 0.7 -10 TAACCCCTGAAAAAGGATGG

2866 SEQ ID NO: 1607 -7.7 -20.9 58.9 -12.4 -0.6 -4.3 GTTGGCCTTTACACAGAGTG

3006 SEQ ID NO: 1608 -7.7 -24.7 72.4 -16.3 -0.4 -8

138 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GGAAAAAGGCAAGTTAATCC 3065 SEQ ID NO: 1609 -7.7 -18.7 56.2 -11 0 -4

CCCTTAATAGCTTTAAAGAA 3112 SEQ ID NO: 1610 -7.7 -18.8 56.6 -10.6 0 -8.1

GAATTTTGGCTTGTCAAACA 3210 SEQ ID NO:1611 -7.7 -20 60.2 -9.4 -2.9 -7.9

CTTTCCAGATTTCTACATCC 3232 SEQ ID NO: 1612 -7.7 -23.3 69 -15.6 0 -3.1

CCCTGGAGAAGTGAATCCCA 3261 SEQ ID NO: 1613 -7.7 -26.8 72.3 -18.3 -0.6 -4.4

AAATCCCTGGAGAAGTGAAT 3265 SEQ ID NO: 1614 -7.7 -20.7 60.3 -13 0 -4.8

CTCTGGCATTCGAAAATACC 36 SEQ ID NO: 1615 -7.6 -21.6 61.9 -14 0 -7.2

TTGGGTCTCGTGGCGTACCA 140 SEQ ID NO: 1616 -7.6 -29 79.7 -19.3 -2.1 -7.4

CCCGCCACTTCCACTGACTG 191 SEQ ID NO: 1617 -7.6 -30.4 78.6 -22.8 0 -2.6

GTCTGGTTTCCGAGAGCCTA 339 SEQ ID NO: 1618 -7.6 -27.9 79.1 -19.7 -0.3 -4.7

ATGTACGTGATGGCTTCATT 560 SEQ ID NO: 1619 -7.6 -22.9 67.4 -14.2 -0.7 -9.8

TTTTAAGGCCTGGTATTAAC 661 SEQ ID NO: 1620 -7.6 -20.6 62 -12.5 0 -8.2

ATCGCCTTCATGCTGGTGAC 746 SEQ ID NO: 1621 -7.6 -27 75.8 -17.8 -1.6 -9.6

GATTGACTGTATTCTCTGTT 922 SEQ ID NO: 1622 -7.6 -21.3 66.3 -13.7 0 -2.7

CTGGGCAAGGATTGACTGTA 931 SEQ ID NO: 1623 -7.6 -23.6 68.6 -14.9 -1 -4.6

TATGGGCGAGAGGCAAGAAA 967 SEQ ID NO: 1624 -7.6 -22.1 62.9 -13.6 -0.7 -4

TTTGCTTGTCCGAAAATTCG 1139 SEQ ID NO: 1625 -7.6 -21.2 60.8 -12.8 -0.6 -7.3

ACTTTGTGGAAGATCAGCCG 1253 SEQ ID NO: 1626 -7.6 -23.9 68.2 -15.4 -0.7 -6.7

AAATACATTTGGCCCTTTCA 1542 SEQ ID NO: 1627 -7.6 -22.6 64.7 -15 0 -6.6

ACCAGCCGTCTTTGTCCAAA 1600 SEQ ID NO: 1628 -7.6 -27.1 73.6 -19.5 0 -4.7

ATGAGAAATGCCTGCAGGCT 1787 SEQ ID NO: 1629 -7.6 -24.9 69.8 -12.8 -2.1 -17.2

GAACATAATGTCTCAACATC 1823 SEQ ID NO: 1630 -7.6 -18 56.3 -8.8 -1.6 -6.8

TCTCACCATATCTTCGAGGA 1914 SEQ ID NO: 1631 -7.6 -24 69.8 -16.4 0 -6.6

GTCGATAGAAAATAATTCAG 1992 SEQ ID NO: 1632 -7.6 -15.4 50.2 -6.3 -1.4 -7.3

CTTCCTTCCCTACACTTGCT 2196 SEQ ID NO: 1633 -7.6 -28.2 78.6 -20.6 0 -3.6

AACACGAACGCTTCCTTCCC

2206 SEQ ID NO:1634 -7.6 -26.7 70.4 -19.1 0 -4.6 AAACACGAACGCTTCCTTCC

2207 SEQ ID NO: 1635 -7.6 -24 65.2 -16.4 0 -4.2 ACCCCGAATGGACAAGTCAA

2225 SEQ ID NO: 1636 -7.6 -24.5 66.1 -16.3 -0.3 -6.1

TAAAACCCACTTTTTAAACT

2397 SEQ ID NO: 1637 -7.6 -17.4 53.2 -9.3 -0.2 -4.4

CTCCCTTAATAGCTTTAAAG

3114 SEQ ID NO: 1638 -7.6 -20.2 60.2 -12.1 0 -7.6

AGAACATTTGCTTATTACTG

3162 SEQ ID NO: 1639 -7.6 -18.4 57.5 -10.8 0 -3.6

139 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

TTATTGACTTTTTGTGCAAT 3497 SEQ ID NO:1640 -7.6 -19 59.1 -10.4 -0.9 -5.6

CACTGACTGCATGGAGAGGT 180 SEQ ID NO: 1641 -7.5 -24.8 71.9 -17.3 0 -5

TCGAATAAGCAAAGCATCCT 508 SEQ ID NO: 1642 -7.5 -21 60.4 -12.6 -0.7 -4.9

ACACCCTCTAATAAGAGTTT 632 SEQ ID NO: 1643 -7.5 -21.3 63.1 -12.3 -1.4 -4.7

TAAGGCCTGGTATTAACTTA 658 SEQ ID NO: 1644 -7.5 -21 62.6 -12.5 -0.2 -9.8

CAGCCTGATATCTCCTTGGA 1044 SEQ ID NO: 1645 -7.5 -26.2 74.5 -18.7 0 -6.4

CAAACATCCGGTTCAGCAGT 1117 SEQ ID NO: 1646 -7.5 -24.7 69.5 -16.5 -0.5 -6.6

CTTGGAGGCAAAGTCCAAGA 1179 SEQ ID NO: 1647 -7.5 -23.3 66.8 -12.3 -3.5 -9.6

ATCAGCCGGACTCTTCCGCC 1286 SEQ ID NO: 1648 -7.5 -31 81.5 -20.6 -2.9 -9.2

CAACAAGTTTTATCAAATTG 1471 SEQ ID NO: 1649 -7.5 -15.2 49.9 -6.6 -1 -4

TTTCTTCCACATCAACAAGT 1483 SEQ ID NO: 1650 -7.5 -21.4 63.9 -13.9 0 -2.8

ATTTCTGCACAGTTCCTCAA 1875 SEQ ID NO: 1651 -7.5 -23.9 70.5 -16.4 0 -4.9

ACCATATCTTCGAGGATAGC 1910 SEQ ID NO: 1652 -7.5 -23.1 67.5 -14.4 -0.9 -9.9

GTTCCGCAGCTCTGGCCTTT 2043 SEQ ID NO: 1653 -7.5 -31.1 85.4 -22.6 -0.9 -7.2

GGTCATCTATCTGCGACCTG 2068 SEQ ID NO: 1654 -7.5 -26.1 74.4 -16.9 -1.7 -6

CCTATGAGAAGAACCCCGAA 2237 SEQ ID NO: 1655 -7.5 -23.9 64.2 -16.4 0 -2.8

AGCACATTTATAGTATCCCC 2357 SEQ ID NO:1656 -7.5 -24.3 70.2 -16.8 0 -4.1

TTTTAAAGGGAACACTTCCC 2536 SEQ ID NO: 1657 -7.5 -21.4 62.2 -10.6 -3.3 -11.4

ACGCGTTCTGATGAGCACCC 2786 SEQ ID NO: 1658 -7.5 -28.1 75.4 -19.6 -0.4 -9.7

CCAGGTAACTCTTTCTTGAA 2926 SEQ ID NO: 1659 -7.5 -22 65.4 -13.6 -0.8 -4.5

ACATCCTAGAATTTTGGCTT 3218 SEQ ID NO:1660 -7.5 -22.1 65.4 -14.6 0 -3.7

AGAAGTGAATCCCAGGAAAT 3255 SEQ ID NO:1661 -7.5 -20.5 59.9 -13 0 -4.9

GAACTGCTGTTAATTTCCCA 3298 SEQ ID NO:1662 -7.5 -23.3 66.8 -14.9 -0.7 -7.7

GCACTCCGACAATTCTGCAA 390 SEQ ID NO: 1663 -7.4 -24.8 68.6 -16.7 -0.4 -4.9

AGCCTATGCACTCCGACAAT 397 SEQ ID NO: 1664 -7.4 -26 71 -17.1 -1.4 -5.5

GGCTTCATTTCCAAGGGTAT 549 SEQ ID NO:1665 -7.4 -25 72.6 -17.6 0 -3.7

GAGAGTTCAGCTTTGTTGAC 581 SEQ ID NO: 1666 -7.4 -22.6 69.8 -15.2 0 -4.5

CAGGTCCTCCATCGCCTTCA 756 SEQ ID NO: 1667 -7.4 -30.6 83.1 -21.9 -1.2 -4.6

AGGATTGACTGTATTCTCTG 924 SEQ ID NO:1668 -7.4 -21.2 65.5 -13.8 0 -3.3

AAAGTATCATCTGGGCAAGG 941 SEQ ID NO: 1669 -7.4 -21.3 63.4 -13.9 0 -4

TGGGCGAGAGGCAAGAAAGA 965 SEQ ID NO:1670 -7.4 -23 64.9 -14 -1.5 -4

140 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCGATTTTAGCTCCATGACA 1019 SEQ ID NO:1671 -7.4 -24.7 69.1 -17.3 0 -4.8

GGAACCACGGGGAAGACAGT 1094 SEQ ID NO: 1672 -7.4 -25.2 69.1 -17 -0.6 -6.5

TGGAAGATCAGCCGGTCCCA 1247 SEQ ID NO: 1673 -7.4 -28.9 77.2 -21 -0.2 -6.7

TGCACTCTGTCTGTCCGTAT 1384 SEQ ID NO: 1674 -7.4 -26.7 77.3 -19.3 0 -4.7

GGCATCGGGGCCCCAACATG 1448 SEQ ID NO: 1675 -7.4 -31.2 79.5 -20.7 -1.1 -14.4

TCATTTCTTCCACATCAACA 1486 SEQ ID NO:1676 -7.4 -22 65.3 -14.6 0 -1

GTAGCCCTGAAATACATTTG 1551 SEQ ID NO:1677 -7.4 -21.6 62.9 -14.2 0 -3.9

CACCTGAGCAACAGGCTCAC 1752 SEQ ID NO:1678 -7.4 -26.3 73.6 -14.8 -4.1 -10.5

GGGCCCAGGAACATAATGTC 1831 SEQ ID NO:1679 -7.4 -25.5 70.9 -16.7 -0.2 -10.8

CAAATCCTCTCTTTTGGGCC 1846 SEQ ID NO: 1680 -7.4 -25.7 72.4 -17.8 -0.1 -7.8

AGTTCCGCAGCTCTGGCCTT 2044 SEQ ID NO: 1681 -7.4 -31 85.4 -22.6 -0.9 -7.2

TTCCCTACACTTGCTGTATT 2191 SEQ ID NO:1682 -7.4 -24.9 72 -16.8 -0.4 -4

CAAACACGAACGCTTCCTTC 2208 SEQ ID NO: 1683 -7.4 -22.7 63 -15.3 0 -4.6

ATGGACAAGTCAAACACGAA

2218 SEQ ID NO: 1684 -7.4 -18.7 55.8 -11.3 0 -6.1 AATGGACAAGTCAAACACGA

2219 SEQ ID NO: 1685 -7.4 -18.7 55.8 -11.3 0 -6.1 AACATGGTCTGCAACATGAG

2293 SEQ ID NO: 1686 -7.4 -21.2 62.7 -11.8 -2 -9.1

AAACTGAGGAAGTCTCAAAT 2382 SEQ ID NO:1687 -7.4 -17.6 54.9 -8.4 -1.8 -5

TTAAAGGGAACACTTCCCTC 2534 SEQ ID NO:1688 -7.4 -22.5 64.7 -10.6 -4.5 -11.9

TATATACTCCCTTAATAGCT 3120 SEQ ID NO: 1689 -7.4 -21 62.8 -13.6 0 -4.4

ACTTTCCAGATTTCTACATC 3233 SEQ ID NO: 1690 -7.4 -21.5 65.7 -14.1 0 -3.1

GTTGTGCTTGTATATAATAC 3407 SEQ ID NO: 1691 -7.4 -18.8 59.5 -10.9 -0.2 -3.8

GGAAATTTTGTTTTGGTTTA 3574 SEQ ID NO:1692 -7.4 -18.5 58.1 -11.1 0 -5.3

AGCCTAAACAAGGGCCATTA 325 SEQ ID NO:1693 -7.3 -23.9 66.6 -14.7 -1.9 -8

TATGTACGTGATGGCTTCAT 561 SEQ ID NO: 1694 -7.3 -22.5 66.5 -14.2 -0.5 -9.8

GAGAGAGTTCAGCTTTGTTG 583 SEQ ID NO: 1695 -7.3 -22.4 69.4 -14.5 -0.3 -4.7

GAGGCTTGGGCTTCCGTCTG 787 SEQ ID NO: 1696 -7.3 -29.5 82.4 -20.8 -1.3 -7.2

CTCTACAACTCTCTCAAACA 987 SEQ ID NO:1697 -7.3 -20.4 61.6 -13.1 0 -0.2

CTTGTCCGAAAATTCGGTCA 1135 SEQ ID NO: 1698 -7.3 -22.7 64.1 -13.2 -2.2 -11.1

GTCTCCAGGCATGGTTAGGC 1416 SEQ ID NO: 1699 -7.3 -28.5 83 -19.7 -1.4 -9.4

CAACATCTGGTACCACAATT 1810 SEQ ID NO:1700 -7.3 -21.5 62.6 -13.3 0 -9.6

TCTCAACATCTGGTACCACA 1813 SEQ ID NO: 1701 -7.3 -23.8 69.2 -15.6 0 -9.6

141 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GACCCTTCAAATCCTCTCTT 1853 SEQ ID NO: 1702 -7.3 -25.5 71.9 -18.2 0 -1.9

ACGACCCTTCAAATCCTCTC 1855 SEQ ID NO: 1703 -7.3 -25.5 70.3 -18.2 0 -3.5

ATTTCCTCTGAGCTTTCTTC 2117 SEQ ID NO: 1704 -7.3 -24.1 73.4 -16.8 0 -5.2

CTTCCCTACACTTGCTGTAT 2192 SEQ ID NO: 1705 -7.3 -25.7 73.6 -17.6 -0.6 -4

GTCAAACACGAACGCTTCCT 2210 SEQ ID NO: 1706 -7.3 -23.8 65.5 -16.5 0 -4.6

GGATCTGCCCTCCCGCTTAC 2729 SEQ ID NO: 1707 -7.3 -31.7 83.4 -24.4 0 -6.3

GTGAAGATAAAGTAGACAGT 2977 SEQ ID NO: 1708 -7.3 -17.6 56 -10.3 0 -2.9

TTACTGTCCATTTCAATAAG 3148 SEQ ID NO: 1709 -7.3 -18.8 58.3 -11.5 0 -3

CCTGGAGAAGTGAATCCCAG 3260 SEQ ID NO: 1710 -7.3 -24.8 69.2 -15.7 -1.8 -6.4

CAGTCAAATGTGGCAAAGAC 3330 SEQ ID NO:1711 -7.3 -19.9 59.6 -11.5 -1 -5.4

TCAATTCAGTCAAATGTGGC 3336 SEQ ID NO: 1712 -7.3 -20.7 62.7 -13.4 0 -2.8

CGAATAAGCAAAGCATCCTT 507 SEQ ID NO: 1713 -7.2 -20.7 59.5 -12.6 -0.7 -4.4

TAAGAGTTTGGCCTTCTCTG 621 SEQ ID NO: 1714 -7.2 -23.6 70.3 -15 -1.2 -9.9

ATTTTAAGGCCTGGTATTAA 662 SEQ ID NO: 1715 -7.2 -20.4 61.4 -12.5 0 -8.7

GACACAGCATTACACACTCT 1003 SEQ ID NO: 1716 -7.2 -22.9 67.4 -15.7 0 -4.1

GTACTTTGTGGAAGATCAGC 1255 SEQ ID NO: 1717 -7.2 -22 67 -13.9 -0.7 -5.4

GCAGACACCGGGGCGGCTCC 1313 SEQ ID NO: 1718 -7.2 -33.5 85.6 -24.6 -1.7 -8.7

GGGCTGCTCTGAGGAACGTC 1342 SEQ ID NO: 1719 -7.2 -27.4 77.4 -20.2 0 -6.6

TCCAGTCTCCAGGCATGGTT 1420 SEQ ID NO: 1720 -7.2 -28.9 82.8 -20.2 -1.4 -9.4

AGCTTTCTTCTTCACACTAA 2107 SEQ ID NO: 1721 -7.2 -21.8 66.6 -14.6 0 -4.3

ACTGTAAGGCGGTGTTCTGT 2270 SEQ ID NO: 1722 -7.2 -25.3 74 -17.6 -0.2 -5.2

TTTAAAACCCACTTTTTAAA 2399 SEQ ID NO: 1723 -7.2 -16.5 51.6 -7.6 -1.7 -6.2

TTTTTAAAGGGAACACTTCC 2537 SEQ ID NO: 1724 -7.2 -19.5 58.9 -10.6 -1.5 -11

AGGTAACTCTTTCTTGAAAT 2924 SEQ ID NO: 1725 -7.2 -18.6 58.2 -8.5 -2.9 -7.9

ATAAGTACTCAAGTATATAC 3133 SEQ ID NO: 1726 -7.2 -15.9 52.7 -8.7 0 -7

GTCAAACACATTTCATAGAA 3198 SEQ ID NO: 1727 -7.2 -17.6 55.3 -10.4 0 -3.5

TGGCTTGTCAAACACATTTC 3204 SEQ ID NO: 1728 -7.2 -21.3 63.7 -13.2 -0.7 -7.2

TACATCCTAGAATTTTGGCT 3219 SEQ ID NO: 1729 -7.2 -21.7 64.5 -14.5 0 -3.8

TTGTGCTTGTATATAATACA 3406 SEQ ID NO: 1730 -7.2 -18.3 57.7 -9.7 -1.3 -6

TAGAAATAGCCAACACTTAA 3547 SEQ ID NO: 1731 -7.2 -17.5 54 -10.3 0 -3.2

CCGCCACTTCCACTGACTGC 190 SEQ ID NO: 1732 -7.1 -30.2 79.4 -23.1 0 -2.8

142 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Du lex ture oligo oligo

TCCACCCCACACCTCTGGCC 725 SEQ ID NO: 1733 -7.1 -34.3 87.3 -27.2 0 -6.2

ACTGTATTCTCTGTTGCTTT 917 SEQ ID NO: 1734 -7.1 -22.9 70.6 -15.8 0 -3.6

AAACATCCGGTTCAGCAGTC 1116 SEQ ID NO: 1735 -7.1 -24.4 69.9 -16.6 -0.5 -6.6

CGGCTCCTGTCACCATCAGC 1300 SEQ ID NO: 1736 -7.1 -30.1 82.2 -22.2 -0.6 -5.6

CACGGCATCGGGGCCCCAAC 1451 SEQ ID NO:1737 -7.1 -32.2 79.9 -22 -1.6 -14.4

ACACGAACGCTTCCTTCCCT 2205 SEQ ID NO: 1738 -7.1 -28.3 74.2 -21.2 0 -4.6

GGTGACTGTAAGGCGGTGTT 2274 SEQ ID NO: 1739 -7.1 -25.8 74.3 -18 -0.4 -5.2

GCAACATGAGGTGACTGTAA 2283 SEQ ID NO: 1740 -7.1 -21.6 63.9 -13.6 -0.7 -5.5

GAAAGTGTGTATTACCATAA 2312 SEQ ID NO: 1741 -7.1 -18.2 56.5 -11.1 0 -3.5

GCTTGTCTTCACTATAGAAT

2904 SEQ ID NO: 1742 -7.1 -20.9 64.4 -13.8 0 -6 TGCTTGTCTTCACTATAGAA

2905 SEQ ID NO: 1743 -7.1 -20.9 64.3 -13.8 0 -6 CAATGACAATTCTTTAGTGC

3434 SEQ ID NO: 1744 -7.1 -19.1 58.9 -12 0 -2.7

CATTCGAAAATACCGGAACA 30 SEQ ID NO: 1745 -7 -19.2 55.4 -11.7 0 -7.9

GGCCTCGTTCCACCAGTTCA 709 SEQ ID NO: 1746 -7 -30.8 84 -23.8 0 -6.4

ACAACTCTCTCAAACATATG 983 SEQ ID NO: 1747 -7 -18.2 56.4 -11.2 0 -6.2

ATGAGCAGCCTGATATCTCC 1049 SEQ ID NO: 1748 -7 -25.8 74.1 -18.8 0 -6.4

AAATTCGGTCAAACATCCGG 1126 SEQ ID NO: 1749 -7 -21.3 60.2 -13.1 -1.1 -6.3

TTGCTTGTCCGAAAATTCGG 1138 SEQ ID NO: 1750 -7 -22.3 62.8 -12.8 -2.5 -11.1

TCACCATCAGCCGGACTCTT 1291 SEQ ID NO: 1751 -7 -28 77 -21 0 -6.7

CAGGGCTGCTCTGAGGAACG 1344 SEQ ID NO:1752 -7 -26.5 73.7 -18.2 -0.5 -10.4

ACATAATGTCTCAACATCTG 1821 SEQ ID NO:1753 -7 -19 58.8 -10.8 -1.1 -6.5

TAGTTCCGCAGCTCTGGCCT 2045 SEQ ID NO: 1754 -7 -30.6 84.4 -22.6 -0.9 -7.2

TCACACTAAACCTTGATAGT 2096 SEQ ID NO: 1755 -7 -20.1 60.5 -13.1 0 -3.2

TTAGCACATTTATAGTATCC 2359 SEQ ID NO: 1756 -7 -20.1 62.3 -13.1 0 -4.1

ACTTAGCACATTTATAGTAT 2361 SEQ ID NO:1757 -7 -18.8 59.5 -11.8 0 -3.3

CCACTTTTTAAACTGAGGAA 2391 SEQ ID NO:1758 -7 -19.3 57.9 -12.3 0 -4.4

TCTTTAGAGCAGCAGACAGC 2501 SEQ ID NO: 1759 -7 -24.1 72.4 -16.4 -0.5 -5.4

CTCTAGTGCACTGTACTCTT 2517 SEQ ID NO: 1760 -7 -24.1 73.3 -15.8 -0.2 -10.6

GTGAGAAGGGACAGTAGCAG 2616 SEQ ID NO: 1761 -7 -23 68.8 -16 0 -4.1

TCCTTATCTGCATGGTTCTG 2753 SEQ ID NO: 1762 -7 -24.7 73.1 -17.7 0 -5

GTACTCAAGTATATACTCCC 3129 SEQ ID NO: 1763 -7 -22.2 66.5 -14.4 0 -9.2

143 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo AAAATCCCTGGAGAAGTGAA

3266 SEQ ID NO: 1764 -7 -20 58.5 -13 0 -4.8 AAAAATCCCTGGAGAAGTGA

3267 SEQ ID NO: 1765 -7 -20 58.5 -13 0 -4.6 TGAACTGCTGTTAATTTCCC

3299 SEQ ID NO: 1766 -7 -22.6 65.6 -14.7 -0.7 -7.7 ATTATTGACTTTTTGTGCAA

3498 SEQ ID NO: 1767 -7 -19 59.1 -11.5 -0.2 -5.4 TTTGGTTTCCTTCATTGTTT

3596 SEQ ID NO: 1768 -7 -22.8 69.4 -15.8 0 -3.2 GCGTGTTGGTCGGAAGAGTA

82 SEQ ID NO: 1769 -6.9 -25.3 72.4 -17.6 -0.6 -4 GTAGTGCGGATCTTCGTGCA

220 SEQ ID NO: 1770 -6.9 -26.8 76.3 -18 -1.9 -7 ATAGAAATACACCAAGGGCT

252 SEQ ID NO: 1771 -6.9 -20.8 60.7 -13.9 0 -3.8 AATGTTGTGACATCATCATA

269 SEQ ID NO: 1772 -6.9 -19.2 59.6 -10.6 -1.7 -6.2 TTGGTCTGGTTTCCGAGAGC

342 SEQ ID NO: 1773 -6.9 -26.6 76.9 -19.7 4.7 -0.2 ACAATTCTGCAACCTGTTTA

382 SEQ ID NO: 1774 -6.9 -21.6 63.6 -14.7 0 -4.9 AGCATCCTTGTTCAATAATC

496 SEQ ID NO: 1775 -6.9 -21 63.4 -14.1 0 -4.1 TTGAGGTCATCCATGAGCAG

1061 SEQ ID NO: 1776 -6.9 -24.4 71.7 -16.2 -1.2 -5.3 ACACCTGAGCAACAGGCTCA

1753 SEQ ID NO: 1777 -6.9 -26.3 73.6 -15.4 -4 -10.5 AACATCTGGTACCACAATTG

1809 SEQ ID NO: 1778 -6.9 -20.8 61.3 -13 0 -9.6 GCTCTGGCCTTTTCGCCTTC

2035 SEQ ID NO: 1779 -6.9 -30.6 84.6 -22.5 -1.1 -6.5 TCAAACACGAACGCTTCCTT

2209 SEQ ID NO: 1780 -6.9 -22.7 63 -15.8 0 -4.6 ACCCACTTTTTAAACTGAGG

2393 SEQ ID NO: 1781 -6.9 -21.6 62.7 -14.7 0 -4.4 ATTTTTAAAGGGAACACTTC

2538 SEQ ID NO: 1782 -6.9 -17.5 55.2 -10.6 0 -5.3 ATCTCTGGTCCGCTTGTGAG

2584 SEQ ID NO: 1783 -6.9 -26.8 77.3 -19.2 -0.4 -4.1 AGTACTCAAGTATATACTCC

3130 SEQ ID NO: 1784 -6.9 -20.2 62.9 -12.5 0 -9.2 TGTTGTGCTTGTATATAATA

3408 SEQ ID NO: 1785 -6.9 -18.6 58.9 -11.7 0 -5.2 GTGTTATTACAATGACAATT

3443 SEQ ID NO: 1786 -6.9 -17.1 54.4 -9.5 -0.5 -6.3 TGTTTTTGGAAATTTTGTTT

3581 SEQ ID NO: 1787 -6.9 -17.7 56.4 -10.8 0 -5.3 GGCATTCGAAAATACCGGAA

32 SEQ ID NO: 1788 -6.8 -21.3 59.4 -14 0 -7.9 CCAGCTCTGGCATTCGAAAA

40 SEQ ID NO: 1789 -6.8 -24.2 67 -15.8 -1.6 -9.5 ACCAGCTCTGGCATTCGAAA

41 SEQ ID NO: 1790 -6.8 -25.1 69.6 -16.7 -1.6 -9.9 CATTTCCAAGGGTATCATAA

544 SEQ ID NO: 1791 -6.8 -20.7 61.8 -13.9 0 -3.6 TTGGCCTTCTCTGGCTTGTC

614 SEQ ID NO: 1792 -6.8 -28.3 82.7 -19.2 -2.3 -7.2 ACCAGTTCACTGCCGTAGGC

698 SEQ ID NO: 1793 -6.8 -28.9 80 -18.8 -3.3 -10 CAATCGCTCACTATGTTTCG

884 SEQ ID NO: 1794 -6.8 -22.4 64.8 -15.6 0 -2.7

144 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo άnding ation Duplex ture oligo oligo

ACTCTACAACTCTCTCAAAC 988 SEQ ID NO: 1795 -6.8 -19.9 61 -13.1 0 -0.2

TTCGGTCAAACATCCGGTTC 1123 SEQ ID NO: 1796 -6.8 -24.4 68.6 -15.9 -1.7 -6.6

TGCGAAGCTCTGCTTCTTTC 1201 SEQ ID NO: 1797 -6.8 -25.2 73.3 -14.7 -3.7 -10.4

CGTATCCTTCATAAAACTGA 1369 SEQ ID NO: 1798 -6.8 -19.5 58.1 -12.7 0 -2.5

CCAAAGCTTCTGCTGTTTTC 1585 SEQ ID NO:1799 -6.8 -24 70.2 -15.5 -1.7 -7

TTTCTGCACAGTTCCTCAAA 1874 SEQ ID NO: 1800 -6.8 -23.2 68.2 -16.4 0 -4.9

GGCCTTTTCGCCTTCATTGT 2030 SEQ ID NO:1801 -6.8 -28.6 79.4 -20.6 -1.1 -6.4

CCATTTCCTCTGAGCTTTCT 2119 SEQ ID NO:1802 -6.8 -26.3 76.1 -19.5 0 -5.7

CCATCAGCAGGAGAAGAGAT 2151 SEQ ID NO: 1803 -6.8 -23.2 67.5 -16.4 0 -4.1

GTCTGCAACATGAGGTGACT 2287 SEQ ID NO: 1804 -6.8 -23.9 70.2 -16.4 -0.5 -6.4

GTTCTTATTTTTAAAGGGAA 2544 SEQ ID NO: 1805 -6.8 -17.4 55.5 -10.6 0 -4.6

TCTGTGAATGCCTGTGAGAA 2629 SEQ ID NO: 1806 -6.8 -22.8 66.6 -16 0 -3

CTGCCATGAAAGAGAATCCA 2805 SEQ ID NO: 1807 -6.8 -22.2 63 -14.9 -0.1 -4.6

TAGCATTATAAGAACATTTG 3172 SEQ ID NO: 1808 -6.8 -16 52 -9.2 0 -4.1

TCAAACACATTTCATAGAAA 3197 SEQ ID NO:1809 -6.8 -15.7 50.8 -8.2 -0.4 -4.7

GCTGTCAAGTAGTGCGGATC

228 SEQ ID NO: 1810 -6.7 -25.2 73.9 -18.5 0 -4.6 CGCTGTCAAGTAGTGCGGAT

229 SEQ ID NO: 1811 -6.7 -25.6 72.1 -17.6 -1.2 -5.3 TAGAAATACACCAAGGGCTC

251 SEQ ID NO: 1812 -6.7 -21.2 62 -14.5 0 -3.9

CAATTCTGCAACCTGTTTAT 381 SEQ ID NO: 1813 -6.7 -21.4 63.1 -14.7 0 -4.9

TACACCCTCTAATAAGAGTT 633 SEQ ID NO: 1814 -6.7 -20.9 62.2 -12.3 -1.9 -5.2

TCCCAGGTCCTCCATCGCCT 759 SEQ ID NO: 1815 -6.7 -33.8 88.4 -26.4 -0.4 -3.8

TACAACTCTCTCAAACATAT 984 SEQ ID NO:1816 -6.7 -17.9 55.9 -11.2 0 -1.8

TCAAACATCCGGTTCAGCAG 1118 SEQ ID NO: 1817 -6.7 -23.9 67.8 -16.5 -0.5 -6.6

GAGGCAAAGTCCAAGAGCCA 1175 SEQ ID NO: 1818 -6.7 -25.6 71.2 -16.5 -2.4 -6.6

GTCCAGTCTCCAGGCATGGT 1421 SEQ ID NO: 1819 -6.7 -30 86.3 -21.8 -1.4 -9.4

AAGTTTTATCAAATTGCACG 1467 SEQ ID NO: 1820 -6.7 -17.8 55 -10.6 0 -8.1

ATAATGTCTCAACATCTGGT 1819 SEQ ID NO: 1821 -6.7 -20.5 62.7 -12.2 -1.6 -4.7

AACATAATGTCTCAACATCT 1822 SEQ ID NO: 1822 -6.7 -18.3 56.9 -10 -1.6 -6.8

TCATCTATCTGCGACCTGAA 2066 SEQ ID NO: 1823 -6.7 -23.6 67.5 -16.9 0 -4.2

GACAAGTCAAACACGAACGC 2215 SEQ ID NO:1824 -6.7 -20.3 58.2 -13.6 0 -5.5

TGAGAAGAACCCCGAATGGA 2233 SEQ ID NO: 1825 -6.7 -23.1 63 -15.8 -0.3 -3.3

145 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

TAGCATTCCTATGAGAAGAA 2244 SEQ ID NO: 1826 -6.7 -19.7 59.8 -12.3 -0.4 -4.1

AACATGAGGTGACTGTAAGG 2281 SEQ ID NO: 1827 -6.7 -20.3 61.4 -12.7 -0.7 -5.5

AAACATGGTCTGCAACATGA 2294 SEQ ID NO: 1828 -6.7 -20.5 60.5 -11.8 -2 -9.1

AACTTAGCACATTTATAGTA 2362 SEQ ID NO: 1829 -6.7 -18.1 57.4 -11.4 0 -4.1

ATTTAAAACCCACTTTTTAA 2400 SEQ ID NO: 1830 -6.7 -17.2 53.2 -9.4 -1 -5

CAGAAGATTTAAAACCCACT 2406 SEQ ID NO: 1831 -6.7 -19 56.3 -12.3 0 -5

TTGATTAGAAAAGCAGGGAG 2427 SEQ ID NO: 1832 -6.7 -18.5 57 -11.8 4.8 -4.1

GAAGAACATGAGTTTCGTAA 2669 SEQ ID NO: 1833 -6.7 -18.1 56 -10.5 -0.8 -7.3

AATGCTTGTCTTCACTATAG 2907 SEQ ID NO: 1834 -6.7 -20.3 62.9 -13.6 0 -5.5

TATTTTTTGGGGAAAAAGGC 3075 SEQ ID NO: 1835 -6.7 -18.6 56.7 -10.1 -1.8 -7.6

TAAATGTACAAATGACAGCT 3355 SEQ ID NO: 1836 -6.7 -16.9 53 -10.2 0 -6.8

TCGCTGTCAAGTAGTGCGGA

230 SEQ ID NO: 1837 -6.6 -26 73.8 -17.6 -1.8 -6.1 GTCGCTGTCAAGTAGTGCGG

231 SEQ ID NO: 1838 -6.6 -26.6 75.9 -18.2 -1.8 -6.1 CACTCCGACAATTCTGCAAC

389 SEQ ID NO: 1839 -6.6 -23.2 65.3 -16.6 0 -4.9

CTGAGCCTATGCACTCCGAC 400 SEQ ID NO: 1840 -6.6 -27.5 75.1 -19.4 -1.4 -5.8

CCACCAGTTCACTGCCGTAG 700 SEQ ID NO: 1841 -6.6 -28.6 77.7 -21.5 -0.1 -6.4

TGGCCTCGTTCCACCAGTTC 710 SEQ ID NO: 1842 -6.6 -30.1 82.8 -23 -0.2 -7.2

GGAGGCTTGGGCTTCCGTCT 788 SEQ ID NO: 1843 -6.6 -30.7 85.3 -20.6 -3.5 -9.7

GGGCAAGGATTGACTGTATT 929 SEQ ID NO: 1844 -6.6 -22.8 67.1 -14.9 -1.2 -5

GAAAAATCCGATTTTAGCTC 1026 SEQ ID NO: 1845 -6.6 -18.7 56.4 -10.8 -1.2 -9.3

GCATCGGGGCCCCAACATGG 1447 SEQ ID NO: 1846 -6.6 -31.2 79.5 -21.7 -0.4 -13.9

CAAGTTTTATCAAATTGCAC 1468 SEQ ID NO: 1847 -6.6 -17.7 55.5 -10.4 -0.3 -8.1

TGTGTAACCAGCCGTCTTTG 1606 SEQ ID NO: 1848 -6.6 -25.6 72.2 -18.5 -0.1 -3.3

GCTTCCTTCCCTACACTTGC 2197 SEQ ID NO: 1849 -6.6 -29.1 81 -22.5 0 -2.8

TGACTGTAAGGCGGTGTTCT 2272 SEQ ID NO: 1850 -6.6 -24.7 71.8 -17.4 -0.4 -5.2

AACTGAGGAAGTCTCAAATA 2381 SEQ ID NO: 1851 -6.6 -18 56.1 -9.6 -1.8 -6.2

GCAAAGTCCTAACCCCTTGA 2443 SEQ ID NO: 1852 -6.6 -26.4 71.3 -19.8 0 -3.4

TGCCTGTGAGAAGGGACAGT 2621 SEQ ID NO: 1853 -6.6 -25.5 73.2 -17.6 -1.2 -5.8

GTTCTGAGTTGGATCTGCCC 2739 SEQ ID NO: 1854 -6.6 -27.4 79.3 -20.3 -0.2 -5

GAAATGCTTGCCTGAGAGTT 3095 SEQ ID NO: 1855 -6.6 -23.2 67.3 -16.6 0 -3.2

TTTCCAGATTTCTACATCCT 3231 SEQ ID NO:1856 -6.6 -23.3 69 -16.7 0 -2.9

146 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTGGAGAAGTGAATCCCAGG 3259 SEQ ID NO: 1857 -6.6 -24 68.1 -15.7 -1.7 -6.2

AATATTTATTTTGGTTTCCT 3605 SEQ ID NO: 1858 -6.6 -19.1 59.5 -12.5 0 -3.8

ATCATAGAAATACACCAAGG 255 SEQ ID NO: 1859 -6.5 -18 55.2 -11.5 0 -3.6

TGCACTCCGACAATTCTGCA 391 SEQ ID NO: 1860 -6.5 -25.5 70.6 -17.8 -1.1 -4.7

GCCTGGTATTAACTTATTTT 654 SEQ ID NO: 1861 -6.5 -21.1 63.6 -14.6 0.6 -4.7

CAACTATGATTTTAAGGCCT 670 SEQ ID NO: 1862 -6.5 -20.6 61 -13.5 0 -8.4

TCGGTGAGTGACCATTGCTC 867 SEQ ID NO: 1863 -6.5 -26.1 74.7 -17.9 -1.7 -6.2

TGGGCAAGGATTGACTGTAT 930 SEQ ID NO: 1864 -6.5 -22.7 66.6 -14.9 -1.2 -5

GCGAGAGGCAAGAAAGATAT 962 SEQ ID NO: 1865 -6.5 -20.3 59.7 -12.9 -0.7 -4.2

AGCTTCTGCTGTTTTCGCTG 1581 SEQ ID NO: 1866 -6.5 -26.2 76.5 -18.3 -1.3 -6.3

CACCATATCTTCGAGGATAG 1911 SEQ ID NO: 1867 -6.5 -22 64.5 -14.6 -0.4 -9.4

CTTCTTCACACTAAACCTTG 2101 SEQ ID NO: 1868 -6.5 -21 62.4 -14.5 0 -1.9

CATTTCCTCTGAGCTTTCTT 2118 SEQ ID NO: 1869 -6.5 -24.4 72.8 -17.9 0 -5.7

GTGCCATTTCCTCTGAGCTT 2122 SEQ ID NO: 1870 -6.5 -27.9 79.9 -20.9 -0.2 -5.7

ATGGTCTGCAACATGAGGTG 2290 SEQ ID NO:1871 -6.5 -23.4 68.8 -16.3 -0.3 -6

AAATAACTTAGCACATTTAT 2366 SEQ ID NO: 1872 -6.5 -15.8 51.3 -9.3 0 -4.1

AGTCTCAAATAACTTAGCAC 2372 SEQ ID NO: 1873 -6.5 -18.8 58.6 -12.3 0 -4.1

CTCTGGTCCGCTTGTGAGAT 2582 SEQ ID NO: 1874 -6.5 -27 76.9 -19.8 -0.4 -4.5

TATCTGCATGGTTCTGAGTT 2749 SEQ ID NO: 1875 -6.5 -23.2 70.7 -16.7 0 -5

TAAGTACTCAAGTATATACT 3132 SEQ ID NO: 1876 -6.5 -16.8 54.7 -9.6 0 -9

CATTTGCTTATTACTGTCCA 3158 SEQ ID NO: 1877 -6.5 -22.6 67.2 -16.1 0 -3

GAACATTTGCTTATTACTGT 3161 SEQ ID NO:1878 -6.5 -19.6 60.4 -13.1 0 -3.6

AACTTTCCAGATTTCTACAT 3234 SEQ ID NO: 1879 -6.5 -20.4 62 -13.9 0 -3.1

CAATTCAGTCAAATGTGGCA 3335 SEQ ID NO: 1880 -6.5 -21 62.4 -13.4 -1 -4

AATTATTGACTTTTTGTGCA 3499 SEQ ID NO: 1881 -6.5 -19 59.1 -12.5 0 -5.2

AGCGTGTTGGTCGGAAGAGT 83 SEQ ID NO: 1882 -6.4 -25.6 73.3 -18.4 -0.6 -5

AGGGCTCGTCGCTGTCAAGT 238 SEQ ID NO: 1883 -6.4 -28.2 79.6 -20.8 -0.9 -5.1

ATGTTGTGACATCATCATAG 268 SEQ ID NO: 1884 -6.4 -19.9 62 -12.2 -1.2 -5.7

CACTCTACAACTCTCTCAAA 989 SEQ ID NO: 1885 -6.4 -20.4 61.6 -14 0 0

AGCAGCCTGATATCTCCTTG 1046 SEQ ID NO: 1886 -6.4 -26.2 75.2 -19.8 0 -6.4

TTGGAACCACGGGGAAGACA 1096 SEQ ID NO: 1887 -6.4 -24.1 66.1 -16.9 -0.6 -6.5

147 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CATCGGGGCCCCAACATGGC

1446 SEQ ID NO: 1888 -6.4 -31.2 79.5 -21.7 -1.3 -14.4 TATCAAATTGCACGGCATCG

1461 SEQ ID NO: 1889 -6.4 -21.9 62 -14.6 -0.8 -7.3 TTCTGCACAGTTCCTCAAAC

1873 SEQ ID NO: 1890 -6.4 -23.3 68.4 -16.4 -0.2 -5.2 TTCCGCAGCTCTGGCCTTTT

2042 SEQ ID NO: 1891 -6.4 -30 82.2 -22.6 -0.9 -7.2 ACACTAAACCTTGATAGTGG

2094 SEQ ID NO: 1892 -6.4 -20.2 60.4 -11.2 -2.6 -7.3 CTGTATTCAAAATTAACAAC

2178 SEQ ID NO: 1893 -6.4 -14.4 48.2 -8 0 -4.2 CCTTCCCTACACTTGCTGTA

2193 SEQ ID NO: 1894 -6.4 -27.7 77.2 -20.6 -0.4 -3.9 CCCGAATGGACAAGTCAAAC

2223 SEQ ID NO: 1895 -6.4 -21.8 61 -14.8 -0.3 -6.1 CTTAGCACATTTATAGTATC

2360 SEQ ID NO: 1896 -6.4 -19 60.3 -12.6 0 -4.1 CTTTTTAAACTGAGGAAGTC

2388 SEQ ID NO: 1897 -6.4 -18 56.8 -10.9 -0.5 -4.4 ACCCCTTGATTAGAAAAGCA

2432 SEQ ID NO: 1898 -6.4 -22.6 63.6 -16.2 0.6 -4.1 TCTTATTTTTAAAGGGAACA

2542 SEQ ID NO: 1899 -6.4 -17 54.1 -10.6 0 -4.6 CTGTGAATGCCTGTGAGAAG

2628 SEQ ID NO: 1900 -6.4 -22.4 65.4 -16 0 -3 GAGAAGAACATGAGTTTCGT

2671 SEQ ID NO: 1901 -6.4 -19.7 59.9 -12.3 -0.9 -7.3 GCCCTCCCGCTTACTGGAAA

2723 SEQ ID NO: 1902 -6.4 -29.9 77 -23.5 0 -3.5 AATTTTGGCTTGTCAAACAC

3209 SEQ ID NO: 1903 -6.4 -19.6 59.4 -10.3 -2.9 -7.3 TCCAGATTTCTACATCCTAG

3229 SEQ ID NO: 1904 -6.4 -22.8 67.9 -16.4 0 -3.2 CATATATGAAGTTAGGCTAC

3469 SEQ ID NO: 1905 -6.4 -18.8 58.8 -11.9 0 -7.7 TTGGTTTATAAAACATAGAA

3562 SEQ ID NO: 1906 -6.4 -14.5 48.6 -6.2 -1.9 -4.4 TAAGCGTGTTGGTCGGAAGA

85 SEQ ID NO: 1907 -6.3 -23.4 66.9 -16.4 -0.4 -4.9 CTATGTACGTGATGGCTTCA

562 SEQ ID NO: 1908 -6.3 -23.4 68.5 -16.4 -0.2 -8.6 CAGTTCACTGCCGTAGGCAT

696 SEQ ID NO: 1909 -6.3 -27.4 76.9 -16.6 -4.5 -11.1 GGGCGAGAGGCAAGAAAGAT

964 SEQ ID NO: 1910 -6.3 -23 65 -15.1 -1.5 -4 CCAAGAGCCATCGCTTCAGC

1165 SEQ ID NO: 1911 -6.3 -28 76.3 -20.7 -0.9 -4.9 TGCTGTTTTCGCTGGGTCCT

1575 SEQ ID NO: 1912 -6.3 -29 81.8 -21.6 -1 -4.9 CCGTCTTTGTCCAAAGCTTC

1595 SEQ ID NO: 1913 -6.3 -25.6 72.3 -18.4 -0.7 -8.4 ACCCTTCAAATCCTCTCTTT

1852 SEQ ID NO: 1914 -6.3 -25 71 -18.7 0 -1.6 CACACTAAACCTTGATAGTG

2095 SEQ ID NO: 1915 -6.3 -19.7 59.1 -11.2 -2.2 -6.8 GATTTAAAACCCACTTTTTA

2401 SEQ ID NO: 1916 -6.3 -18.5 56.1 -12.2 0 -5 TTAGAAAAGCAGGGAGACAG

2423 SEQ ID NO: 1917 -6.3 -19.3 58.6 -13 0 -4.1 AGAAGAACATGAGTTTCGTA

2670 SEQ ID NO: 1918 -6.3 -18.8 58 -11.5 -0.9 -6.2

148 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTCCTTATCTGCATGGTTCT 2754 SEQ ID NO: 1919 -6.3 -25.6 75.4 -19.3 0 -5

GATCTTTTGATATGAAAACC 3039 SEQ ID NO:1920 -6.3 -17.2 53.9 -9.8 -1 -4.1

ATCCCAACATGATCTTTTGA 3049 SEQ ID NO: 1921 -6.3 -22.1 64.3 -15.8 0 -5.2

GTAGCATTATAAGAACATTT 3173 SEQ ID NO: 1922 -6.3 -17.2 54.9 -10.9 0 -4.4

ACACTTAAAGCAAACATTCA 3535 SEQ ID NO:1923 -6.3 -17.6 54.4 -11.3 0 -4.1

GGCTCGTCGCTGTCAAGTAG 236 SEQ ID NO:1924 -6.2 -26.7 76.3 -19.5 -0.9 -5.1

TTCCCCTCTGGAAACCTTCG 292 SEQ ID NO: 1925 -6.2 -27.5 73.1 -19.7 -1.5 -5.4

TAGGGTTGGTCTGGTTTCCG 347 SEQ ID NO: 1926 -6.2 -26.9 77.7 -20.1 -0.3 -3.6

GCCAATGAACTGATCTGGGG 447 SEQ ID NO:1927 -6.2 -24.3 68.2 -17.3 -0.6 -4.9

TATTTTGAGCAAAGATGCCA 463 SEQ ID NO:1928 -6.2 -20.8 61.4 -12.4 -2.2 -6.9

CAATAATCACCCACTCAGGT 484 SEQ ID NO: 1929 -6.2 -23.6 67 -16.9 -0.1 -3.6

GTTCAATAATCACCCACTCA 487 SEQ ID NO: 1930 -6.2 -22.9 66.1 -16.7 0 -1.6

AGCTGAACAATCGCTCACTA 891 SEQ ID NO: 1931 -6.2 -22.6 65.2 -14.7 -1.7 -4.9

TTGCTTTCACAAAAGCTGAA 904 SEQ ID NO: 1932 -6.2 -19.5 58.5 -9.2 -4.1 -9.2

ACACTCTACAACTCTCTCAA

990 SEQ ID NO: 1933 -6.2 -21.3 64.3 -15.1 0 -0.2 CACACTCTACAACTCTCTCA

991 SEQ ID NO:1934 -6.2 -22.7 67.8 -16.5 0 -0.2 TGTCCGTATCCTTCATAAAA

1373 SEQ ID NO:1935 -6.2 -21.4 62.2 -15.2 0 -2.6

CTTTCTCCGTGGACAAACAC 1769 SEQ ID NO:1936 -6.2 -23.2 66 -16.5 -0.2 -5.4

AACGACCCTTCAAATCCTCT 1856 SEQ ID NO: 1937 -6.2 -24.4 66.8 -18.2 0 -3.5

TGACATCCTTATTTCTGCAC 1885 SEQ ID NO:1938 -6.2 -22.8 67.6 -16.6 0 -4.8

TAAACCTTGATAGTGGAATA 2090 SEQ ID NO:1939 -6.2 -17.8 55.1 -11.6 0 -3.3

GGAGAAGAGATTGTGGAACT 2142 SEQ ID NO:1940 -6.2 -20.4 61.6 -13.5 -0.5 -4

ACAAGTCAAACACGAACGCT 2214 SEQ ID NO: 1941 -6.2 -20.6 58.8 -14.4 0 -4.6

TGGACAAGTCAAACACGAAC 2217 SEQ ID NO: 1942 -6.2 -18.9 56.3 -12.7 0 -6.1

TAAACATGGTCTGCAACATG 2295 SEQ ID NO:1943 -6.2 -19.6 58.7 -11.8 -1.6 -8.6

TATTTTTAAAGGGAACACTT

2539 SEQ ID NO: 1944 -6.2 -16.8 53.4 -10.6 0 -4.6 TTATTTTTAAAGGGAACACT

2540 SEQ ID NO: 1945 -6.2 -16.8 53.4 -10.6 0 -4.3 CTTATTTTTAAAGGGAACAC

2541 SEQ ID NO: 1946 -6.2 -16.8 53.4 -10.6 0 -4.6 GATCTCTGGTCCGCTTGTGA

2585 SEQ ID NO: 1947 -6.2 -27.4 78.4 -20.5 -0.4 -4.7

TATTCAGGCGTCACAGCTGA

2957 SEQ ID NO: 1948 -6.2 -25.2 72.9 -17.8 -1.1 -9.1

TGAAGATAAAGTAGACAGTT

2976 SEQ ID NO:1949 -6.2 -16.5 53.4 -10.3 0 -2.9

149 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

ATCTTTTGATATGAAAACCA 3038 SEQ ID NO:1950 -6.2 -17.3 53.9 -10.4 -0.4 -3.4

TCCATTTCAATAAGTACTCA 3142 SEQ ID NO: 1951 -6.2 -19.8 60.6 -13.6 0 -6.2

ATTACTGTCCATTTCAATAA 3149 SEQ ID NO: 1952 -6.2 -18.8 58.1 -12.6 0 -3

CTTGTCAAACACATTTCATA 3201 SEQ ID NO: 1953 -6.2 -18.7 57.9 -12 -0.1 -3.7

CATCCTAGAATTTTGGCTTG 3217 SEQ ID NO: 1954 -6.2 -21.9 64.7 -15.7 0 -3.8

CCAAATTAACTTTAAAAAAT 3281 SEQ ID NO: 1955 -6.2 -11.9 42.8 -5.7 0 -4.3

GTGAACTGCTGTTAATTTCC 3300 SEQ ID NO: 1956 -6.2 -21.8 65 -14.7 -0.7 -7.7

AAAACATAGAAATAGCCAAC 3553 SEQ ID NO: 1957 -6.2 -15.4 49.3 -9.2 0 -3.2

CGGAAGTCAACCAGCTCTGG 50 SEQ ID NO: 1958 -6.1 -25.6 71.1 -18.6 -0.8 -8.3

GAAAGCCATTCATAGGGTTG 359 SEQ ID NO: 1959 -6.1 -22.3 65.3 -14.6 -1.5 -4.7

CTACACCCTCTAATAAGAGT 634 SEQ ID NO: 1960 -6.1 -21.7 63.8 -13.7 -1.9 -5.2

CTACAACTCTCTCAAACATA 985 SEQ ID NO: 1961 -6.1 -18.8 57.8 -12.7 0 -0.7

GAAAATTCGGTCAAACATCC 1128 SEQ ID NO: 1962 -6.1 -19.2 56.8 -13.1 0 -4.1

TTGTCCGAAAATTCGGTCAA 1134 SEQ ID NO: 1963 -6.1 -21.1 60.4 -12.2 -2.8 -11.7

ACTCTGTCTGTCCGTATCCT 1381 SEQ ID NO: 1964 -6.1 -27.5 79.4 -21.4 0 -2.6

CTCCAGGCATGGTTAGGCAG 1414 SEQ ID NO: 1965 -6.1 -27.6 78.7 -20 -1.4 -9.4

TTTGTCCAAAGCTTCTGCTG 1590 SEQ ID NO: 1966 -6.1 -23.9 69.6 -16.1 -1.7 -7.1

TCAACATCTGGTACCACAAT 1811 SEQ ID NO: 1967 -6.1 -21.8 63.6 -14.8 0 -9.6

CTTATTTCTGCACAGTTCCT 1878 SEQ ID NO: 1968 -6.1 -24.2 71.9 -18.1 0 -4.9

ATAGTTCCGCAGCTCTGGCC 2046 SEQ ID NO: 1969 -6.1 -29.7 82.4 -22.6 -0.9 -6.2

TAAACTGAGGAAGTCTCAAA 2383 SEQ ID NO: 1970 -6.1 -17.3 54.3 -9.6 -1.6 -4.8

AGAAGATTTAAAACCCACTT 2405 SEQ ID NO: 1971 -6.1 -18.4 55.5 -12.3 0 -5

CCGCTTACTGGAAACCTTAT 2717 SEQ ID NO: 1972 -6.1 -23.7 65.6 -17.6 0 -3.3

GCAGATTTTTAAATAACCCC 2879 SEQ ID NO: 1973 -6.1 -21 60.6 -14.3 -0.3 -4.5

TCCAGGTAACTCTTTCTTGA 2927 SEQ ID NO: 1974 -6.1 -23.1 69.2 -16.1 -0.8 -3.6

AAGTACTCAAGTATATACTC 3131 SEQ ID NO: 1975 -6.1 -17.5 56.7 -10.6 -0.2 -9.2

TGTGCTTGTATATAATACAT 3405 SEQ ID NO: 1976 -6.1 -18.2 57.4 -10.5 -1.5 -6.8

TGTTATTACAATGACAATTC 3442 SEQ ID NO: 1977 -6.1 -16.3 52.8 -9.7 -0.1 -5.6

AAAGCAAACATTCAAAACCC 3529 SEQ ID NO: 1978 -6.1 -17.9 53.3 -11.8 0 -4.1

GGAAGTCAACCAGCTCTGGC 49 SEQ ID NO: 1979 -6 -26.6 75.4 -19.5 -1 -8.6

ACCACCACTACCCGCCACTT 201 SEQ ID NO: 1980 -6 -31.3 79.1 -25.3 0 -2.6

150 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

ACCTTCGTATAATGTTGTGA 279 SEQ ID NO: 1981 -6 -21.4 63.6 -15.4 0 -2.4

GAGCCTAAACAAGGGCCATT 326 SEQ ID NO: 1982 -6 -24.8 68.3 -16.9 -1.9 -7.8

GTCTATTTTGAGCAAAGATG 466 SEQ ID NO: 1983 -6 -18.8 58.6 -12.8 0 -5.9

TCTTCCCAGGTCCTCCATCG 762 SEQ ID NO: 1984 -6 -30.5 83 -23.2 -1.2 -4.5

GGGGTTGCCTGTAGTTCCAC 843 SEQ ID NO: 1985 -6 -29.1 83.2 -22 -1 -4.6

CGAGAGGCAAGAAAGATATC 961 SEQ ID NO: 1986 -6 -18.9 57.1 -12.9 0 -5.6

AGCCATCGCTTCAGCGTGGT 1160 SEQ ID NO: 1987 -6 -29.8 81.6 -20 -3.8 -13.6

GGCAAAGTCCAAGAGCCATC 1173 SEQ ID NO: 1988 -6 -25.4 71.2 -17.8 -1.6 -6

GGAAGATCAGCCGGTCCCAC 1246 SEQ ID NO: 1989 -6 -29.1 77.9 -23.1 0 -6.7

CTCCTGTCACCATCAGCCGG 1297 SEQ ID NO: 1990 -6 -30.3 81.3 -23.7 -0.2 -8.2

GAAGGCCATTGTCGATAGAA 2002 SEQ ID NO: 1991 -6 -22.3 64.1 -15 -1.1 -9.7

ATGAGGTGACTGTAAGGCGG 2278 SEQ ID NO: 1992 -6 -23.9 68.8 -17 -0.7 -5.2

GTCTCAAATAACTTAGCACA 2371 SEQ ID NO: 1993 -6 -19.5 59.6 -13.5 0 -4.1

CTTGATTAGAAAAGCAGGGA 2428 SEQ ID NO: 1994 -6 -19.4 58.6 -13.4 4.8 -4.1

GCGTCACAGCTGAGCATGGC 2950 SEQ ID NO: 1995 -6 -28.6 80 -21.2 -1.3 -9.1

CAAACACATTTCATAGAAAT 3196 SEQ ID NO: 1996 -6 -15.3 49.7 -8.2 -1 -5.9

TTTTGGTTTCCTTCATTGTT 3597 SEQ ID NO: 1997 -6 -22.8 69.4 -16.8 0 -3.2

CTGCAACCTGTTTATATGAA 376 SEQ ID NO: 1998 -5.9 -20.5 60.8 -14.6 0 -4.9

GAACTGATCTGGGGCAGTCT 441 SEQ ID NO: 1999 -5.9 -25.5 74.2 ¹ -18 -1.5 -5.4

AACAAAAACCAGAGAGAGTT 594 SEQ ID NO:2000 -5.9 -17.4 53.7 -11.5 0 -3.3

TCTACAACTCTCTCAAACAT 986 SEQ ID NO:2001 -5.9 -19.5 59.7 -13.6 0 -0.3

TCGGTCAAACATCCGGTTCA 1122 SEQ ID NO:2002 -5.9 -25 69.4 -17.4 -1.7 -6.6

CAGACACCGGGGCGGCTCCT 1312 SEQ ID NO:2003 -5.9 -32.6 83.3 -25 -1.7 -9.6

AGTCTCCAGGCATGGTTAGG 1417 SEQ ID NO:2004 -5.9 -26.7 78.5 -19.9 -0.8 -8.8

CGGGGCCCCAACATGGCCTG 1443 SEQ ID NO:2005 -5.9 -33 81.7 -23.2 -3.9 -14.4

AAAATAATTCAGGGTGCAAT 1984 SEQ ID NO:2006 -5.9 -17.5 54.1 -11.6 0 -5.4

AACCCCGAATGGACAAGTCA 2226 SEQ ID NO:2007 -5.9 -24.5 66.1 -18 -0.3 -6.1

AGAAGAACCCCGAATGGACA 2231 SEQ ID NO:2008 -5.9 -23.4 63.5 -16.9 -0.3 -3.3

ATTCCTATGAGAAGAACCCC 2240 SEQ ID NO:2009 -5.9 -23.7 66.3 -17.8 0 -3.1

CTGGAGAACCGAGTCCAAGA 2830 SEQ ID NO:2010 -5.9 -24.4 67.8 -17.2 -1.2 -5.8

GAAGATAAAGTAGACAGTTA 2975 SEQ ID NO: 2011 -5.9 -16.2 52.9 -10.3 0 -2.9

151 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo AGTATATACTCCCTTAATAG

3122 SEQ ID NO: 2012 -5.9 -19.5 60 -13 0 -8.5 TACTCAAGTATATACTCCCT

3128 SEQ ID NO: 2013 -5.9 -21.9 65.3 -15.2 0 -9.2 CATTTCAATAAGTACTCAAG

3140 SEQ ID NO: 2014 -5.9 -16.7 53.7 -10.8 0 -6.2 AGAATTTTGGCTTGTCAAAC

3211 SEQ ID NO: 2015 -5.9 -19.3 59.2 -10.8 -2.6 -7.9 TTAAATGTACAAATGACAGC

3356 SEQ ID NO: 2016 -5.9 -16.1 51.5 -10.2 0 -6.3 CCAAAACAGCTGCTTTAAAT

3370 SEQ ID NO: 2017 -5.9 -19.4 57.1 -12.8 0 -9.1 AGAAATAGCCAACACTTAAA

3546 SEQ ID NO: 2018 -5.9 -17.1 52.8 -11.2 0 -3.2 AACCAGCTCTGGCATTCGAA

42 SEQ ID NO: 2019 -5.8 -25.1 69.6 -18.2 -1 -8.7 TCTGGTTTCCGAGAGCCTAA

338 SEQ ID NO:2020 -5.8 -26 73.1 -19.7 -0.2 -4.7 CCGACAATTCTGCAACCTGT

385 SEQ ID NO: 2021 -5.8 -25.1 68.5 -19.3 0 -4.9 CCCAGGTCCTCCATCGCCTT

758 SEQ ID NO: 2022 -5.8 -33.5 86.9 -26.4 -1.2 -4.6 GCTGCGAAGCTCTGCTTCTT

1203 SEQ ID NO: 2023 -5.8 -27.4 77.6 -18.4 -3.2 -10.4 GGCAGTGCACTCTGTCTGTC

1389 SEQ ID NO: 2024 -5.8 -27.9 83.8 -20.8 -0.8 -10.2 GTTTTATCAAATTGCACGGC

1465 SEQ ID NO: 2025 -5.8 -21.5 63 -15.2 0 -8.1 AGTTTTATCAAATTGCACGG

1466 SEQ ID NO: 2026 -5.8 -19.7 59.2 -13.4 0 -8.1 ACAAGTTTTATCAAATTGCA

1469 SEQ ID NO: 2027 -5.8 -17.7 55.5 -10.6 -1.2 -6.4 TTCTCCGTGGACAAACACCT

1767 SEQ ID NO: 2028 -5.8 -25.1 69.1 -18.5 -0.6 -5.6 TAGAAAATAATTCAGGGTGC

1987 SEQ ID NO: 2029 -5.8 -17.8 55.5 -10.5 -1.4 -4.5 CACTAAACCTTGATAGTGGA

2093 SEQ ID NO: 2030 -5.8 -20.6 61.1 -13.1 -1.7 -5.8 GCAGGAGAAGAGATTGTGGA

2145 SEQ ID NO: 2031 -5.8 -22.5 67 -16.7 0 -3.4 AGAACCCCGAATGGACAAGT

2228 SEQ ID NO: 2032 -5.8 -24 65.1 -17.6 -0.3 -3.3 ATGAGAAGAACCCCGAATGG

2234 SEQ ID NO: 2033 -5.8 -22.5 61.9 -16.7 0 -3.1 ATAAACATGGTCTGCAACAT

2296 SEQ ID NO: 2034 -5.8 -19.6 58.8 -13.2 -0.3 -6 ACTTTTTAAACTGAGGAAGT

2389 SEQ ID NO: 2035 -5.8 -17.8 56 -11.4 -0.3 -4.6 TTCTTATTTTTAAAGGGAAC

2543 SEQ ID NO:2036 -5.8 -16.4 53.2 -10.6 0 -5.7 TGTGAATGCCTGTGAGAAGG

2627 SEQ ID NO: 2037 -5.8 -22.7 66 -16.4 -0.2 -3.5 AATCCCAACATGATCTTTTG

3050 SEQ ID NO:2038 -5.8 -20.8 61.1 -15 0 -5.2 ATTTTTTGGGGAAAAAGGCA

3074 SEQ ID NO: 2039 -5.8 -19.6 58.4 -12 -1.8 -8.5 ATTTGCTTATTACTGTCCAT

3157 SEQ ID NO: 2040 -5.8 -21.9 66 -16.1 0 -3.6 GAAATGAACTTTCCAGATTT

3240 SEQ ID NO: 2041 -5.8 -18.3 56.2 -11.8 -0.5 -3.8 GGTGACAAATTATTGACTTT

3506 SEQ ID NO: 2042 -5.8 -18.3 56.9 -11.8 -0.5 -3.9

152 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo ACATAGAAATAGCCAACACT

3550 SEQ ID NO: 2043 -5.8 -19.3 57.6 -13.5 0 -3.2 CAAGGGCTCGTCGCTGTCAA

240 SEQ ID NO: 2044 -5.7 -27 74.4 -20.8 -0.1 -4.5 GAGAGCCTAAACAAGGGCCA

328 SEQ ID NO: 2045 -5.7 -25.3 69.5 -17.7 -1.9 -7.6 GTTGGTCTGGTTTCCGAGAG

343 SEQ ID NO: 2046 -5.7 -26 76 -19.7 -0.3 -3.8 AGAGAGTTCAGCTTTGTTGA

582 SEQ ID NO: 2047 -5.7 -22.4 69.4 -16.1 -0.3 -4.7 TTATCAAATTGCACGGCATC

1462 SEQ ID NO: 2048 -5.7 -21.2 61.9 -14.6 -0.8 -7.3 AGAATCCTTCCCAAGTCTCA

1929 SEQ ID NO: 2049 -5.7 -25.3 72.1 -19.1 -0.1 -2.8 TAGAGGTCATCTATCTGCGA

2072 SEQ ID NO: 2050 -5.7 -23.3 69.5 -16.9 -0.5 -6.3 GAGCTTTCTTCTTCACACTA

2108 SEQ ID NO: 2051 -5.7 -23.1 70.5 -17.4 0 -5.2 TGTGCCATTTCCTCTGAGCT

2123 SEQ ID NO: 2052 -5.7 -27.8 79.3 -21.6 -0.2 -5.7 TTGTGGAACTGTGCCATTTC

2132 SEQ ID NO: 2053 -5.7 -23.8 69.6 -17.3 -0.6 -4.9 CCCCTTGATTAGAAAAGCAG

2431 SEQ ID NO: 2054 -5.7 -22.4 63.3 -16.7 0.6 -4.1 CCTCTAGTGCACTGTACTCT

2518 SEQ ID NO: 2055 -5.7 -26 76.8 -19.1 0.1 -10.3 ATGCCTGTGAGAAGGGACAG

2622 SEQ ID NO: 2056 -5.7 -24.3 69.8 -17.6 -0.9 -5.7 CAGAGGCTCCTTATCTGCAT

2760 SEQ ID NO: 2057 -5.7 -26.1 75.5 -19.6 -0.6 -5.1 GATGGAGTCGGGGAATCAGG

2851 SEQ ID NO: 2058 -5.7 -24.6 70.3 -17.9 -0.9 -4.7 AACCCCTGAAAAAGGATGGA

2865 SEQ ID NO: 2059 -5.7 -21.8 60.5 -14.9 -1.1 -4.9 ATTTCAATAAGTACTCAAGT

3139 SEQ ID NO: 2060 -5.7 -17.2 55.3 -11.5 0 -6.2 AATGAACTTTCCAGATTTCT

3238 SEQ ID NO:2061 -5.7 -19.7 60 -14 0 -3.1 AAAAAATCCCTGGAGAAGTG

3268 SEQ ID NO: 2062 -5.7 -18.7 55.6 -13 0 -4.8 TCAGTCAAATGTGGCAAAGA

3331 SEQ ID NO: 2063 -5.7 -20.1 60.4 -13.3 -1 -4.2 AAGCAAACATTCAAAACCCC

3528 SEQ ID NO: 2064 -5.7 -20.6 58.2 -14.9 0 -4.1 AGCTCATGGGCTTGCATTGT

11 SEQ ID NO: 2065 -5.6 -26.8 77.7 -19.5 -1.5 -10.8 GCACCACCACTACCCGCCAC

203 SEQ ID NO: 2066 -5.6 -32.8 81.8 -27.2 0 -3.4 TCCGACAATTCTGCAACCTG

386 SEQ ID NO: 2067 -5.6 -24.3 66.9 -18.7 0 -4.9 ATGCACTCCGACAATTCTGC

392 SEQ ID NO: 2068 -5.6 -24.8 69.5 -19.2 0 -5.5 TGATTTTAAGGCCTGGTATT

664 SEQ ID NO: 2069 -5.6 -22 65.3 -15.7 0 -8.7 CTTCCACCCCACACCTCTGG

727 SEQ ID NO: 2070 -5.6 -31.5 82.2 -25.9 0 -3.3 TTACACACTCTACAACTCTC

994 SEQ ID NO: 2071 -5.6 -20.7 63.4 -15.1 0 -0.6 GCAGTGCACTCTGTCTGTCC

1388 SEQ ID NO: 2072 -5.6 -28.7 84.8 -21.9 -0.5 -10.2 ACATCCTTATTTCTGCACAG

1883 SEQ ID NO: 2073 -5.6 -22.9 67.9 -17.3 0 -4.8

153 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTTCCCAAGTCTCACCATAT 1923 SEQ ID NO: 2074 -5.6 -25.6 72.3 -20 0 -2

CATCTATCTGCGACCTGAAA 2065 SEQ ID NO:2075 -5.6 -22.5 64 -16.9 0 -4.2

TACACTTGCTGTATTCAAAA 2186 SEQ ID NO: 2076 -5.6 -18.5 57.1 -12.2 -0.4 -3.9

GGTCCGCTTGTGAGATTCTC 2578 SEQ ID NO:2077 -5.6 -26.6 77.3 -20.3 -0.4 -7.3

CTACATCCTAGAATTTTGGC 3220 SEQ ID NO:2078 -5.6 -21.7 64.5 -16.1 0 -3.8

ATGAACTTTCCAGATTTCTA 3237 SEQ ID NO:2079 -5.6 -20.1 61.5 -14.5 0 -3.1

ATAAGCGTGTTGGTCGGAAG 86 SEQ ID NO:2080 -5.5 -22.8 65.6 -17.3 0 -4.1

CACTACCCGCCACTTCCACT 196 SEQ ID NO:2081 -5.5 -30.4 78.8 -24.9 0 -2.6

GAGTTCAGCTTTGTTGACTA 579 SEQ ID NO:2082 -5.5 -22.6 69.5 -16.6 -0.1 -4.5

ATTGACTGTATTCTCTGTTG 921 SEQ ID NO: 2083 -5.5 -20.7 64.7 -15.2 0 -3.3

TTGTTTCTGATGATGCCGCT 1220 SEQ ID NO: 2084 -5.5 -25.3 71.8 -19.8 0 -4.7

CCAGTCTCCAGGCATGGTTA 1419 SEQ ID NO:2085 -5.5 -28.2 80.3 -21.2 -1.4 -9.4

GGGCCCCAACATGGCCTGCG 1441 SEQ ID NO:2086 -5.5 -33.6 83.3 -24.2 -3.9 -12.6

GTGTGTAACCAGCCGTCTTT 1607 SEQ ID NO:2087 -5.5 -26.8 75.7 -20.8 -0.1 -3.3

TGGTACCACAATTGCAATGA 1803 SEQ ID NO:2088 -5.5 -21.7 62.7 -15.3 0 -9.5

ACATCTGGTACCACAATTGC 1808 SEQ ID NO:2089 -5.5 -23.3 67.4 -17 0 -9.4

GTCTCAACATCTGGTACCAC 1814 SEQ ID NO:2090 -5.5 -24.3 71.4 -17.9 0 -9.6

TCAGCAGGAGAAGAGATTGT 2148 SEQ ID NO:2091 -5.5 -21.8 66.1 -16.3 0 -4.1

GAAGAACCCCGAATGGACAA 2230 SEQ ID NO:2092 -5.5 -22.7 61.6 -16.6 -0.3 -3.3

CTATGAGAAGAACCCCGAAT 2236 SEQ ID NO:2093 -5.5 -21.9 60.9 -16.4 0 -2.8

GAAGTCTCAAATAACTTAGC 2374 SEQ ID NO:2094 -5.5 -17.8 56.1 -11.4 -0.8 -4.2

TTCCCTCTAGTGCACTGTAC 2521 SEQ ID NO:2095 -5.5 -26.3 76.9 -19.5 0 -10.6

TGAGTTTCGTAACCCTTACG 2661 SEQ ID NO:2096 -5.5 -23.3 65.8 -15.4 -2.4 -7.1

CATGAAAGAGAATCCACGCG 2801 SEQ ID NO:2097 -5.5 -21.1 59.4 -15.1 -0.1 -7.5

ATGCTTGTCTTCACTATAGA 2906 SEQ ID NO:2098 -5.5 -21.6 66.6 -16.1 0 -6

TCAGGCGTCACAGCTGAGCA 2954 SEQ ID NO:2099 -5.5 -27.9 79 -20.3 -2.1 -9.2

TCAGTGAAGATAAAGTAGAC 2980 SEQ ID NO:2100 -5.5 -16.8 54.3 -11.3 0 -5.3

TAATCCCAACATGATCTTTT

3051 SEQ ID NO:2101 -5.5 -20.5 60.6 -15 0 -5.2 TTAATCCCAACATGATCTTT

3052 SEQ ID NO: 2102 -5.5 -20.5 60.6 -15 0 -5.2 AAATGTACAAATGACAGCTC

3354 SEQ ID NO: 2103 -5.5 -17.6 54.7 -12.1 0 -6.8

TTATAAAACATAGAAATAGC 3557 SEQ ID NO:2104 -5.5 -12.7 44.8 -7.2 0 -3.5

154 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular ssition oligo binding ation Duplex ture oligo oligo GGTTTATAAAACATAGAAAT

3560 SEQ ID NO: 2105 -5.5 -13.7 46.8 -6.3 -1.9 -6 GCAGAAATATTTATTTTGGT

3610 SEQ ID NO: 2106 -5.5 -18 56.6 -11.9 -0.3 -6.7 AAGCGTGTTGGTCGGAAGAG

84 SEQ ID NO: 2107 -5.4 -23.7 67.7 -17.5 -0.6 -5 GCCACTTCCACTGACTGCAT

188 SEQ ID NO: 2108 -5.4 -28.1 77.4 -22.7 0 -4.9 CATAGGGTTGGTCTGGTTTC

349 SEQ ID NO: 2109 -5.4 -24.8 75.3 -19.4 0 -1.8 CCAATGAACTGATCTGGGGC

446 SEQ ID NO: 2110 -5.4 -24.3 68.2 -18.9 0 -4.9 GCATCCTTGTTCAATAATCA

495 SEQ ID NO: 2111 -5.4 -21.7 64.4 -16.3 0 -3.4 TGGCTTCATTTCCAAGGGTA

550 SEQ ID NO: 2112 -5.4 -25 72.5 -19.1 -0.1 -3.7 GTGATGGCTTCATTTCCAAG

554 SEQ ID NO: 2113 -5.4 -23.5 69 -17.2 -0.7 -5.4 TGTACGTGATGGCTTCATTT

559 SEQ ID NO: 2114 -5.4 -23 67.8 -16.5 -0.7 -9.8 AAGCTGAACAATCGCTCACT

892 SEQ ID NO: 2115 -5.4 -22.2 63.7 -14.7 -2.1 -5.6 TCGACTGTACTTTGTGGAAG

1261 SEQ ID NO: 2116 -5.4 -21.4 64 -15.4 -0.3 -4.8 CATTTCTTCCACATCAACAA

1485 SEQ ID NO: 2117 -5.4 -20.9 61.8 -15.5 0 -1 GACATCCTTATTTCTGCACA

1884 SEQ ID NO: 2118 -5.4 -23.5 68.9 -18.1 0 -4.8 TGTGGAACTGTGCCATTTCC

2131 SEQ ID NO: 2119 -5.4 -25.7 72.9 -18.7 -1.5 -8.8 CATGAGGTGACTGTAAGGCG

2279 SEQ ID NO: 2120 -5.4 -23.4 67.4 -17.1 -0.7 -4.7 GGAAGTCTCAAATAACTTAG

2375 SEQ ID NO: 2121 -5.4 -17.2 54.7 -10.9 -0.8 -4 AGCAGGGAGACAGAAGATTT

2416 SEQ ID NO: 2122 -5.4 -21.7 65 -16.3 0 -4.1 TGCCATGAAAGAGAATCCAC

2804 SEQ ID NO: 2123 -5.4 -21.5 61.8 -15.6 -0.1 -4.6 GGAGAACCGAGTCCAAGAGC

2828 SEQ ID NO: 2124 -5.4 -25.3 70.3 -19.2 -0.5 -4.4 ATATGAAAACCACATTAAAA

3030 SEQ ID NO: 2125 -5.4 -13.7 46 -8.3 0 -3 ACTCAAGTATATACTCCCTT

3127 SEQ ID NO: 2126 -5.4 -22.3 66.2 -16.2 0 -8.7 TAAAAAATCCCTGGAGAAGT

3269 SEQ ID NO: 2127 -5.4 -18.4 55.2 -13 0 -4.8 TGGGTCTCGTGGCGTACCAG

139 SEQ ID NO: 2128 -5.3 -28.9 79.6 -21.5 -2.1 -7.4 CGCCACTTCCACTGACTGCA

189 SEQ ID NO: 2129 -5.3 -28.9 77.1 -23.6 0 -4.7 CTACCCGCCACTTCCACTGA

194 SEQ ID NO: 2130 -5.3 -30.1 78.3 -24.8 0 -2.6 GACAATTCTGCAACCTGTTT

383 SEQ ID NO: 2131 -5.3 -22.5 65.5 -17.2 0 -4.9 ATTTTGAGCAAAGATGCCAA

462 SEQ ID NO: 2132 -5.3 -20.4 60 -12.4 -2.7 -7.2 TGGCCTTCTCTGGCTTGTCA

613 SEQ ID NO: 2133 -5.3 -28.9 83.3 -21.3 -2.3 -8.5 AAGAGTTTGGCCTTCTCTGG

620 SEQ ID NO: 2134 -5.3 -25.1 73.7 -18.4 -1.2 -9.9 CACCAGTTCACTGCCGTAGG

699 SEQ ID NO: 2135 -5.3 -27.8 76.7 -20.5 -2 0

155 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

CTCTGGCCTCGTTCCACCAG 713 SEQ ID NO: 2136 -5.3 -30.6 82.6 -23.5 -1.8 -7.2

CCAGGTCCTCCATCGCCTTC 757 SEQ ID NO: 2137 -5.3 -31.9 85.5 -25.3 -1.2 -4.6

GCTGAACAATCGCTCACTAT 890 SEQ ID NO:2138 -5.3 -22.6 65 -16.3 -0.9 -3.6

AAGGATTGACTGTATTCTCT 925 SEQ ID NO:2139 -5.3 -20.5 63.3 -15.2 0 -3.3

AACGTCAGCACAGTGGCAGA 1328 SEQ ID NO: 2140 -5.3 -25.5 72.5 -19.3 -0.8 -7.4

GGCCTGCGGTCCAGTCTCCA 1429 SEQ ID NO: 2141 -5.3 -33.6 90.4 -27.4 -0.7 -7.8

ATTTCTTCCACATCAACAAG 1484 SEQ ID NO: 2142 -5.3 -20.2 60.8 -14.9 0 -2.3

AACACCTGAGCAACAGGCTC 1754 SEQ ID NO:2143 -5.3 -24.9 70.2 -16.4 -3.2 -10.5

TGCAATGAGAAATGCCTGCA 1791 SEQ ID NO:2144 -5.3 -22.8 64.3 -16.1 -1.3 -6.9

TTATTTCTGCACAGTTCCTC 1877 SEQ ID NO:2145 -5.3 -23.7 71.6 -18.4 0 -4.9

CAGGAGAAGAGATTGTGGAA 2144 SEQ ID NO: 2146 -5.3 -20 60.6 -14.7 0 -2

GAGGTGACTGTAAGGCGGTG 2276 SEQ ID NO: 2147 -5.3 -25.1 72.1 -18.9 -0.7 -5

AAAACCCACTTTTTAAACTG 2396 SEQ ID NO:2148 -5.3 -17.7 53.7 -12.4 0 -4.4

TAGAAAAGCAGGGAGACAGA 2422 SEQ ID NO:2149 -5.3 -19.8 59.6 -14.5 0 -4.1

TTGCAGCAAGTAGCAGACAT 2473 SEQ ID NO:2150 -5.3 -23.3 68.6 -16.9 -1 -8.2

CCCGCTTACTGGAAACCTTA 2718 SEQ ID NO: 2151 -5.3 -25.7 68.9 -20.4 0 -3.3

AGATAAAGTAGACAGTTATT

2973 SEQ ID NO:2152 -5.3 -16.4 53.7 -11.1 0 -3.4 AAGATAAAGTAGACAGTTAT

2974 SEQ ID NO:2153 -5.3 -15.6 51.6 -10.3 0 -3.4 GTTATTACAATGACAATTCT

3441 SEQ ID NO:2154 -5.3 -17.2 54.8 -11.9 0 -4.3

GCTCATGGGCTTGCATTGTC 10 SEQ ID NO: 2155 -5.2 -27.2 79.2 -21 -0.7 -9.3

AGTGCGGATCTTCGTGCACC 218 SEQ ID NO: 2156 -5.2 -28.1 77.6 -19.8 -3.1 -10.3

AAGCATCCTTGTTCAATAAT 497 SEQ ID NO:2157 -5.2 -19.9 60 -14.7 0 -4.1

ATGACAACTATGATTTTAAG 674 SEQ ID NO:2158 -5.2 -15.5 50.9 -9.8 -0.1 -2.7

TTACTGCAAGATCTTCAGGT 811 SEQ ID NO: 2159 -5.2 -22.2 67.2 -15.2 -0.5 -11.8

CCTTTGGGGTTGCCTGTAGT 848 SEQ ID NO: 2160 -5.2 -28.8 81.8 -22.5 -1 -4

TCCATGACACAGCATTACAC 1008 SEQ ID NO:2161 -5.2 -22.9 66.5 -17.7 0 -4.5

GATATCTCCTTGGAAAAATC 1038 SEQ ID NO: 2162 -5.2 -18.4 56.5 -13.2 0 -5.6

CCCCAACATGGCCTGCGGTC 1438 SEQ ID NO: 2163 -5.2 -32.2 81.9 -26.2 -0.6 -7.8

TTTTATCAAATTGCACGGCA 1464 SEQ ID NO: 2164 -5.2 -21 61.2 -15 -0.6 -7

GCAATGAGAAATGCCTGCAG 1790 SEQ ID NO:2165 -5.2 -22.8 64.6 -16.1 -0.6 -10.8

GCCTGTGAGAAGGGACAGTA 2620 SEQ ID NO: 2166 -5.2 -25.2 72.7 -18.7 -1.2 -5.8

156 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

Dsition oligo binding ation Duplex ture oligo oligo GTGAATGCCTGTGAGAAGGG

2626 SEQ ID NO: 2167 -5.2 -23.9 68.7 -17.9 -0.6 -3.9 GAGTTTCGTAACCCTTACGA

2660 SEQ ID NO: 2168 -5.2 -23.9 67.2 -15.6 -3.1 -11.6 TGGAGAAGAACATGAGTTTC

2673 SEQ ID NO: 2169 -5.2 -18.9 58.8 -12.8 -0.8 -5.2 GAACCGAGTCCAAGAGCATT

2825 SEQ ID NO: 2170 -5.2 -24.3 67.8 -19.1 0 -4.1 CTTAATAGCTTTAAAGAAAT

3110 SEQ ID NO: 2171 -5.2 -14.1 47.7 -8.4 0 -8.1 TATTACTGTCCATTTCAATA

3150 SEQ ID NO: 2172 -5.2 -19.2 59.5 -14 0 -3 TTCATAGAAATCAGGTAGCA

3187 SEQ ID NO: 2173 -5.2 -19.8 61 -14.6 0 -4.1 AAATGAACTTTCCAGATTTC

3239 SEQ ID NO: 2174 -5.2 -18.1 56.2 -12.9 0 -3.1 GAAGTGAATCCCAGGAAATG

3254 SEQ ID NO: 2175 -5.2 -20.5 59.7 -15.3 0 -4.9 TATTGACTTTTTGTGCAATT

3496 SEQ ID NO: 2176 -5.2 -19 59.1 -12.6 -1.1 -5.6 TAGTGCGGATCTTCGTGCAC

219 SEQ ID NO: 2177 -5.1 -25.8 73.5 -18 -2.7 -9.9 CATCATAGAAATACACCAAG

256 SEQ ID NO: 2178 -5.1 -17.5 54 -12.4 0 -2.9 TGTTGTGACATCATCATAGA

267 SEQ ID NO: 2179 -5.1 -20.5 63.4 -14.7 -0.4 -4.9 TGAGGTCATCCATGAGCAGC

1060 SEQ ID NO: 2180 -5.1 -26.1 75.8 -19.7 -1.2 -5.6 CCGCTGCGAAGCTCTGCTTC

1205 SEQ ID NO:2181 -5.1 -29.2 78.4 -21.1 -3 -12.2 TCCCACAGGCTGTTGTTTCT

1232 SEQ ID NO: 2182 -5.1 -27.9 80 -22.8 0 -5 GGCTGCTCTGAGGAACGTCA

1341 SEQ ID NO: 2183 -5.1 -26.9 75.8 -21.8 0 -6.1 CCTTCATAAAACTGACAGCC

1364 SEQ ID NO: 2184 -5.1 -22.1 63.1 -17 0 -4.1 CAGTGCACTCTGTCTGTCCG

1387 SEQ ID NO: 2185 -5.1 -27.7 79.4 -21.5 0 -10.2 GAAATACATTTGGCCCTTTC

1543 SEQ ID NO:2186 -5.1 -22.5 64.8 -17.4 0 -7.3 CTGTTCAAATGGTTTCAGAC

1950 SEQ ID NO: 2187 -5.1 -20.4 62.5 -15.3 0 -3.1 AGAGGTCATCTATCTGCGAC

2071 SEQ ID NO: 2188 -5.1 -23.8 70.8 -18.7 0 -4.2 CTCTGAGCTTTCTTCTTCAC

2112 SEQ ID NO: 2189 -5.1 -23.8 73 -18.7 0 -4.8 CAGCAGGAGAAGAGATTGTG

2147 SEQ ID NO:2190 -5.1 -21.4 64.4 -16.3 0 -4.1 TCCCTACACTTGCTGTATTC

2190 SEQ ID NO: 2191 -5.1 -25.2 73.3 -19.3 -0.6 -4 AAGTCTCAAATAACTTAGCA

2373 SEQ ID NO: 2192 -5.1 -17.9 56.1 -12.3 -0.2 -5.6 AAACCCACTTTTTAAACTGA

2395 SEQ ID NO: 2193 -5.1 -19 56.5 -13.9 0 -4.4 GCAGGGAGACAGAAGATTTA

2415 SEQ ID NO: 2194 -5.1 -21.4 64.1 -16.3 0 -3.4 ATCTGCATGGTTCTGAGTTG

2748 SEQ ID NO: 2195 -5.1 -23.5 71.2 -18.4 0 -4.9 ACTACCCGCCACTTCCACTG

195 SEQ ID NO: 2196 -5 -29.7 77.6 -24.7 0 -2.6 ATTCCCCTCTGGAAACCTTC

293 SEQ ID NO: 2197 -5 -26.7 73.2 -19.7 -2 -6.1

157 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CAGTCTTGAAGCCCTTCTGG 427 SEQ ID NO:2198 -5 -26.5 75.4 -20.8 -0.4 -6.7

CCTTGTTCAATAATCACCCA 491 SEQ ID NO:2199 -5 -23.7 66.7 -18.7 0 -3.4

TGGAGGCTTGGGCTTCCGTC 789 SEQ ID NO:2200 -5 -29.8 83 -20.6 -4.2 -10.3

TCCTTTGGGGTTGCCTGTAG 849 SEQ ID NO:2201 -5 -28 79.9 -21.9 -1 -4.3

CATCTGGGCAAGGATTGACT 934 SEQ ID NO:2202 -5 -23.8 68.7 -17.5 -1.2 -6.1

CACCATCAGCCGGACTCTTC 1290 SEQ ID NO:2203 -5 -28 77 -23 0 -6.7

TCCAGGCATGGTTAGGCAGC 1413 SEQ ID NO:2204 -5 -28.5 81.3 -22 -1.4 -9.4

CATTTGGTAACCATTTTCCA 1636 SEQ ID NO:2205 -5 -22.6 65.4 -16.9 -0.4 -5.8

AGGCTTTCTCCGTGGACAAA 1772 SEQ ID NO:2206 -5 -25.1 70.5 -19.6 -0.2 -5.6

GAAATGCCTGCAGGCTTTCT 1783 SEQ ID NO:2207 -5 -25.8 72.6 -15 -3.1 -19.8

AATGAGAAATGCCTGCAGGC 1788 SEQ ID NO:2208 -5 -23.3 65.9 -14.3 -1.3 -16.2

TAATGTCTCAACATCTGGTA 1818 SEQ ID NO:2209 -5 -20.2 62.1 -13.6 -1.6 -4.7

TTCCTCAAACGACCCTTCAA 1863 SEQ ID NO:2210 -5 -24.3 66.4 -19.3 0 -3.5

GAATCCTTCCCAAGTCTCAC 1928 SEQ ID NO:2211 -5 -25.5 72.4 -20.5 0 -2.3

GAGAAGAGATTGTGGAACTG 2141 SEQ ID NO:2212 -5 -19.2 59 -13.5 -0.5 -4

CACGAACGCTTCCTTCCCTA 2204 SEQ ID NO:2213 -5 -27.8 73.2 -22.8 0 -4.6

GAATGGACAAGTCAAACACG 2220 SEQ ID NO:2214 -5 -18.7 55.8 -13.7 0 -5.3

CACTTTTTAAACTGAGGAAG 2390 SEQ ID NO:2215 -5 -17.3 54.4 -12.3 0 -4.1

TGGTCCGCTTGTGAGATTCT 2579 SEQ ID NO:2216 -5 -26.2 75.3 -20.5 -0.4 -6.9

TCCCGCTTACTGGAAACCTT 2719 SEQ ID NO:2217 -5 -26.4 70.8 -21.4 0 -3.4

CCATGAAAGAGAATCCACGC 2802 SEQ ID NO:2218 -5 -22.3 62.3 -16.8 -0.1 -4.6

CCTGGAGAACCGAGTCCAAG 2831 SEQ ID NO:2219 -5 -25.8 69.9 -19.5 -1.2 -5.8

TCTAAGGCAGATTTTTAAAT 2885 SEQ ID NO:2220 -5 -17.3 54.9 -11.8 -0.1 -4.5

AAGTATATACTCCCTTAATA 3123 SEQ ID NO:2221 -5 -18.8 57.9 -13 0 -9.2

GGTCTCGTGGCGTACCAGAA 137 SEQ ID NO:2222 -4.9 -27.6 76.1 -21.1 -1.6 -6.8

TCATAGGGTTGGTCTGGTTT 350 SEQ ID NO:2223 -4.9 -24.8 75.3 -19.9 0 -1.9

GCTGAGCCTATGCACTCCGA 401 SEQ ID NO:2224 -4.9 -29.1 78.7 -23.4 -0.6 -5.8

CAGGTGCTGGAGGCTTGGGC 796 SEQ ID NO:2225 -4.9 -29.8 84.3 -24.2 -0.5 -4.9

AAAATTCGGTCAAACATCCG 1127 SEQ ID NO:2226 -4.9 -19.4 56.3 -13.1 -1.3 -6.1

GCGAAGCTCTGCTTCTTTCC 1200 SEQ ID NO:2227 -4.9 -27.2 77.1 -18.6 -3.7 -10.4

CGGCATCGGGGCCCCAACAT 1449 SEQ ID NO:2228 -4.9 -32 79.3 -24 -1.6 -14.4

158 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CTCAACATCTGGTACCACAA

1812 SEQ ID NO: 2229 -4.9 -22.7 65.5 -16.9 0 -9.6 ATCTATCTGCGACCTGAAAT

2064 SEQ ID NO: 2230 -4.9 -21.8 62.9 -16.9 0 -4.2 TCTGCAACATGAGGTGACTG

2286 SEQ ID NO:2231 -4.9 -22.7 66.8 -16.9 -0.7 -5.9 TTTGCAGCAAGTAGCAGACA

2474 SEQ ID NO:2232 -4.9 -23.4 69 -16.9 -1.6 -8.6 TCCACGCGTTCTGATGAGCA

2789 SEQ ID NO:2233 -4.9 -27 74.1 -21.1 -0.3 -9.8 GGCTGATCCAGGTAACTCTT

2933 SEQ ID NO: 2234 -4.9 -25.5 73.9 -19.7 -0.8 -6.5 GTCCATTTCAATAAGTACTC

3143 SEQ ID NO:2235 -4.9 -20.3 62.5 -15.4 0 -6.2 TTTGCTTATTACTGTCCATT

3156 SEQ ID NO: 2236 -4.9 -22 66.4 -17.1 0 -3.6 GCCAACACTTAAAGCAAACA

3539 SEQ ID NO: 2237 -4.9 -20.2 58.3 -15.3 0 -4.1 CCACTTCCACTGACTGCATG

187 SEQ ID NO: 2238 -4.8 -26.3 73 -21.5 0 -4.9 GTCTTGAAGCCCTTCTGGAT

425 SEQ ID NO:2239 -4.8 -26.4 75.3 -21.1 -0.2 -6.4 TGAACTGATCTGGGGCAGTC

442 SEQ ID NO: 2240 -4.8 -24.6 72 -18.2 -1.5 -5.4 ACAACTATGATTTTAAGGCC

671 SEQ ID NO:2241 -4.8 -19.9 59.7 -14.6 -0.1 -6.5 GTGGAACTGTGCCATTTCCT

2130 SEQ ID NO: 2242 -4.8 -26.6 75 -19.5 -2.3 -9.8 AGGAGAAGAGATTGTGGAAC

2143 SEQ ID NO: 2243 -4.8 -19.5 59.9 -14.7 0 -4 AAGAACCCCGAATGGACAAG

2229 SEQ ID NO: 2244 -4.8 -22.1 60.6 -16.7 -0.3 -3.3 ACAGAAGATTTAAAACCCAC

2407 SEQ ID NO: 2245 -4.8 -18.3 55.1 -13.5 0 -5 CTTTAGAGCAGCAGACAGCT

2500 SEQ ID NO: 2246 -4.8 -24.6 72.7 -18.4 -1.3 -6.3 GAACATGAGTTTCGTAACCC

2666 SEQ ID NO: 2247 -4.8 -22.4 64.3 -16.7 -0.8 -7.3 TTCTGAGTTGGATCTGCCCT

2738 SEQ ID NO: 2248 -4.8 -27.1 77.7 -21.8 -0.2 -5 GAGTCGGGGAATCAGGCCTG

2847 SEQ ID NO:2249 -4.8 -27.5 76.2 -21 -0.2 -11.6 TGGCTGATCCAGGTAACTCT

2934 SEQ ID NO:2250 -4.8 -25.4 73.3 -19.7 -0.8 -5.1 TTTTTTGGGGAAAAAGGCAA

3073 SEQ ID NO:2251 -4.8 -18.9 56.7 -12.7 -1.3 -8.5 TAATAGCTTTAAAGAAATGC

3108 SEQ ID NO: 2252 -4.8 -14.9 49.2 -10.1 0.3 -8.1 TGACAAATTATTGACTTTTT

3504 SEQ ID NO:2253 -4.8 -16.1 52.2 -10.1 -1.1 -3.6 ATGGCTTCATTTCCAAGGGT

551 SEQ ID NO: 2254 -4.7 -25.3 73 -19.9 -0.5 -4.6 ATATCAAAGTATCATCTGGG

946 SEQ ID NO: 2255 -4.7 -19.1 59.3 -14.4 0 -1.9 TACACACTCTACAACTCTCT

993 SEQ ID NO: 2256 -4.7 -21.5 65 -16.8 0 -0.2 TTGGAGGCAAAGTCCAAGAG

1178 SEQ ID NO: 2257 -4.7 -22.4 65.1 -15.7 -2 -6.6 TCAGCACAGTGGCAGACACC

1324 SEQ ID NO: 2258 -4.7 -27.1 77 -20.8 -1.6 -7.4 TCTCCGTGGACAAACACCTG

1766 SEQ ID NO:2259 -4.7 -25 68.6 -19.8 -0.1 -5.6

159 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTGCAATGAGAAATGCCTGC 1792 SEQ ID NO:2260 -4.7 -22.2 63.5 -16.1 -1.3 -6.6

CCTTATTTCTGCACAGTTCC 1879 SEQ ID NO:2261 -4.7 -25.3 73.7 -20.6 0 -4.9

GCTGTATTCAAAATTAACAA 2179 SEQ ID NO:2262 -4.7 -16 51.3 -11.3 0 -4.2

GGCGTCACAGCTGAGCATGG 2951 SEQ ID NO:2263 -4.7 -28 78.2 -21.2 -2.1 -9.2

ATTCAGGCGTCACAGCTGAG 2956 SEQ ID NO:2264 -4.7 -25.5 73.8 -19.4 -1.3 -9.1

GAAAAAGGCAAGTTAATCCC 3064 SEQ ID NO:2265 -4.7 -19.5 57.3 -14.8 0 -4

CAAGTATATACTCCCTTAAT 3124 SEQ ID NO:2266 -4.7 -19.8 59.6 -14.3 0 -9.2

TTTCAATAAGTACTCAAGTA 3138 SEQ ID NO:2267 -4.7 -16.9 54.7 -12.2 0 -6.2

TTATTACTGTCCATTTCAAT 3151 SEQ ID NO:2268 -4.7 -19.6 60.4 -14.9 0 -2.7

GTGCTTGTATATAATACATG 3404 SEQ ID NO: 2269 -4.7 -18.2 57.4 -12.2 -1.2 -6.8

AAATAGCCAACACTTAAAGC 3544 SEQ ID NO:2270 -4.7 -18.3 55.2 -13.6 0 -3.2

TTTATAAAACATAGAAATAG

3558 SEQ ID NO:2271 -4.7 -11 41.6 -6.3 0 -5.5 GTTTATAAAACATAGAAATA

3559 SEQ ID NO:2272 -4.7 -12.2 43.9 -6.3 -1.1 -6.3 GTGCGGATCTTCGTGCACCA

217 SEQ ID NO:2273 -4.6 -28.8 78.3 -21.9 -2.3 -9.1

ACTCCGACAATTCTGCAACC 388 SEQ ID NO:2274 -4.6 -24.5 67.6 -19.9 0 -4.9

ATCTGGGGCAGTCTTGAAGC 435 SEQ ID NO:2275 -4.6 -25.7 75.4 -20.5 -0.3 -4.5

ATGAACTGATCTGGGGCAGT 443 SEQ ID NO: 2276 -4.6 -24.2 70.4 -18.2 -1.3 -5.2

CCGAAAATTCGGTCAAACAT 1130 SEQ ID NO:2277 -4.6 -19.6 56.3 -12.8 -2.2 -10.5

GCTTGTCCGAAAATTCGGTC 1136 SEQ ID NO:2278 -4.6 -23.8 66.8 -16.4 -2.8 -11.7

GCGTGGTGTTTGCTTGTCCG 1147 SEQ ID NO:2279 -4.6 -28.8 79.9 -24.2 0 -4

CCAGCCGTCTTTGTCCAAAG 1599 SEQ ID NO:2280 -4.6 -26.9 73.3 -21.6 -0.5 -8.1

CTCCGTGGACAAACACCTGA 1765 SEQ ID NO:2281 -4.6 -25.2 68.4 -19.8 -0.6 -5.6

CATAATGTCTCAACATCTGG 1820 SEQ ID NO:2282 -4.6 -20 60.8 -13.8 -1.6 -5.8

TCTATCTGCGACCTGAAATA 2063 SEQ ID NO:2283 -4.6 -21.5 62.4 -16.9 0 -4.2

AGCAGGAGAAGAGATTGTGG 2146 SEQ ID NO:2284 -4.6 -21.9 65.8 -17.3 0 -4.1

AAGCAGGGAGACAGAAGATT 2417 SEQ ID NO:2285 -4.6 -20.9 62.5 -16.3 0 -4.1

TGGAGAAGTGAATCCCAGGA 3258 SEQ ID NO:2286 -4.6 -23.7 67.5 -18.3 -0.6 -4.5

AGTGTTATTACAATGACAAT 3444 SEQ ID NO:2287 -4.6 -17 54.3 -11.7 -0.5 -6.3

CTTCCACTGACTGCATGGAG 184 SEQ ID NO:2288 -4.5 -25.2 71.9 -18.7 -2 -8.4

AAGGGCTCGTCGCTGTCAAG 239 SEQ ID NO:2289 -4.5 -26.3 73.6 -20.8 -0.9 -5.1

CTCCGACAATTCTGCAACCT 387 SEQ ID NO:2290 -4.5 -25.2 68.8 -20.7 0 -4.9

160 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CTATTTTGAGCAAAGATGCC 464 SEQ ID NO:2291 -4.5 -21 62.1 -14.3 -2.2 -6.9

AAATTACTGCAAGATCTTCA 814 SEQ ID NO:2292 -4.5 -18.4 57 -13.4 -0.2 -7.7

TTGCCTGTAGTTCCACTTGT 839 SEQ ID NO:2293 -4.5 -26.5 77.2 -22 0 -3

AACCACGGGGAAGACAGTGG 1092 SEQ ID NO:2294 -4.5 -24.6 67.7 -17.9 -2.2 -7.1

CGCTGCGAAGCTCTGCTTCT 1204 SEQ ID NO:2295 -4.5 -28.1 76.9 -19.9 -3.7 -11.9

TAGGCAGCACCCGGCAGTGC 1401 SEQ ID NO:2296 -4.5 -31.6 84.4 -24.6 -2.5 -12

ATAGAGGTCATCTATCTGCG 2073 SEQ ID NO:2297 -4.5 -22.7 68.1 -16.7 -1.4 -6.8

TTATTCAGGCGTCACAGCTG 2958 SEQ ID NO:2298 -4.5 -24.7 71.9 -19.3 -0.6 -8.6

AGAAATGCTTGCCTGAGAGT 3096 SEQ ID NO:2299 -4.5 -23.1 67.2 -18.6 0 -3.9

ATGCAGAAATATTTATTTTG 3612 SEQ ID NO:2300 -4.5 -15.6 51.2 -10.5 -0.3 -7.2

CATAAGCGTGTTGGTCGGAA 87 SEQ ID NO:2301 -4.4 -23.5 66.5 -19.1 0 -3.3

AGAGCCTAAACAAGGGCCAT 327 SEQ ID NO:2302 -4.4 -24.7 68.3 -18.4 -1.9 -7.6

TGAAGCCCTTCTGGATCAGT 421 SEQ ID NO:2303 -4.4 -26.1 74.4 -20.8 -0.7 -6.7

TCCTTGTTCAATAATCACCC 492 SEQ ID NO:2304 -4.4 -23.4 67 -19 0 -3.4

GATTTTAAGGCCTGGTATTA 663 SEQ ID NO:2305 -4.4 -21.7 64.8 -16.6 0 -8.7

AACTATGATTTTAAGGCCTG 669 SEQ ID NO:2306 -4.4 -19.9 59.8 -14.8 0 -8.7

AGGTGCTGGAGGCTTGGGCT 795 SEQ ID NO:2307 -4.4 -30 85.3 -24.2 -1.3 -6.1

CTCCTTTGGGGTTGCCTGTA

850 SEQ ID NO:2308 -4.4 -28.9 81.6 -23.4 -1 -4.3 GCTCCTTTGGGGTTGCCTGT

851 SEQ ID NO:2309 -4.4 -31 86.8 -25.5 -1 -4.8 TCCGAAAATTCGGTCAAACA

1131 SEQ ID NO:2310 -4.4 -20 57.4 -12.8 -2.8 -11.7

GAAGCTCTGCTTCTTTCCTC

1198 SEQ ID NO:2311 -4.4 -25.9 76.7 -18.3 -3.2 -10.1

GTTTCTGATGATGCCGCTGC

1218 SEQ ID NO:2312 -4.4 -27 75.7 -22.1 -0.2 -5 TGTTTCTGATGATGCCGCTG

1219 SEQ ID NO:2313 -4.4 -25.2 71.3 -20.8 0 -4.7 TGTACTTTGTGGAAGATCAG

1256 SEQ ID NO:2314 -4.4 -20.2 62.5 -14.9 -0.7 -5.4

CATCAGCCGGACTCTTCCGC 1287 SEQ ID NO:2315 -4.4 -29.7 79.2 -22.4 -2.9 -9.2

CCGCAGCTCTGGCCTTTTCG 2040 SEQ ID NO:2316 -4.4 -30.7 81.3 -25.8 -0.1 -7.2

ATTGTGGAACTGTGCCATTT 2133 SEQ ID NO:2317 -4.4 -23.4 68 -18.2 -0.6 -4.4

AGAAGAGATTGTGGAACTGT 2140 SEQ ID NO:2318 -4.4 -19.8 60.8 -14.7 -0.5 -4

AGAAAAGCAGGGAGACAGAA 2421 SEQ ID NO:2319 -4.4 -19.4 58.2 -15 0 -4.1

TGGATCTGCCCTCCCGCTTA 2730 SEQ ID NO:2320 -4.4 -31.5 82.6 -26.5 -0.3 -6.3

ACATTTGCTTATTACTGTCC 3159 SEQ ID NO:2321 -4.4 -22.1 66.6 -17.7 0 -3.6

161 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TTTAAAAAATCCCTGGAGAA 3271 SEQ ID NO:2322 -4.4 -17.4 53 -13 0 -4.8

TGGTTTATAAAACATAGAAA 3561 SEQ ID NO:2323 -4.4 -13.7 46.7 -7.4 -1.9 -7.6

ATTTTGGTTTCCTTCATTGT 3598 SEQ ID NO:2324 -4.4 -22.7 69 -18.3 0 -2.5

TGCAGAAATATTTATTTTGG 3611 SEQ ID NO: 2325 -4.4 -16.8 53.7 -11.9 -0.2 -6.1

GGGTCTCGTGGCGTACCAGA 138 SEQ ID NO: 2326 -4.3 -29.5 81.2 -23.1 -2.1 -7.4

GGTTGGTCTGGTTTCCGAGA 344 SEQ ID NO: 2327 -4.3 -27.2 78.4 -22.3 -0.3 -4.1

TGCAACCTGTTTATATGAAA 375 SEQ ID NO:2328 -4.3 -18.9 57.1 -14.6 0 -4.7

AATTCTGCAACCTGTTTATA 380 SEQ ID NO:2329 -4.3 -20.4 61.3 -16.1 0 -4.7

TTGAAGCCCTTCTGGATCAG 422 SEQ ID NO:2330 -4.3 -25 71.4 -19.7 -0.9 -6.7

ACGTGATGGCTTCATTTCCA 556 SEQ ID NO:2331 -4.3 -25.2 71.6 -20.2 -0.4 -7.3

GGCCTGGTATTAACTTATTT 655 SEQ ID NO: 2332 -4.3 -22.2 65.8 -17.4 -0.2 -6.8

ATCTGGGCAAGGATTGACTG 933 SEQ ID NO: 2333 -4.3 -23.1 67.4 -17.5 -1.2 -6.1

TGTCCGAAAATTCGGTCAAA 1133 SEQ ID NO:2334 -4.3 -20.3 58.4 -13.2 -2.8 -11.7

GTTCCTCAAACGACCCTTCA 1864 SEQ ID NO:2335 -4.3 -26.2 71.5 -21.2 -0.5 -3.5

TGCCATTTCCTCTGAGCTTT 2121 SEQ ID NO:2336 -4.3 -26.8 76.7 -22 -0.2 -5.7

AGACAGAAGATTTAAAACCC 2409 SEQ ID NO:2337 -4.3 -18 54.8 -13.7 0 -5

TGTGAGAAGGGACAGTAGCA 2617 SEQ ID NO:2338 -4.3 -23 68.4 -18.7 0 -4.1

AAGAACATGAGTTTCGTAAC 2668 SEQ ID NO:2339 -4.3 -17.7 55.2 -12.5 -0.8 -7.3

CGCTTACTGGAAACCTTATG 2716 SEQ ID NO:2340 -4.3 -21.7 62.1 -17.4 0 -3.3

CAGTGAAGATAAAGTAGACA 2979 SEQ ID NO:2341 -4.3 -17.1 54.4 -12.8 0 -3.1

TGATCTTTTGATATGAAAAC 3040 SEQ ID NO:2342 -4.3 -15.2 50.2 -9.8 -1 -4.9

TCCCAACATGATCTTTTGAT 3048 SEQ ID NO:2343 -4.3 -22.1 64.3 -16.9 -0.8 -5.8

TTAATAGCTTTAAAGAAATG 3109 SEQ ID NO:2344 -4.3 -13.2 45.9 -8.4 0 -8.1

TTAAAAAATCCCTGGAGAAG 3270 SEQ ID NO:2345 -4.3 -17.3 52.9 -13 0 -4.8

TGAAAGCCATTCATAGGGTT 360 SEQ ID NO: 2346 -4.2 -22.3 65.3 -16.7 -1.3 -5.9

AGTCTTGAAGCCCTTCTGGA 426 SEQ ID NO:2347 -4.2 -26.4 75.7 -21.5 -0.4 -7.1

ACTATGTACGTGATGGCTTC 563 SEQ ID NO: 2348 -4.2 -22.9 67.9 -18.7 0 -5.2

TTCAGCTTTGTTGACTATGT

576 SEQ ID NO:2349 -4.2 -22 67.6 -17.8 0 -4.5 GTTCAGCTTTGTTGACTATG

577 SEQ ID NO:2350 -4.2 -22 67.6 -17.8 0 -4.5 CTTCAGGTGCTGGAGGCTTG

799 SEQ ID NO:2351 -4.2 -27 78.6 -21.6 -1.1 -5.8

GCCGCTGCGAAGCTCTGCTT 1206 SEQ ID NO:2352 -4.2 -30.6 80.8 -23.4 -3 -11.1

162 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCCACAGGCTGTTGTTTCTG 1231 SEQ ID NO:2353 -4.2 -27.5 78 -22.8 -0.1 -5

TCCGTGGACAAACACCTGAG 1764 SEQ ID NO:2354 -4.2 -24.3 66.9 -19.3 -0.6 -5.4

GGCCCAGGAACATAATGTCT 1830 SEQ ID NO:2355 -4.2 -25.2 70.3 -20.5 -0.2 -5.8

CAGAATCCTTCCCAAGTCTC 1930 SEQ ID NO: 2356 -4.2 -25.3 72.1 -20.6 -0.1 -2.8

CTATCTGCGACCTGAAATAG 2062 SEQ ID NO: 2357 -4.2 -21.1 61.3 -16.9 0 -4.2

CCGAATGGACAAGTCAAACA 2222 SEQ ID NO:2358 -4.2 -20.5 58.7 -16.3 0 -6.1

CTGGTCCGCTTGTGAGATTC 2580 SEQ ID NO:2359 -4.2 -26.2 75.3 -21.3 -0.4 -4.2

CTGCATGGTTCTGAGTTGGA 2746 SEQ ID NO:2360 -4.2 -24.9 73.6 -20.7 0 -5

CTAAGGCAGATTTTTAAATA 2884 SEQ ID NO:2361 -4.2 -16.6 53.1 -11.8 -0.3 -4.5

AATGTACAAATGACAGCTCA 3353 SEQ ID NO:2362 -4.2 -19 57.8 -14.3 -0.1 -7

GTCAAGTAGTGCGGATCTTC 225 SEQ ID NO:2363 -4.1 -23.9 71.7 -19.8 0 -5

ACACCTGTATTCCCCTCTGG 301 SEQ ID NO:2364 -4.1 -28.8 78.9 -24.7 0 -3.2

CTGGTTTCCGAGAGCCTAAA 337 SEQ ID NO: 2365 -4.1 -24.9 69.3 -20.3 -0.2 -4.7

TCTTGAAGCCCTTCTGGATC 424 SEQ ID NO:2366 -4.1 -25.6 73.6 -20.8 -0.4 -6.8

TCTATTTTGAGCAAAGATGC 465 SEQ ID NO:2367 -4.1 -19.4 59.7 -13.5 -1.8 -5.6

TCAATAATCACCCACTCAGG 485 SEQ ID NO:2368 -4.1 -22.8 65.4 -18.7 0 -3.2

CTGCAAGATCTTCAGGTGCT 808 SEQ ID NO: 2369 -4.1 -24.9 73.2 -19.3 -1.2 -10.3

ATTACTGCAAGATCTTCAGG 812 SEQ ID NO:2370 -4.1 -21 63.9 -15.1 -0.5 -11.8

TTGCTCCTTTGGGGTTGCCT 853 SEQ ID NO:2371 -4.1 -29.9 83.5 -24.5 -1.2 -5.7

TCACAAAAGCTGAACAATCG

898 SEQ ID NO: 2372 -4.1 -17.9 54 -13.1 -0.4 -5.3 TTCACAAAAGCTGAACAATC

899 SEQ ID NO:2373 -4.1 -17.2 53.6 -13.1 0 -5.1 CAGTCTCCAGGCATGGTTAG

1418 SEQ ID NO:2374 -4.1 -26.2 76.9 -20.6 -1.4 -9.4

TGGCCTGCGGTCCAGTCTCC 1430 SEQ ID NO:2375 -4.1 -32.9 89.2 -27.4 -1.3 -9.1

AGAAATGCCTGCAGGCTTTC 1784 SEQ ID NO: 2376 -4.1 -24.9 71 -15 -3.1 - -19.8

CTGTGCCATTTCCTCTGAGC 2124 SEQ ID NO:2377 -4.1 -27.8 79.3 -23.7 0 -5.7

CAAATAACTTAGCACATTTA 2367 SEQ ID NO:2378 -4.1 -16.5 52.5 -12.4 0 -4.1

TTGTTCTTATTTTTAAAGGG 2546 SEQ ID NO: 2379 -4.1 -17.6 56.4 -13.5 0 -4.6

AGATCTCTGGTCCGCTTGTG 2586 SEQ ID NO:2380 -4.1 -26.8 77.3 -22.7 0 -5.6

AAGTGAACTGCTGTTAATTT 3302 SEQ ID NO:2381 -4.1 -18.7 58 -14.1 -0.1 -7.1

CAGCTCATGGGCTTGCATTG 12 SEQ ID NO: 2382 -4 -26.3 75.2 -20.5 -1.6 -11

GAAGTCAACCAGCTCTGGCA 48 SEQ ID NO:2383 -4 -26.1 73.9 -20.5 -1.6 -8.6

163 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

TCATCATAGAAATACACCAA 257 SEQ ID NO: 2384 -4 -17.9 55 -13.9 0 -2.9

AGCGTGGTGTTTGCTTGTCC 1148 SEQ ID NO:2385 -4 -28 80.8 -23.3 -0.5 -4.5

GCGGTCCAGTCTCCAGGCAT 1424 SEQ ID NO:2386 -4 -31.4 86.6 -26.9 -0.1 -4.3

AACCCACTTTTTAAACTGAG 2394 SEQ ID NO: 2387 -4 -19.7 58.4 -15.7 0 -4.4

GTCGGGGAATCAGGCCTGGA 2845 SEQ ID NO: 2388 -4 -28.7 78.4 -22.7 -0.4 -12.2

CTTGTCTTCACTATAGAATC 2903 SEQ ID NO:2389 -4 -19.5 61.5 -15.5 0 -6

GGTAGCATTATAAGAACATT 3174 SEQ ID NO:2390 -4 -18.3 57.1 -14.3 0 -4.4

CTCTCACAGACCCCAAAACA 3382 SEQ ID NO:2391 -4 -24.5 67.1 -20.5 0 -2.4

GAGTGCTGCAAAAGCTCCGA 111 SEQ ID NO: 2392 -3.9 -25.4 70.1 -19.4 -2.1 -7.8

ACTTCCACTGACTGCATGGA 185 SEQ ID NO: 2393 -3.9 -25.4 72.2 -19.7 -1.8 -8

GAATAAGCAAAGCATCCTTG 506 SEQ ID NO: 2394 -3.9 -19.9 58.9 -15.1 -0.7 -4.4

ATTTCCAAGGGTATCATAAA 543 SEQ ID NO: 2395 -3.9 -19.3 58.6 -15.4 0 -3.6

AGTTCAGCTTTGTTGACTAT 578 SEQ ID NO: 2396 -3.9 -22 68.1 -18.1 0 -4.3

CTCCATCGCCTTCATGCTGG 750 SEQ ID NO: 2397 -3.9 -29 78.8 -24.5 -0.3 -4.9

CTTTGGGGTTGCCTGTAGTT 847 SEQ ID NO: 2398 -3.9 -26.9 78.5 -22.1 -0.8 -3.8

GAGCCATCGCTTCAGCGTGG 1161 SEQ ID NO: 2399 -3.9 -29.2 79.4 -21.8 -3.5 -13.1

TAGCCCTGAAATACATTTGG 1550 SEQ ID NO: 2400 -3.9 -21.6 62.4 -17.7 0 -3.9

ACAAACACCTGAGCAACAGG 1757 SEQ ID NO: 2401 -3.9 -22 62.6 -15.1 -3 -10.2

GTAGCAGGGATTTAAAAAGA 2603 SEQ ID NO:2402 -3.9 -18.1 56 -14.2 0 -5

ATCCAGGTAACTCTTTCTTG 2928 SEQ ID NO:2403 -3.9 -22.5 67.8 -17.7 -0.8 -3.5

TGAAAACCACATTAAAAATC 3027 SEQ ID NO: 2404 -3.9 -13.7 46 -9.8 0 -3

TTGCTTATTACTGTCCATTT 3155 SEQ ID NO: 2405 -3.9 -22 66.4 -18.1 0 -3.6

AACATTTGCTTATTACTGTC 3160 SEQ ID NO: 2406 -3.9 -19.4 60.5 -15.5 0 -3.6

TAGAATTTTGGCTTGTCAAA 3212 SEQ ID NO:2407 -3.9 -18.8 58.1 -12.2 -2.7 -7.9

TCTCACAGACCCCAAAACAG 3381 SEQ ID NO:2408 -3.9 -23.6 65.5 -19.7 0 -2.4

CAAGGTGACAAATTATTGAC 3509 SEQ ID NO: 2409 -3.9 -17.2 54 -12.1 -1.1 -4.7

CCATAAGCGTGTTGGTCGGA 88 SEQ ID NO: 2410 -3.8 -26.2 72.2 -22.4 0 -4.1

GACATCATCATAGAAATACA 261 SEQ ID NO:2411 -3.8 -17.2 54.3 -13.4 0 -2.9

AACCTTCGTATAATGTTGTG 280 SEQ ID NO:2412 -3.8 -20.1 60.3 -16.3 0 -3

GACACCTGTATTCCCCTCTG 302 SEQ ID NO: 2413 -3.8 -28.2 77.7 -24.4 0 -3.6

CAAATTACTGCAAGATCTTC 815 SEQ ID NO: 2414 -3.8 -18.4 57 -14.1 -0.2 -7.7

164 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GAGGTCATCCATGAGCAGCC 1059 SEQ ID NO:2415 -3.8 -28.1 79.7 -23 -1.2 -6

CACCTTGAGGTCATCCATGA 1065 SEQ ID NO:2416 -3.8 -25.7 73 -20.6 -1.2 -7.5

TGGAGGCAAAGTCCAAGAGC 1177 SEQ ID NO:2417 -3.8 -24.1 68.9 -19.1 -1.1 -5

CCGGTCCCACAGGCTGTTGT 1236 SEQ ID NO:2418 -3.8 -31.6 84.6 -27.3 -0.1 -7.1

TTTATCAAATTGCACGGCAT 1463 SEQ ID NO: 2419 -3.8 -20.9 60.9 -16.2 -0.8 -7.9

AATGTCTCAACATCTGGTAC 1817 SEQ ID NO:2420 -3.8 -20.7 63.3 -15.3 -1.6 -7

TATCTGCGACCTGAAATAGT 2061 SEQ ID NO:2421 -3.8 -21.4 62.4 -17.6 0 -4

GTGGAATAGAGGTCATCTAT

2078 SEQ ID NO:2422 -3.8 -21.1 65 -16 -1.2 -4.6 AAAGCAGGGAGACAGAAGAT

2418 SEQ ID NO:2423 -3.8 -20.1 60.1 -16.3 0 -4.1

AGCAAAGTCCTAACCCCTTG 2444 SEQ ID NO: 2424 -3.8 -25.8 70.3 -22 0 -4.1

AATGCCTGTGAGAAGGGACA 2623 SEQ ID NO:2425 -3.8 -23.6 67.3 -19 -0.6 -4.1

GGTTCTGAGTTGGATCTGCC 2740 SEQ ID NO:2426 -3.8 -26.6 78.4 -22.8 0 -5

ATCTAAGGCAGATTTTTAAA 2886 SEQ ID NO:2427 -3.8 -17.3 54.9 -12.7 -0.6 -4.9

GCTGATCCAGGTAACTCTTT 2932 SEQ ID NO:2428 -3.8 -24.4 71.6 -19.7 -0.8 -6.5

AAATTATTGACTTTTTGTGC 3500 SEQ ID NO:2429 -3.8 -17.6 55.8 -13.8 0 -3.2

TAAAGCAAACATTCAAAACC 3530 SEQ ID NO:2430 -3.8 -15.6 49.5 -11.8 0 -4.1

CAGAAATATTTATTTTGGTT 3609 SEQ ID NO:2431 -3.8 -16.3 52.9 -11.9 -0.3 -6.7

GTCTCGTGGCGTACCAGAAG 136 SEQ ID NO:2432 -3.7 -26.4 73.8 -21.1 -1.6 -5.4

CCACTACCCGCCACTTCCAC 197 SEQ ID NO:2433 -3.7 -31.5 80.2 -27.8 0 -2.6

CCCCTCTGGAAACCTTCGTA 290 SEQ ID NO:2434 -3.7 -27.9 73.8 -23.3 -0.8 -3.8

TATTCCCCTCTGGAAACCTT 294 SEQ ID NO:2435 -3.7 -26 71.1 -20.3 -2 -6.1

TGCCAATGAACTGATCTGGG 448 SEQ ID NO:2436 -3.7 -23.1 65.7 -18.6 -0.6 -4.9

TTTTGAGCAAAGATGCCAAT 461 SEQ ID NO:2437 -3.7 -20.4 60 -13.8 -2.9 -7.5

TCTTCAGGTGCTGGAGGCTT 800 SEQ ID NO:2438 -3.7 -27.4 80.7 -22.3 -1.3 -6.3

AATTACTGCAAGATCTTCAG 813 SEQ ID NO:2439 -3.7 -19.1 59.1 -14.2 0.2 -10.4

GCAAGGATTGACTGTATTCT 927 SEQ ID NO:2440 -3.7 -21.7 65.4 -16.7 -1.2 -5

GCCCTTTCACACACACCTCG 1531 SEQ ID NO:2441 -3.7 -29 77.2 -25.3 0 -2.4

CCCTTCAAATCCTCTCTTTT 1851 SEQ ID NO:2442 -3.7 -24.9 70.8 -21.2 0 -1.7

AGTGGAATAGAGGTCATCTA

2079 SEQ ID NO:2443 -3.7 -21.1 65.2 -16.5 -0.8 -3.5 ATCAGCAGGAGAAGAGATTG

2149 SEQ ID NO: 2444 -3.7 -20.6 62.8 -16.9 0 -4.1

CTACACTTGCTGTATTCAAA 2187 SEQ ID NO:2445 -3.7 -20.1 60.9 -15.6 -0.6 -4

165 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CTCCCGCTTACTGGAAACCT

2720 SEQ ID NO: 2446 -3.7 -27.2 72.2 -23.5 0 -3.5 GTGAATCCCAGGAAATGAAC

3251 SEQ ID NO: 2447 -3.7 -20.7 60 -17 0 -4.4 CTTTAAAAAATCCCTGGAGA

3272 SEQ ID NO: 2448 -3.7 -19 56.4 -15.3 0 -4.8 CAAAGACTCACAATAAAGTG

3317 SEQ ID NO: 2449 -3.7 -15.8 50.7 -11.5 -0.3 -4.4 TTCAGTCAAATGTGGCAAAG

3332 SEQ ID NO: 2450 -3.7 -19.6 59.4 -14.8 -1 -4 GAAATAGCCAACACTTAAAG

3545 SEQ ID NO:2451 -3.7 -17.1 52.8 -13.4 0 -3.2 TGTGACATCATCATAGAAAT

264 SEQ ID NO: 2452 -3.6 -17.8 55.9 -13.4 -0.6 -3.9 CACCTGTATTCCCCTCTGGA

300 SEQ ID NO: 2453 -3.6 -29.2 79.6 -24.8 -0.6 -6.3 TACGTGATGGCTTCATTTCC

557 SEQ ID NO: 2454 -3.6 -24.2 69.9 -19.5 -0.7 -9.8 GGCCTTCTCTGGCTTGTCAA

612 SEQ ID NO: 2455 -3.6 -28.2 80.7 -22.3 -2.3 -7.9 ATGATTTTAAGGCCTGGTAT

665 SEQ ID NO:2456 -3.6 -21.9 64.9 -17.6 0 -8.7 CCATCGCCTTCATGCTGGTG

748 SEQ ID NO:2457 -3.6 -28.9 78.5 -24.8 -0.2 -6.9 TCAAAGTATCATCTGGGCAA

943 SEQ ID NO: 2458 -3.6 -21.2 63.2 -17.6 0 -4 GCACCTTGAGGTCATCCATG

1066 SEQ ID NO: 2459 -3.6 -26.9 76 -22 -1.2 -7.5 GTTGTTTCTGATGATGCCGC

1221 SEQ ID NO: 2460 -3.6 -25.6 73.2 -22 0 -3.4 AGGCAGCACCCGGCAGTGCA

1400 SEQ ID NO: 2461 -3.6 -32.6 85.9 -26.1 -2.9 -12.5 GCCCTGAAATACATTTGGCC

1548 SEQ ID NO:2462 -3.6 -25.7 70 -21.4 -0.5 -7.3 TGGCCTTTTCGCCTTCATTG

2031 SEQ ID NO:2463 -3.6 -27.4 75.8 -22 -1.8 -7.2 AAACCTTGATAGTGGAATAG

2089 SEQ ID NO: 2464 -3.6 -18.1 55.8 -14.5 0 -3.3 TCTCAAATAACTTAGCACAT

2370 SEQ ID NO: 2465 -3.6 -18.3 56.7 -14.7 0 -4.1 GTTATTCAGGCGTCACAGCT

2959 SEQ ID NO: 2466 -3.6 -25.9 75.6 -21.5 -0.6 -5.1 CCAGATTTCTACATCCTAGA

3228 SEQ ID NO: 2467 -3.6 -23 67.7 -18.9 -0.2 -5.8 ACCTGTATTCCCCTCTGGAA

299 SEQ ID NO: 2468 -3.5 -27.8 76.1 -22.5 -1.8 -5.3 ATTCTGCAACCTGTTTATAT

379 SEQ ID NO:2469 -3.5 -21.1 63.4 -17.6 0 -4.9 CAACAAAAACCAGAGAGAGT

595 SEQ ID NO: 2470 -3.5 -18 54.6 -14.5 0 -2.8 TCCATCGCCTTCATGCTGGT

749 SEQ ID NO: 2471 -3.5 -29.3 80.4 -25 -0.6 -5.4 CTTCCCAGGTCCTCCATCGC

761 SEQ ID NO: 2472 -3.5 -31.9 85.5 -27.1 -1.2 -4.5 GCTTTCACAAAAGCTGAACA

902 SEQ ID NO: 2473 -3.5 -20.3 60 -13.4 -3.4 -9.1 CTGAGGAACGTCAGCACAGT

1334 SEQ ID NO: 2474 -3.5 -24.5 70.3 -20.3 -0.5 -5.2 TTCCAATGTCCCCTGTGTGT

1621 SEQ ID NO: 2475 -3.5 -28.6 79.3 -25.1 0 -2.2 GGACAAGTCAAACACGAACG

2216 SEQ ID NO: 2476 -3.5 -19.7 56.9 -16.2 0 -6.1

166 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GACTGTAAGGCGGTGTTCTG 2271 SEQ ID NO:2477 -3.5 -24.7 71.8 -20.5 -0.4 -5.2

TCTGGTCCGCTTGTGAGATT 2581 SEQ ID NO:2478 -3.5 -26.2 75.3 -22.7 0.1 -4.3

CTGGAGAAGAACATGAGTTT 2674 SEQ ID NO:2479 -3.5 -19.4 59.4 -15 -0.8 -5.2

AGGCAAGTTAATCCCAACAT 3059 SEQ ID NO: 2480 -3.5 -22.6 64.5 -18.4 -0.5 -4.5

CCTTAATAGCTTTAAAGAAA 3111 SEQ ID NO: 2481 -3.5 -16.1 51.3 -12.1 0 -8.1

TTCAATAAGTACTCAAGTAT 3137 SEQ ID NO:2482 -3.5 -16.8 54.4 -13.3 0 -6.2

GAATCCCAGGAAATGAACTT

3249 SEQ ID NO:2483 -3.5 -20.5 59.4 -17 0 -4.9 AAATTAACTTTAAAAAATCC

3279 SEQ ID NO:2484 -3.5 -11.6 42.5 -8.1 0 -4.3 CAAATTAACTTTAAAAAATC

3280 SEQ ID NO:2485 -3.5 -10.3 40.2 -6.8 0 -4.3 AGTGAACTGCTGTTAATTTC

3301 SEQ ID NO:2486 -3.5 -19.8 61.4 -15.4 -0.7 -7.7

TATAAAACATAGAAATAGCC 3556 SEQ ID NO:2487 -3.5 -14.6 48.2 -11.1 0 -3.2

AAATATTTATTTTGGTTTCC 3606 SEQ ID NO:2488 -3.5 -17.5 55.6 -14 0 -5.8

GTTGTGACATCATCATAGAA 266 SEQ ID NO:2489 -3.4 -19.8 61.3 -15.6 -0.6 -4.2

AAAGCATCCTTGTTCAATAA 498 SEQ ID NO:2490 -3.4 -19.2 58.1 -15.3 -0.2 -4.1

TACTGCAAGATCTTCAGGTG 810 SEQ ID NO: 2491 -3.4 -22.1 66.7 -16.9 -0.5 -11.8

GGTTGCCTGTAGTTCCACTT 841 SEQ ID NO:2492 -3.4 -27.7 80.2 -24.3 0 -3

TGCTTTCACAAAAGCTGAAC 903 SEQ ID NO: 2493 -3.4 -19.6 58.7 -12.1 -4.1 -9.2

GGCGAGAGGCAAGAAAGATA 963 SEQ ID NO:2494 -3.4 -21.5 62.1 -16.5 -1.5 -4

GTTGAAGCACCTTGAGGTCA 1072 SEQ ID NO:2495 -3.4 -25 72.6 -21.1 -0.2 -7.8

TGTTCAAATGGTTTCAGACC 1949 SEQ ID NO:2496 -3.4 -21.5 64.3 -17 -1 -5

GTGACTGTAAGGCGGTGTTC 2273 SEQ ID NO: 2497 -3.4 -25 73.3 -20.9 -0.4 -5.2

CCCTTGATTAGAAAAGCAGG 2430 SEQ ID NO: 2498 -3.4 -21.6 62.2 -18.2 4.6 -4.1

ATCCACGCGTTCTGATGAGC 2790 SEQ ID NO:2499 -3.4 -26.3 73 -22 0 -9.8

GCCTGGAGAACCGAGTCCAA 2832 SEQ ID NO:2500 -3.4 -27.6 73.6 -22.9 -1.2 -5.8

GAAAACCACATTAAAAATCT 3026 SEQ ID NO:2501 -3.4 -14.6 47.7 -11.2 0 -3

GCTTGTCAAACACATTTCAT 3202 SEQ ID NO: 2502 -3.4 -20.8 62.5 -16.9 -0.1 -4.1

TGAATCCCAGGAAATGAACT

3250 SEQ ID NO:2503 -3.4 -20.4 59 -17 0 -4.9 GACAAATTATTGACTTTTTG

3503 SEQ ID NO: 2504 -3.4 -16.1 52.2 -11.5 -1.1 -5

CACCACTACCCGCCACTTCC

199 SEQ ID NO: 2505 -3.3 -31.5 80.2 -28.2 0 -2.6

GTGACATCATCATAGAAATA

263 SEQ ID NO: 2506 -3.3 -17.5 55.4 -13.4 -0.6 -3.9

AACAAATTACTGCAAGATCT

817 SEQ ID NO : 2507 -3.3 -17.4 54.2 -13.6 -0.2 -6.1

167 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TATCATCTGGGCAAGGATTG 937 SEQ ID NO: 2508 -3.3 -22.2 65.8 -18 -0.8 -5.1

TGATATCTCCTTGGAAAAAT 1039 SEQ ID NO: 2509 -3.3 -18 55.2 -14.7 0 -6.4

TGAGGAACGTCAGCACAGTG 1333 SEQ ID NO:2510 -3.3 -23.6 68.3 -20.3 0 -5.3

TGTGTGTAACCAGCCGTCTT 1608 SEQ ID NO:2511 -3.3 -26.7 75.1 -22.9 -0.1 -3.3

TCAAATAACTTAGCACATTT 2368 SEQ ID NO:2512 -3.3 -17.2 54.2 -13.9 0 -4.1

AGAACCGAGTCCAAGAGCAT 2826 SEQ ID NO:2513 -3.3 -24.2 67.7 -20.9 0 -4.1

GATAAAGTAGACAGTTATTC 2972 SEQ ID NO: 2514 -3.3 -16.8 54.9 -13.5 0 -3.4

TATGAAAACCACATTAAAAA 3029 SEQ ID NO: 2515 -3.3 -13 44.7 -9.7 0 -3

ATTTCTACATCCTAGAATTT 3224 SEQ ID NO:2516 -3.3 -19.2 59.6 -14.4 -1.4 -4.3

ATGTACAAATGACAGCTCAA 3352 SEQ ID NO:2517 -3.3 -19 57.8 -15.1 -0.3 -7.4

AGTGCTGCAAAAGCTCCGAA 110 SEQ ID NO:2518 -3.2 -24.1 66.7 -18.8 -2.1 -7.8

CCACCACTACCCGCCACTTC 200 SEQ ID NO:2519 -3.2 -31.5 80.2 -28.3 0 -2.6

CACCACCACTACCCGCCACT 202 SEQ ID NO: 2520 -3.2 -31.9 79.7 -28.7 0 -2.6

CGTGATGGCTTCATTTCCAA 555 SEQ ID NO:2521 -3.2 -24.3 68.8 -20.2 -0.7 -5.4

GTCAACAAAAACCAGAGAGA 597 SEQ ID NO: 2522 -3.2 -18.4 55.6 -15.2 0 -2.7

ACACACTCTACAACTCTCTC 992 SEQ ID NO: 2523 -3.2 -22.2 67.1 -19 0 -0.2

TGGCAGACACCGGGGCGGCT 1315 SEQ ID NO:2524 -3.2 -32.3 82.9 -27.4 -1.7 -7.3

CTCTGTCTGTCCGTATCCTT 1380 SEQ ID NO: 2525 -3.2 -27.4 79.1 -24.2 0 -2.6

GGCCCTTTCACACACACCTC 1532 SEQ ID NO: 2526 -3.2 -29.4 80 -26.2 0 -5.6

GGAATAGAGGTCATCTATCT 2076 SEQ ID NO:2527 -3.2 -21.2 65.4 -16.1 -1.9 -5.1

TGCAGCAAGTAGCAGACATC 2472 SEQ ID NO:2528 -3.2 -23.6 69.9 -18.8 -1.6 -7.2

AGTCGGGGAATCAGGCCTGG 2846 SEQ ID NO: 2529 -3.2 -28.1 77.4 -22.9 -0.4 -12.2

ATTCAGTCAAATGTGGCAAA 3333 SEQ ID NO: 2530 -3.2 -19.6 59.2 -15.9 -0.2 -4

ACAATGACAATTCTTTAGTG 3435 SEQ ID NO:2531 -3.2 -17.5 55.4 -14.3 0 -3.1

AACATAGAAATAGCCAACAC 3551 SEQ ID NO:2532 -3.2 -17.7 54.1 -14.5 0 -3.2

CGACAATTCTGCAACCTGTT 384 SEQ ID NO:2533 -3.1 -23.2 65.4 -20.1 0 -4.9

CGCCTTCATGCTGGTGACTT 744 SEQ ID NO:2534 -3.1 -27.6 76.5 -24.5 0 -6.6

TGCTGGAGGCTTGGGCTTCC 792 SEQ ID NO:2535 -3.1 -30.1 84.4 -23.9 -3.1 -9.6

TTCAGGTGCTGGAGGCTTGG 798 SEQ ID NO:2536 -3.1 -27.3 79.3 -23 -1.1 -5.7

CAAAGTATCATCTGGGCAAG 942 SEQ ID NO: 2537 -3.1 -20.8 62 -17.7 0 -4

GATATCAAAGTATCATCTGG 947 SEQ ID NO:2538 -3.1 -18.5 58.1 -14.6 -0.6 -6.2

168 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

ACCTTGAGGTCATCCATGAG 1064 SEQ ID NO:2539 -3.1 -25 72.2 -20.6 -1.2 -7.3

CGTCAGCACAGTGGCAGACA 1326 SEQ ID NO:2540 -3.1 -26.9 76 -21.5 -2.3 -10.5

CCCAACATGGCCTGCGGTCC 1437 SEQ ID NO:2541 -3.1 -32.2 81.9 -28.3 -0.6 -7.8

TCCAATGTCCCCTGTGTGTA 1620 SEQ ID NO:2542 -3.1 -28.2 78.4 -25.1 0 -2.2

ATTTGGTAACCATTTTCCAA 1635 SEQ ID NO:2543 -3.1 -21.2 62.2 -16.9 -1.1 -5.8

AAACGACCCTTCAAATCCTC 1857 SEQ ID NO:2544 -3.1 -22.8 63.2 -19.7 0 -3.5

TCCTCAAACGACCCTTCAAA 1862 SEQ ID NO:2545 -3.1 -23.5 64.2 -20.4 0 -3.5

ATCCTTATTTCTGCACAGTT 1881 SEQ ID NO:2546 -3.1 -23.3 69.8 -20.2 0 -4.9

AGGTCATCTATCTGCGACCT 2069 SEQ ID NO:2547 -3.1 -26.1 74.9 -20.5 -2.5 -7.3

CCTACACTTGCTGTATTCAA 2188 SEQ ID NO:2548 -3.1 -22.8 66.8 -18.9 -0.6 -4

GGAGAAGAACATGAGTTTCG 2672 SEQ ID NO: 2549 -3.1 -19.7 59.4 -15.6 -0.9 -7.3

CGTCACAGCTGAGCATGGCT 2949 SEQ ID NO: 2550 -3.1 -27.7 77.5 -23.6 -0.7 -9.3

GGCTTGTCAAACACATTTCA 3203 SEQ ID NO: 2551 -3.1 -22 65 -18.4 -0.1 -7.2

CTAGAATTTTGGCTTGTCAA 3213 SEQ ID NO: 2552 -3.1 -20.4 62 -15.6 -1.7 -7.8

GAAGCCCTTCTGGATCAGTG 420 SEQ ID NO: 2553 -3 -26.1 74.4 -22.5 -0.3 -5.9

TGACAACTATGATTTTAAGG 673 SEQ ID NO: 2554 -3 -16.7 53.3 -13.2 -0.1 -2.7

TCAGGTGCTGGAGGCTTGGG 797 SEQ ID NO: 2555 -3 -28.4 81.6 -24.2 -1.1 -5.5

GCCTGTAGTTCCACTTGTGA 837 SEQ ID NO: 2556 -3 -27 78.2 -23.3 -0.5 -5.1

TTTGGGGTTGCCTGTAGTTC 846 SEQ ID NO: 2557 -3 -26.4 78.3 -22.3 -1 -4

CATTGCTCCTTTGGGGTTGC 855 SEQ ID NO: 2558 -3 -27.7 78.9 -23.8 -0.8 -5.7

GGTCAAACATCCGGTTCAGC 1120 SEQ ID NO:2559 -3 -25.6 72.2 -22.6 0 -6.6

TATCCTTCATAAAACTGACA 1367 SEQ ID NO:2560 -3 -18.4 56.3 -15.4 0 -2.6

CAAAGCTTCTGCTGTTTTCG 1584 SEQ ID NO:2561 -3 -22.8 66.6 -18.1 -1.7 -7

TGTCTCAACATCTGGTACCA 1815 SEQ ID NO:2562 -3 -24.1 70.6 -20 -0.3 -10

TCTGCACAGTTCCTCAAACG 1872 SEQ ID NO:2563 -3 -24 68.2 -19.6 -1.3 -6.5

CCCTCCCGCTTACTGGAAAC 2722 SEQ ID NO:2564 -3 -28.3 73.7 -25.3 0 -3.5

TCTGCATGGTTCTGAGTTGG 2747 SEQ ID NO:2565 -3 -24.7 74 -21.7 0 -5

TGGAGAACCGAGTCCAAGAG 2829 SEQ ID NO:2566 -3 -23.5 66.2 -19.2 -1.2 -5.7

AATCCCAGGAAATGAACTTT 3248 SEQ ID NO: 2567 -3 -20 58.5 -17 0 -4.9

TAGTGTTATTACAATGACAA 3445 SEQ ID NO: 2568 -3 -16.7 53.7 -13 -0.5 -6.3

ATCTTCAGGTGCTGGAGGCT 801 SEQ ID NO:2569 -2.9 -27.3 80.3 -23 -1.3 -6.3

169 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo AAAGCTGAACAATCGCTCAC

893 SEQ ID NO: 2570 -2.9 -20.6 60 -15.6 -2.1 -5.6 GGTTGAAGCACCTTGAGGTC

1073 SEQ ID NO: 2571 -2.9 -25.5 74.2 -22.1 -0.2 -7.8 GAACCACGGGGAAGACAGTG

1093 SEQ ID NO: 2572 -2.9 -24 66.6 -20.3 -0.6 -6.5 CGAAAATTCGGTCAAACATC

1129 SEQ ID NO: 2573 -2.9 -18 54 -14.4 -0.5 -7.1 TTTGGTAACCATTTTCCAAT

1634 SEQ ID NO: 2574 -2.9 -21.2 62.2 -16.9 -1.3 -5.8 ATTGCAATGAGAAATGCCTG

1793 SEQ ID NO: 2575 -2.9 -20.4 59.7 -16.1 -1.3 -8.5 ATGTCTCAACATCTGGTACC

1816 SEQ ID NO: 2576 -2.9 -23.4 69.4 -19.2 -1.1 -9.6 ATGGAGTCGGGGAATCAGGC

2850 SEQ ID NO: 2577 -2.9 -25.8 73.2 -21.9 -0.9 -4.7 ATGAAAACCACATTAAAAAT

3028 SEQ ID NO: 2578 -2.9 -13.3 45.2 -10.4 0 -3 CTTTAAAGAAATGCTTGCCT

3102 SEQ ID NO: 2579 -2.9 -20.1 59.3 -17.2 0.2 -7 TGCTTATTACTGTCCATTTC

3154 SEQ ID NO:2580 -2.9 -22.3 67.6 -19.4 0 -3.6 ATTCGAAAATACCGGAACAG

29 SEQ ID NO: 2581 -2.8 -18.5 54.4 -15.2 0 -7.9 TGCGGATCTTCGTGCACCAC

216 SEQ ID NO: 2582 -2.8 -27.8 75.6 -24.1 -0.8 -8.4 GTACGTGATGGCTTCATTTC

558 SEQ ID NO: 2583 -2.8 -23.4 69.6 -19.5 -0.7 -9.8 AGGCCTGGTATTAACTTATT

656 SEQ ID NO: 2584 -2.8 -22.1 65.7 -18.4 -0.2 -9.4 CTGGAGGCTTGGGCTTCCGT

790 SEQ ID NO: 2585 -2.8 -30.3 83.1 -23.3 -4.2 -10.3 TTGGGGTTGCCTGTAGTTCC

845 SEQ ID NO: 2586 -2.8 -28.3 81.7 -24.4 -1 -4 TCATCTGGGCAAGGATTGAC

935 SEQ ID NO: 2587 -2.8 -23.3 68.3 -19.2 -1.2 -5.5 GGAGGCAAAGTCCAAGAGCC

1176 SEQ ID NO:2588 -2.8 -26.1 72.6 -21.9 -1.3 -6.1 TCTGTCTGTCCGTATCCTTC

1379 SEQ ID NO: 2589 -2.8 -26.9 79 -24.1 0 -2.6 GGCTTTCTCCGTGGACAAAC

1771 SEQ ID NO: 2590 -2.8 -25.3 70.8 -22.5 0 -5.6 GAAAATAATTCAGGGTGCAA

1985 SEQ ID NO: 2591 -2.8 -18.1 55.3 -14.5 -0.6 -6.6 TCCGCAGCTCTGGCCTTTTC

2041 SEQ ID NO:2592 -2.8 -30.3 83.6 -26.5 -0.9 -7.2 TATGAGAAGAACCCCGAATG

2235 SEQ ID NO: 2593 -2.8 -21 59.2 -18.2 0 -2.8 CCCTCTAGTGCACTGTACTC

2519 SEQ ID NO: 2594 -2.8 -27.1 78.5 -23 -0.2 -10.6 ACAGTAGCAGGGATTTAAAA

2606 SEQ ID NO: 2595 -2.8 -19.1 58.4 -16.3 0 -5 TTAAAAATCTGTTGGCCTTT

3016 SEQ ID NO:2596 -2.8 -19.7 59.1 -16.9 0 -7.2 AAGGCAAGTTAATCCCAACA

3060 SEQ ID NO: 2597 -2.8 -21.9 62.5 -18.4 -0.5 -4.5 AACACATTTCATAGAAATCA

3194 SEQ ID NO: 2598 -2.8 -16.4 52.5 -12.5 -1 -5.9 CTCATGGGCTTGCATTGTCC

9 SEQ ID NO: 2599 -2.7 -27.4 78.3 -24.7 0 -6.3 AAGTCAACCAGCTCTGGCAT

47 SEQ ID NO: 2600 -2.7 -25.5 72.6 -21.2 -1.6 -8.6

170 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GGGTTGGTCTGGTTTCCGAG

345 SEQ ID NO:2601 -2.7 -27.8 79.7 -24.6 -0.2 -3.9 CTTGAAGCCCTTCTGGATCA

423 SEQ ID NO:2602 -2.7 -25.9 73 -22.3 -0.7 -6.7

AATAAGCAAAGCATCCTTGT 505 SEQ ID NO:2603 -2.7 -20.5 60.5 -17.3 -0.2 -4.4

TTGTCAACAAAAACCAGAGA 599 SEQ ID NO:2604 -2.7 -17.9 54.5 -15.2 0 -5.1

TTCCACTTGTGAAACAAATT 829 SEQ ID NO:2605 -2.7 -18.4 55.9 -13.8 -1.9 -5.4

AGGCAAAGTCCAAGAGCCAT 1174 SEQ ID NO: 2606 -2.7 -25 69.9 -19.9 -2.4 -6.6

CGGCAGTGCACTCTGTCTGT 1390 SEQ ID NO:2607 -2.7 -28.3 81.2 -24.1 -1.3 -10.2

GCCTGCGGTCCAGTCTCCAG 1428 SEQ ID NO:2608 -2.7 -32.4 88.2 -28.8 -0.7 -5.3

CTGAAATACATTTGGCCCTT 1545 SEQ ID NO:2609 -2.7 -22.9 64.8 -20.2 0 -7.3

CAATGAGAAATGCCTGCAGG 1789 SEQ ID NO:2610 -2.7 -22.2 63.1 -17.7 0 -11.8

TGGAATAGAGGTCATCTATC 2077 SEQ ID NO: 2611 -2.7 -20.3 63.2 -15.7 -1.9 -5.1

GCCATTTCCTCTGAGCTTTC 2120 SEQ ID NO:2612 -2.7 -27.2 78.7 -24.5 0 -5.7

GAAGAGATTGTGGAACTGTG 2139 SEQ ID NO:2613 -2.7 -19.8 60.5 -16.4 -0.5 -4

CCCTACACTTGCTGTATTCA 2189 SEQ ID NO:2614 -2.7 -25.5 72.8 -22 -0.6 -4

CAACATGAGGTGACTGTAAG 2282 SEQ ID NO:2615 -2.7 -19.8 60 -16.2 -0.7 -5.5

TAGCAGGGATTTAAAAAGAT 2602 SEQ ID NO:2616 -2.7 -16.9 53.3 -14.2 0 -5

GCCATGAAAGAGAATCCACG 2803 SEQ ID NO:2617 -2.7 -22.3 62.3 -19.1 -0.1 -4.6

AGGCGTCACAGCTGAGCATG 2952 SEQ ID NO:2618 -2.7 -26.8 75.9 -22 -2.1 -9.2

ATTAAAAATCTGTTGGCCTT 3017 SEQ ID NO:2619 -2.7 -19.6 58.7 -16.9 0 -7.2

ATGATCTTTTGATATGAAAA 3041 SEQ ID NO:2620 -2.7 -15 49.7 -11.2 -1 -4.9

AAAAAGGCAAGTTAATCCCA 3063 SEQ ID NO:2621 -2.7 -19.6 57.3 -16.9 0 -4

AAGTGAATCCCAGGAAATGA 3253 SEQ ID NO:2622 -2.7 -20.5 59.7 -17.8 0 -4.9

TGACATCATCATAGAAATAC 262 SEQ ID NO:2623 -2.6 -16.5 53 -13.4 -0.2 -3.1

GTATTCCCCTCTGGAAACCT 295 SEQ ID NO: 2624 -2.6 -27.1 73.9 -22.5 -2 -6.1

AGGGTTGGTCTGGTTTCCGA

346 SEQ ID NO:2625 -2.6 -27.8 79.7 -24.6 -0.3 -4.7 AGCTTTGTTGACTATGTACG

573 SEQ ID NO:2626 -2.6 -21.5 64.7 -18.9 0 -5.2

TGTCAACAAAAACCAGAGAG 598 SEQ ID NO:2627 -2.6 -17.8 54.4 -15.2 0 -3.2

CTCTAATAAGAGTTTGGCCT 627 SEQ ID NO:2628 -2.6 -22.1 65.6 -17.9 -1.4 -10

CATCGCCTTCATGCTGGTGA 747 SEQ ID NO:2629 -2.6 -27.5 76.3 -23.4 -1.4 -9.3

TTCCCAGGTCCTCCATCGCC 760 SEQ ID NO:2630 -2.6 -33 86.9 -29.1 -1.2 -4.5

GTTGCCTGTAGTTCCACTTG 840 SEQ ID NO:2631 -2.6 -26.5 77.2 -23.9 0 -3

171 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GCAGCCTGATATCTCCTTGG 1045 SEQ ID NO:2632 -2.6 -27.4 77.5 -24.8 0 -6.4

TTTCTGATGATGCCGCTGCG 1217 SEQ ID NO: 2633 -2.6 -26.6 72.3 -22.4 -1.6 -9

CCACAGGCTGTTGTTTCTGA 1230 SEQ ID NO: 2634 -2.6 -26.1 75.7 -22.8 -0.5 -4.9

GTCAGCACAGTGGCAGACAC 1325 SEQ ID NO: 2635 -2.6 -26.3 76.9 -21.9 -1.8 -10.3

TCAAATCCTCTCTTTTGGGC 1847 SEQ ID NO: 2636 -2.6 -24.1 70.4 -20.6 -0.7 -7.4

CTGCACAGTTCCTCAAACGA 1871 SEQ ID NO:2637 -2.6 -24.2 68 -20.2 -1.3 -6.5

CCAGAATCCTTCCCAAGTCT 1931 SEQ ID NO: 2638 -2.6 -26.9 74 -23.8 -0.1 -2.8

GAGGCTCCTTATCTGCATGG

2758 SEQ ID NO: 2639 -2.6 -26.6 76.5 -23.1 -0.7 -5.1 AGAGGCTCCTTATCTGCATG

2759 SEQ ID NO: 2640 -2.6 -25.4 74.1 -21.9 -0.7 -5.1 GATCCAGGTAACTCTTTCTT

2929 SEQ ID NO: 2641 -2.6 -23.1 69.3 -19.7 -0.6 -6.2

AAACACATTTCATAGAAATC 3195 SEQ ID NO: 2642 -2.6 -15 49.5 -11.1 -1.2 -6.1

AGCCCATAAGCGTGTTGGTC 91 SEQ ID NO: 2643 -2.5 -27.4 76.5 -24 -0.7 -4.6

CAAGGATTGACTGTATTCTC 926 SEQ ID NO: 2644 -2.5 -20.3 62.6 -17.1 -0.5 -4.2

GTCAAACATCCGGTTCAGCA 1119 SEQ ID NO: 2645 -2.5 -25.1 70.7 -21.9 -0.5 -6.6

GATCAGCCGGTCCCACAGGC 1242 SEQ ID NO: 2646 -2.5 -31.7 84.4 -27.3 -1.9 -10

CGGGGCGGCTCCTGTCACCA 1305 SEQ ID NO: 2647 -2.5 -33.4 86 -29.9 -0.7 -9.6

GTATCCTTCATAAAACTGAC 1368 SEQ ID NO: 2648 -2.5 -18.9 58 -16.4 0 -2.6

CGGTCCAGTCTCCAGGCATG 1423 SEQ ID NO: 2649 -2.5 -29.6 81.8 -26.6 -0.1 -5.1

TTTTCCAATGTCCCCTGTGT 1623 SEQ ID NO: 2650 -2.5 -27.6 76.8 -25.1 0 -1.8

CAATTGCAATGAGAAATGCC 1795 SEQ ID NO: 2651 -2.5 -19.5 57.3 -16.1 -0.6 -9.3

GCACAGTTCCTCAAACGACC 1869 SEQ ID NO: 2652 -2.5 -25.5 70.3 -22.3 -0.5 -5.1

TAGCAAAGTCCTAACCCCTT 2445 SEQ ID NO: 2653 -2.5 -25.5 69.9 -23 0 -4.1

AAGATCTCTGGTCCGCTTGT 2587 SEQ ID NO: 2654 -2.5 -26.1 74.9 -23.6 0 -6.3

GCATGGTTCTGAGTTGGATC 2744 SEQ ID NO: 2655 -2.5 -24.4 73.5 -21.9 0 -5

TTCAGGCGTCACAGCTGAGC 2955 SEQ ID NO: 2656 -2.5 -27.3 78.3 -23.4 -1.3 -9.1

AATAGCTTTAAAGAAATGCT 3107 SEQ ID NO: 2657 -2.5 -16.1 51.5 -12.2 -1.3 -7.4

CAGGTAGCATTATAAGAACA 3176 SEQ ID NO: 2658 -2.5 -18.9 58.2 -16.4 0 -4.4

ACAAATTATTGACTTTTTGT 3502 SEQ ID NO:2659 -2.5 -16.7 53.7 -13 -1.1 -5.5

GTGACAAATTATTGACTTTT 3505 SEQ ID NO: 2660 -2.5 -17.2 54.7 -13.5 -1.1 -3.9

GACTTCCACCCCACACCTCT 729 SEQ ID NO: 2661 -2.4 -31.1 81.8 -28.7 0 -1.5

TGGGGTTGCCTGTAGTTCCA 844 SEQ ID NO: 2662 -2.4 -28.9 82.3 -25.4 -1 -4.3

172 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GGCAAGGATTGACTGTATTC 928 SEQ ID NO:2663 -2.4 -22 66 -18.3 -1.2 -5

ATCATCTGGGCAAGGATTGA 936 SEQ ID NO:2664 -2.4 -23.1 67.7 -19.4 -1.2 -5.5

ATCAGCCGGTCCCACAGGCT 1241 SEQ ID NO:2665 -2.4 -32 85 -26.1 -3.5 -9.2

CACCCGGCAGTGCACTCTGT 1394 SEQ ID NO:2666 -2.4 -30.7 82.6 -27.1 -0.7 -10.2

TGCGGTCCAGTCTCCAGGCA 1425 SEQ ID NO:2667 -2.4 -31.4 86.4 -28.5 -0.2 -4.7

TGAAATACATTTGGCCCTTT 1544 SEQ ID NO:2668 -2.4 -22.1 63.3 -19.7 0 -7.3

CGTCTTTGTCCAAAGCTTCT 1594 SEQ ID NO:2669 -2.4 -24.5 70.6 -21.2 -0.7 -8.4

TTTCCAATGTCCCCTGTGTG 1622 SEQ ID NO:2670 -2.4 -27.5 76.3 -25.1 0 -2.2

GTTCAAATGGTTTCAGACCA 1948 SEQ ID NO:2671 -2.4 -22.2 65.6 -17.5 -2.3 -6.2

CGCAGCTCTGGCCTTTTCGC 2039 SEQ ID NO:2672 -2.4 -30.5 82.2 -27.1 -0.9 -7.2

GAGGTCATCTATCTGCGACC 2070 SEQ ID NO:2673 -2.4 -25.8 74.2 -21.7 -1.7 -6

AAGTCAAACACGAACGCTTC

2212 SEQ ID NO:2674 -2.4 -20.2 58.7 -17.8 0 -4.6 CAAGTCAAACACGAACGCTT

2213 SEQ ID NO:2675 -2.4 -20.5 58.6 -18.1 0 -4.6 TTCTGTGAATGCCTGTGAGA

2630 SEQ ID NO:2676 -2.4 -23.6 69.3 -21.2 0 -3

TTCGTAACCCTTACGAATCA 2656 SEQ ID NO:2677 -2.4 -22.4 63 -15.7 -4.3 -10.9

CTGATCCAGGTAACTCTTTC 2931 SEQ ID NO:2678 -2.4 -23 68.8 -19.7 -0.8 -6.5

AATTCAGTCAAATGTGGCAA 3334 SEQ ID NO:2679 -2.4 -19.6 59.2 -16.1 -1 -4

TTCGAAAATACCGGAACAGC 28 SEQ ID NO:2680 -2.3 -20.3 57.9 -18 0 -7.1

ATGAAAGCCATTCATAGGGT 361 SEQ ID NO:2681 -2.3 -22.2 64.9 -17.8 -2.1 -7.6

TTCAATAATCACCCACTCAG 486 SEQ ID NO:2682 -2.3 -21.7 63.2 -19.4 0 -1.6

CTTGTTCAATAATCACCCAC 490 SEQ ID NO:2683 -2.3 -21.9 63.7 -19.6 0 -3.4

TCAGCTTTGTTGACTATGTA 575 SEQ ID NO:2684 -2.3 -21.6 66.6 -19.3 0 -4.5

TGCCTGTAGTTCCACTTGTG 838 SEQ ID NO:2685 -2.3 -26.4 76.6 -23.6 -0.1 -4.7

CACAAAAGCTGAACAATCGC 897 SEQ ID NO:2686 -2.3 -19.3 56.4 -16 -0.9 -5.3

AGCACCTTGAGGTCATCCAT 1067 SEQ ID NO:2687 -2.3 -26.9 76.5 -23.3 -1.2 -7.5

ACCGGGGCGGCTCCTGTCAC 1307 SEQ ID NO:2688 -2.3 -32.9 85.7 -28.9 -1.7 -9.6

GGCAGACACCGGGGCGGCTC 1314 SEQ ID NO:2689 -2.3 -32.7 84.8 -28.7 -1.7 -7.3

CTCAAATAACTTAGCACATT 2369 SEQ ID NO:2690 -2.3 -18 55.8 -15.7 0 -4.1

CTTTAAATGTACAAATGACA 3358 SEQ ID NO:2691 -2.3 -15.3 49.8 -13 0 -6.8

AAGGTGACAAATTATTGACT 3508 SEQ ID NO:2692 -2.3 -17.4 54.6 -13.9 -1.1 -4.8

ACTTAAAGCAAACATTCAAA 3533 SEQ ID NO:2693 -2.3 -15.3 49.5 -13 0 -4.1

173 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TGCACCACCACTACCCGCCA 204 SEQ ID NO:2694 -2.2 -32.6 81.1 -30.4 0 -4.7

CTGTCAAGTAGTGCGGATCT 227 SEQ ID NO:2695 -2.2 -24.3 71.4 -22.1 0 -5.4

GATCACCATCGAATAAGCAA 516 SEQ ID NO:2696 -2.2 -20.5 59.4 -17.8 -0.1 -5.2

GCAAGATCTTCAGGTGCTGG 806 SEQ ID NO: 2697 -2.2 -25.2 73.8 -22.2 -0.5 -8.7

CTTTCACAAAAGCTGAACAA 901 SEQ ID NO: 2698 -2.2 -17.8 54.5 -14.8 -0.6 -5.1

GGCAAGAAAGATATCAAAGT 956 SEQ ID NO:2699 -2.2 -17.4 54.2 -15.2 0 -6.9

CATCCATGAGCAGCCTGATA 1054 SEQ ID NO:2700 -2.2 -25.9 72.7 -23.7 0 -4.5

GCCGGTCCCACAGGCTGTTG 1237 SEQ ID NO:2701 -2.2 -32.2 85.4 -27.3 -2.7 -10

CTGCGGTCCAGTCTCCAGGC 1426 SEQ ID NO: 2702 -2.2 -31.6 87.4 -28.9 -0.2 -4.4

AGCCCTGAAATACATTTGGC 1549 SEQ ID NO: 2703 -2.2 -23.7 66.8 -20.5 -0.9 -7.3

AATTGCAATGAGAAATGCCT 1794 SEQ ID NO: 2704 -2.2 -19.7 57.9 -16.1 -1.3 -9.3

GATTGTGGAACTGTGCCATT 2134 SEQ ID NO:2705 -2.2 -23.9 68.9 -21 -0.5 -5.2

GAAAAGCAGGGAGACAGAAG 2420 SEQ ID NO:2706 -2.2 -19.4 58.2 -17.2 0 -3.3

TGTTCTTATTTTTAAAGGGA 2545 SEQ ID NO:2707 -2.2 -18.1 57.4 -15.9 0 -4.6

CAGTAGCAGGGATTTAAAAA 2605 SEQ ID NO: 2708 -2.2 -18.2 56 -16 0 -5

ATAGCTTTAAAGAAATGCTT 3106 SEQ ID NO: 2709 -2.2 -16.9 53.5 -13.1 -1.5 -8.1

TCAAGTATATACTCCCTTAA 3125 SEQ ID NO:2710 -2.2 -20.2 61 -17.2 0 -9.2

TCAGGTAGCATTATAAGAAC 3177 SEQ ID NO:2711 -2.2 -18.6 58.3 -16.4 0 -4.4

TATAATACATGTACTCTCAC 3395 SEQ ID NO:2712 -2.2 -17.9 57 -15.2 0 -7.7

TGTCAAGTAGTGCGGATCTT 226 SEQ ID NO: 2713 -2.1 -23.5 69.8 -21.4 0 -5.4

AAACCTTCGTATAATGTTGT 281 SEQ ID NO: 2714 -2.1 -19.4 58.5 -17.3 0 -3.1

ATAAGCAAAGCATCCTTGTT 504 SEQ ID NO: 2715 -2.1 -21.3 62.8 -18.3 -0.7 -4.4

ACTATGATTTTAAGGCCTGG 668 SEQ ID NO:2716 -2.1 -21.8 64.3 -19 0 -8.7

GTTCCACTTGTGAAACAAAT 830 SEQ ID NO: 2717 -2.1 -19.5 58.4 -15.5 -1.9 -6.6

GCAAGAAAGATATCAAAGTA 955 SEQ ID NO: 2718 -2.1 -15.9 51.3 -13.8 0 -6.9

ATCCTTCATAAAACTGACAG 1366 SEQ ID NO:2719 -2.1 -18.7 57 -16.6 0 -4

GACAAACACCTGAGCAACAG 1758 SEQ ID NO:2720 -2.1 -21.4 61.4 -18.4 -0.8 -5.8

TGAATGCCTGTGAGAAGGGA 2625 SEQ ID NO:2721 -2.1 -23.3 66.8 -20.4 -0.6 -3.9

GACTGGAGAAGAACATGAGT 2676 SEQ ID NO: 2722 -2.1 -20 60.5 -17.9 0 -5.2

AATCTGTTGGCCTTTACACA 3011 SEQ ID NO: 2723 -2.1 -23.5 68.3 -21.4 0 -7.2

AGTGAATCCCAGGAAATGAA 3252 SEQ ID NO:2724 -2.1 -20.5 59.7 -18.4 0 -4.9

174 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TCACAATAAAGTGAACTGCT 3310 SEQ ID NO:2725 -2.1 -18.5 56.6 -15.1 -1.2 -6

TGTACAAATGACAGCTCAAT 3351 SEQ ID NO:2726 -2.1 -19 57.8 -16.3 -0.3 -6.5

GCTTTAAATGTACAAATGAC 3359 SEQ ID NO:2727 -2.1 -16.4 52.3 -14.3 0 -6.8

TGCTTGTATATAATACATGT 3403 SEQ ID NO:2728 -2.1 -18.2 57.4 -14.5 -1.5 -6.8

AGGTGACAAATTATTGACTT 3507 SEQ ID NO:2729 -2.1 -18.2 56.7 -14.9 -1.1 -4.5

GCGGATCTTCGTGCACCACC 215 SEQ ID NO:2730 -2 -29.8 79.1 -27.1 -0.4 -8.4

TGATGGCTTCATTTCCAAGG 553 SEQ ID NO:2731 -2 -23.5 68.3 -20.6 -0.7 -4.8

GACTATGTACGTGATGGCTT 564 SEQ ID NO:2732 -2 -23.1 67.6 -21.1 0 -5.2

CACCCTCTAATAAGAGTTTG 631 SEQ ID NO:2733 -2 -21.1 62.5 -17.2 -1.9 -5.2

CAAGATCTTCAGGTGCTGGA 805 SEQ ID NO:2734 -2 -24 70.8 -21.2 -0.4 -8.7

GTAGTTCCACTTGTGAAACA 833 SEQ ID NO:2735 -2 -21.8 65.1 -18.9 -0.8 -5.7

CCTGTAGTTCCACTTGTGAA 836 SEQ ID NO:2736 -2 -24.5 71.2 -21.8 -0.5 -5.1

TGCCGCTGCGAAGCTCTGCT 1207 SEQ ID NO:2737 -2 -30.5 80.3 -25.5 -3 -10.6

GTCCCACAGGCTGTTGTTTC 1233 SEQ ID NO:2738 -2 -28.2 81.8 -26.2 0 -4.8

GAACGTCAGCACAGTGGCAG 1329 SEQ ID NO:2739 -2 -25.5 72.5 -22.6 -0.8 -7.4

AAGCTTCTGCTGTTTTCGCT 1582 SEQ ID NO: 2740 -2 -25.5 74.1 -21.8 -1.7 -7.6

ACCTGAAATAGTTCCGCAGC 2053 SEQ ID NO:2741 -2 -24.8 69.1 -22.1 -0.5 -5.6

AAGATTTAAAACCCACTTTT 2403 SEQ ID NO:2742 -2 -18 54.8 -16 0 -5

GCAGCAAGTAGCAGACATCT 2471 SEQ ID NO:2743 -2 -24.5 72.1 -20.9 -1.6 -5.8

TGCATGGTTCTGAGTTGGAT 2745 SEQ ID NO:2744 -2 -24 71.5 -22 0 -5

ATGGCTGATCCAGGTAACTC 2935 SEQ ID NO:2745 -2 -24.5 71.3 -20.8 -1.7 -6.5

CCCAACATGATCTTTTGATA 3047 SEQ ID NO:2746 -2 -21.4 62.4 -18.3 -1 -5.7

CTGTCCATTTCAATAAGTAC 3145 SEQ ID NO:2747 -2 -19.9 61 -17.9 0 -4

ACTCACAATAAAGTGAACTG 3312 SEQ ID NO:2748 -2 -16.9 53.3 -13.4 -1.4 -5.9

ATAATACATGTACTCTCACA 3394 SEQ ID NO:2749 -2 -18.9 58.9 -16.4 0 -8.2

TTGACTTTTTGTGCAATTAA 3494 SEQ ID NO: 2750 -2 -18.3 57.1 -16.3 0 -5.6

CCAACACTTAAAGCAAACAT 3538 SEQ ID NO:2751 -2 -18.4 54.8 -16.4 0 -4.1

ACAGCTCATGGGCTTGCATT 13 SEQ ID NO: 2752 -1.9 -26.5 76 -22.8 -1.6 -11

AAGCCCATAAGCGTGTTGGT 92 SEQ ID NO:2753 -1.9 -26.3 72.5 -23.5 -0.7 -4.6

CACTTCCACTGACTGCATGG 186 SEQ ID NO:2754 -1.9 -25.5 72 -23.1 -0.2 -5.4

TGCTGAGCCTATGCACTCCG 402 SEQ ID NO: 2755 -1.9 -28.5 77.3 -25.1 -1.4 -5.8

175 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TGACACAGCATTACACACTC 1004 SEQ ID NO:2756 -1.9 -22 65.3 -20.1 0 -4.1

CTCTGAGGAACGTCAGCACA 1336 SEQ ID NO:2757 -1.9 -24.6 70.3 -21.5 -1.1 -5.7

GTTAGGCAGCACCCGGCAGT 1403 SEQ ID NO:2758 -1.9 -31.1 84.2 -27.6 -1.5 -6.1

CCAGGCATGGTTAGGCAGCA 1412 SEQ ID NO:2759 -1.9 -28.8 80.4 -26 -0.8 -8.2

AAAGCTTCTGCTGTTTTCGC 1583 SEQ ID NO:2760 -1.9 -23.9 69.7 -20.3 -1.7 -7.4

CCATTTGGTAACCATTTTCC 1637 SEQ ID NO:2761 -1.9 -23.9 67.9 -21.5 -0.1 -5.5

CATCCTTATTTCTGCACAGT 1882 SEQ ID NO:2762 -1.9 -23.9 70.6 -22 0 -4.9

CCTGAAATAGTTCCGCAGCT 2052 SEQ ID NO:2763 -1.9 -25.5 70.4 -22.9 -0.5 -5.6

AGAAGGGTTCTGTGAATGCC 2637 SEQ ID NO:2764 -1.9 -23.8 69.4 -21.2 -0.5 -4.7

ACTGGAGAAGAACATGAGTT 2675 SEQ ID NO:2765 -1.9 -19.5 59.6 -16.8 -0.6 -5.2

CTTATGCTCCAACAGAAACC 2702 SEQ ID NO:2766 -1.9 -22.1 63.1 -20.2 0 -2.9

CCACGCGTTCTGATGAGCAC 2788 SEQ ID NO:2767 -1.9 -26.8 73.1 -23.9 -0.4 -9.8

CAGTTATTCAGGCGTCACAG 2961 SEQ ID NO:2768 -1.9 -23.9 70.5 -22 0 -5.1

CATTAAAAATCTGTTGGCCT 3018 SEQ ID NO:2769 -1.9 -20.2 59.6 -18.3 0 -7.2

TTAAAGAAATGCTTGCCTGA 3100 SEQ ID NO:2770 -1.9 -19.7 58.3 -17.2 -0.3 -3.9

TGAGTGCTGCAAAAGCTCCG 112 SEQ ID NO:2771 -1.8 -24.8 68.7 -21.5 -1.4 -8.2

TTGTTCAATAATCACCCACT 489 SEQ ID NO:2772 -1.8 -21.9 63.7 -20.1 0 -3.1

ATTGCTCCTTTGGGGTTGCC 854 SEQ ID NO: 2773 -1.8 -29 81.4 -25.9 -1.2 -5.7

CAGCACAGTGGCAGACACCG 1323 SEQ ID NO:2774 -1.8 -27.5 75.1 -24.1 -1.6 -7.4

GAATAGAGGTCATCTATCTG 2075 SEQ ID NO:2775 -1.8 -20 62.5 -16.3 -1.9 -5.1

AGATTTAAAACCCACTTTTT 2402 SEQ ID NO:2776 -1.8 -18.8 56.8 -16.5 -0.2 -5

GAGACAGAAGATTTAAAACC 2410 SEQ ID NO:2777 -1.8 -16.6 52.4 -14.8 0 -5

TCGGGGAATCAGGCCTGGAG 2844 SEQ ID NO:2778 -1.8 -27.5 75.4 -23.7 -0.4 -12.2

ATCTGTTGGCCTTTACACAG 3010 SEQ ID NO:2779 -1.8 -24.2 71 -21.5 -0.7 -7.2

TAAAAATCTGTTGGCCTTTA 3015 SEQ ID NO:2780 -1.8 -19.3 58.2 -17.5 0 -7.2

AAGAAATGCTTGCCTGAGAG 3097 SEQ ID NO:2781 -1.8 -21.2 62 -19.4 0 -3.9

ATTGACTTTTTGTGCAATTA 3495 SEQ ID NO:2782 -1.8 -19 59.1 -16.3 -0.8 -5.6

TCGAAAATACCGGAACAGCT 27 SEQ ID NO: 2783 -1.7 -21.1 59.2 -19.4 0 -7.1

TCTTCGTGCACCACCACTAC 210 SEQ ID NO:2784 -1.7 -27.1 75 -24.9 -0.1 -7.9

TTCTGCAACCTGTTTATATG 378 SEQ ID NO:2785 -1.7 -21.1 63.3 -19.4 0 -4.9

TGCAAGATCTTCAGGTGCTG 807 SEQ ID NO:2786 -1.7 -24 71 -21 -1.2 -9.2

176 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GAAAGATATCAAAGTATCAT 951 SEQ ID NO: 2787 -1.7 -15.2 50.2 -12 -1.4 -6.9

GAGGCAAGAAAGATATCAAA 958 SEQ ID NO:2788 -1.7 -16.8 52.7 -15.1 0 -6.9

CACGGGGAAGACAGTGGGTT 1089 SEQ ID NO:2789 -1.7 -25.6 71.8 -23.9 0 -4.6

GCACCCGGCAGTGCACTCTG 1395 SEQ ID NO:2790 -1.7 -31.3 83.4 -26.8 -2.8 -12.6

CATGGCCTGCGGTCCAGTCT 1432 SEQ ID NO: 2791 -1.7 -31.2 84.7 -27.8 -1.7 -9.9

CCCTGAAATACATTTGGCCC 1547 SEQ ID NO: 2792 -1.7 -25.9 69.4 -24.2 0 -7.3

TGCACAGTTCCTCAAACGAC 1870 SEQ ID NO: 2793 -1.7 -23.5 66.7 -20.4 -1.3 -6.4

GAAGATTTAAAACCCACTTT 2404 SEQ ID NO:2794 -1.7 -18.5 55.6 -16.8 0 -4.5

AAAAGGCAAGTTAATCCCAA 3062 SEQ ID NO:2795 -1.7 -19.6 57.3 -17.9 0 -3.3

GGAAATGAACTTTCCAGATT 3241 SEQ ID NO: 2796 -1.7 -19.4 58.3 -14.7 -3 -7.5

ACATATATGAAGTTAGGCTA

3470 SEQ ID NO: 2797 -1.7 -18.8 58.8 -16.6 0 -8.3 TACATATATGAAGTTAGGCT

3471 SEQ ID NO:2798 -1.7 -18.8 58.8 -16.6 0 -8.2 ATACATATATGAAGTTAGGC

3472 SEQ ID NO:2799 -1.7 -17.9 56.8 -15.7 0 -8.2 ATAGCCAACACTTAAAGCAA

3542 SEQ ID NO: 2800 -1.7 -19.7 58.1 -17.3 -0.4 -4.1

GTGCTGCAAAAGCTCCGAAG 109 SEQ ID NO: 2801 -1.6 -24.1 66.7 -20.4 -2.1 -7.8

GTGCACCACCACTACCCGCC 205 SEQ ID NO: 2802 -1.6 -33.1 83.4 -31 -0.1 -7.8

GTGCTGAGCCTATGCACTCC 403 SEQ ID NO: 2803 -1.6 -28.9 81.2 -24.8 -2.5 -7.8

ATGCCAATGAACTGATCTGG 449 SEQ ID NO:2804 -1.6 -21.9 63.3 -19.8 -0.2 -4.9

TGCTCCTTTGGGGTTGCCTG 852 SEQ ID NO: 2805 -1.6 -29.8 82.8 -26.9 -1.2 -5.7

CCGGGGCGGCTCCTGTCACC 1306 SEQ ID NO: 2806 -1.6 -34.7 88.2 -32 -0.8 -9.6

GCTCTGAGGAACGTCAGCAC 1337 SEQ ID NO: 2807 -1.6 -25.7 73.5 -22.9 -1.1 -6.5

ACCCGGCAGTGCACTCTGTC 1393 SEQ ID NO:2808 -1.6 -30.4 83.4 -27.6 -0.5 -10.2

AATAGAGGTCATCTATCTGC 2074 SEQ ID NO:2809 -1.6 -21.2 65.5 -17.7 -1.9 -6.2

GGTCTGCAACATGAGGTGAC 2288 SEQ ID NO:2810 -1.6 -24.2 70.9 -22 -0.3 -6

GGTTCTGTGAATGCCTGTGA 2632 SEQ ID NO: 2811 -1.6 -25.4 73.7 -23.8 0 -5.1

TTACGAATCAGAAGGGTTCT 2646 SEQ ID NO:2812 -1.6 -20.7 62 -18.2 -0.8 -6

TAAAGTAGACAGTTATTCAG 2970 SEQ ID NO:2813 -1.6 -16.9 55 -15.3 0 -2.9

GTTAATCCCAACATGATCTT 3053 SEQ ID NO:2814 -1.6 -21.6 63.3 -20 0 -5.2

TCCCAGGAAATGAACTTTCC 3246 SEQ ID NO: 2815 -1.6 -23.1 65.1 -19.6 -1.9 -6.1

AAAGATATCAAAGTATCATC 950 SEQ ID NO:2816 -1.5 -15 50.1 -12 -1.4 -6.9

AGGTCATCCATGAGCAGCCT 1058 SEQ ID NO:2817 -1.5 -28.4 80.3 -25.6 -1.2 -6

177 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CAGTGGCAGACACCGGGGCG

1318 SEQ ID NO: 2818 -1.5 -30.3 79.2 -27.2 -1.6 -7.3 AGTTCCTCAAACGACCCTTC

1865 SEQ ID NO: 2819 -1.5 -25.5 70.7 -22.6 -1.3 -3.8 AGCTCTGGCCTTTTCGCCTT

2036 SEQ ID NO: 2820 -1.5 -30.2 83.1 -26.9 -1.8 -7.3 TGGTCTGCAACATGAGGTGA

2289 SEQ ID NO: 2821 -1.5 -24 70.2 -21.9 -0.3 -6 TTTCGTAACCCTTACGAATC

2657 SEQ ID NO: 2822 -1.5 -21.8 62.2 -15.7 -4.6 -11.4 AGTTTCGTAACCCTTACGAA

2659 SEQ ID NO: 2823 -1.5 -22.6 63.9 -16.7 -4.4 -12.2 ACAGTTATTCAGGCGTCACA

2962 SEQ ID NO: 2824 -1.5 -24.1 70.8 -22.6 0 -5.1 CATGATCTTTTGATATGAAA

3042 SEQ ID NO: 2825 -1.5 -16.4 52.7 -13.8 -1 -5.6 TGTCCATTTCAATAAGTACT

3144 SEQ ID NO: 2826 -1.5 -19.9 61 -18.4 0 -6 TTTAAATGTACAAATGACAG

3357 SEQ ID NO:2827 -1.5 -14.4 48.2 -12.9 0 -6.8 AACACTTAAAGCAAACATTC

3536 SEQ ID NO: 2828 -1.5 -16.2 51.5 -14.7 0 -4.1 ATCACCATCGAATAAGCAAA

515 SEQ ID NO: 2829 -1.4 -19.2 56.5 -17.8 0 -5.2 GACAACTATGATTTTAAGGC

672 SEQ ID NO:2830 -1.4 -18.5 57.3 -16.6 -0.1 -2.9 TGACTTCCACCCCACACCTC

730 SEQ ID NO: 2831 -1.4 -30.2 79.8 -28.8 0 -2 TCATCCATGAGCAGCCTGAT

1055 SEQ ID NO:2832 -1.4 -26.6 74.9 -25.2 0 -4.5 TCCTTCCCTACACTTGCTGT

2194 SEQ ID NO: 2833 -1.4 -28.4 79.5 -27 0 -3.6 GAAGGGTTCTGTGAATGCCT

2636 SEQ ID NO: 2834 -1.4 -24.7 71.1 -22.6 -0.4 -4.7 GCTTACTGGAAACCTTATGC

2715 SEQ ID NO:2835 -1.4 -22.7 65.6 -21.3 0 -3.3 TTTAAAGAAATGCTTGCCTG

3101 SEQ ID NO: 2836 -1.4 -19.2 57.4 -17.2 -0.3 -4.7 AGGTAGCATTATAAGAACAT

3175 SEQ ID NO:2837 -1.4 -18.2 56.9 -16.8 0 -4.4 CTCAATTCAGTCAAATGTGG

3337 SEQ ID NO: 2838 -1.4 -19.8 60.5 -18.4 0 -2.5 CAACACTTAAAGCAAACATT

3537 SEQ ID NO: 2839 -1.4 -16.5 51.6 -15.1 0 -4.1 AATAGCCAACACTTAAAGCA

3543 SEQ ID NO: 2840 -1.4 -19.7 58.1 -17.6 -0.4 -4.1 ACTTCCACCCCACACCTCTG

728 SEQ ID NO: 2841 -1.3 -30.5 80.3 -29.2 0 -1.8 ACAAATTACTGCAAGATCTT

816 SEQ ID NO: 2842 -1.3 -18.2 56.3 -16.4 -0.2 -7.5 CGGTCAAACATCCGGTTCAG

1121 SEQ ID NO: 2843 -1.3 -24.6 68.2 -22.1 -1.1 -6.6 GTCCGAAAATTCGGTCAAAC

1132 SEQ ID NO: 2844 -1.3 -20.5 58.9 -16.4 -2.8 -11.7 AGAGCCATCGCTTCAGCGTG

1162 SEQ ID NO: 2845 -1.3 -28 77.2 -24.8 -1.9 -9.9 TTGGTAACCATTTTCCAATG

1633 SEQ ID NO: 2846 -1.3 -21.1 61.8 -18.7 -1 -5.8 CCTCAAACGACCCTTCAAAT

1861 SEQ ID NO: 2847 -1.3 -23.1 63 -21.8 0 -3.5 TCCTTATTTCTGCACAGTTC

1880 SEQ ID NO: 2848 -1.3 -23.7 71.6 -22.4 0 -4.9

178 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo CAGCTCTGGCCTTTTCGCCT

2037 SEQ ID NO: 2849 -1.3 -30.8 83.7 -27.7 -1.8 -7.4 GGAACTGTGCCATTTCCTCT

2128 SEQ ID NO:2850 -1.3 -26.7 75.4 -23.8 -1.6 -9 CCTGTGAGAAGGGACAGTAG

2619 SEQ ID NO: 2851 -1.3 -23.4 68.7 -20.8 -1.2 -5.8 AGTTATTCAGGCGTCACAGC

2960 SEQ ID NO: 2852 -1.3 -25 73.8 -23.7 0 -5.1 CCACATTAAAAATCTGTTGG

3021 SEQ ID NO: 2853 -1.3 -18.4 55.7 -17.1 0 -2.8 ATCAGGTAGCATTATAAGAA

3178 SEQ ID NO: 2854 -1.3 -18.4 57.7 -17.1 0 -4.4 GTACAAATGACAGCTCAATT

3350 SEQ ID NO: 2855 -1.3 -19.1 58.2 -17.2 -0.3 -5.2 CTTAAAGCAAACATTCAAAA

3532 SEQ ID NO: 2856 -1.3 -14.4 47.6 -13.1 0 -4.1 CATCGAATAAGCAAAGCATC

510 SEQ ID NO: 2857 -1.2 -18.8 56.3 -16.7 -0.7 -5.9 CTGGCTTGTCAACAAAAACC

604 SEQ ID NO: 2858 -1.2 -20.8 60.1 -18.7 -0.8 -5.2 CTGTAGTTCCACTTGTGAAA

835 SEQ ID NO: 2859 -1.2 -21.8 65.1 -19.9 -0.5 -5.1 AGGCATGGTTAGGCAGCACC

1410 SEQ ID NO: 2860 -1.2 -28.3 80 -26.2 -0.8 -5.8 ATGGCCTGCGGTCCAGTCTC

1431 SEQ ID NO:2861 -1.2 -30.9 85.7 -28 -1.7 -9.9 CAGAAGGGTTCTGTGAATGC

2638 SEQ ID NO: 2862 -1.2 -22.5 66.8 -19.3 -2 -6.7 TTATGCTCCAACAGAAACCA

2701 SEQ ID NO: 2863 -1.2 -21.9 62.5 -20.7 0 -3.6 CATGGTTCTGAGTTGGATCT

2743 SEQ ID NO: 2864 -1.2 -23.5 70.9 -22.3 0 -5 AATCTAAGGCAGATTTTTAA

2887 SEQ ID NO:2865 -1.2 -17.3 54.9 -14.5 -1.6 -5.6 CTGTTGGCCTTTACACAGAG

3008 SEQ ID NO: 2866 -1.2 -24.4 71 -22.5 -0.5 -6.5 ATATAATACATGTACTCTCA

3396 SEQ ID NO: 2867 -1.2 -17.7 56.5 -16 0 -8.2 TAGCCAACACTTAAAGCAAA

3541 SEQ ID NO:2868 -1.2 -19 56.4 -17.1 -0.4 -4.1 TCATGGGCTTGCATTGTCCT

8 SEQ ID NO: 2869 -1.1 -27.4 78.3 -25.6 -0.5 -8 TGGTTTCCGAGAGCCTAAAC

336 SEQ ID NO: 2870 -1.1 -24.2 68 -22.5 -0.3 -5.2 TCAACAAAAACCAGAGAGAG

596 SEQ ID NO: 2871 -1.1 -17.2 53.1 -16.1 0 -2.4 CCACGGGGAAGACAGTGGGT

1090 SEQ ID NO: 2872 -1.1 -27.5 74.9 -24.7 -1.7 -6 GCAGCTCTGGCCTTTTCGCC

2038 SEQ ID NO: 2873 -1.1 -31.7 86.2 -29.5 -1 -7.2 TGGAACTGTGCCATTTCCTC

2129 SEQ ID NO: 2874 -1.1 -25.8 73.3 -22.4 -2.3 -9.8 AGATTGTGGAACTGTGCCAT

2135 SEQ ID NO: 2875 -1.1 -23.8 68.8 -21.9 -0.6 -4.6 TGAGCATGGCTGATCCAGGT

2940 SEQ ID NO: 2876 -1.1 -27.1 77.1 -24.5 -1.4 -6.9 CACATTAAAAATCTGTTGGC

3020 SEQ ID NO: 2877 -1.1 -18.2 55.9 -17.1 0 -3 CAGATTTCTACATCCTAGAA

3227 SEQ ID NO: 2878 -1.1 -20.3 61.7 -18.2 -0.9 -4.9 ACTTTAAAAAATCCCTGGAG

3273 SEQ ID NO: 2879 -1.1 -18.6 55.7 -17.5 0 -4.8

179 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

AAAGACTCACAATAAAGTGA 3316 SEQ ID NO:2880 -1.1 -15.7 50.7 -13.3 -1.2 -5.6

GAACAGCTCATGGGCTTGCA 15 SEQ ID NO: 2881 -1 -26.3 74.5 -23.5 -1.6 -11

GCTCCGAAGCCCATAAGCGT 98 SEQ ID NO: 2882 -1 -29.1 75.5 -27 -1 -6.1

TATGAAAGCCATTCATAGGG 362 SEQ ID NO: 2883 -1 -20.7 61.3 -17 -2.7 -8.8

AGATGCCAATGAACTGATCT 451 SEQ ID NO: 2884 -1 -21.3 62.4 -20.3 0 -4.9

TTTCCAAGGGTATCATAAAG 542 SEQ ID NO:2885 -1 -19.3 58.8 -18.3 0 -3.6

TGGCTTGTCAACAAAAACCA 603 SEQ ID NO:2886 -1 -20.6 59.5 -18.7 -0.7 -6.4

GCTGGTGACTTCCACCCCAC 735 SEQ ID NO:2887 -1 -31.1 83 -27.1 -3 -8.8

TGTAGTTCCACTTGTGAAAC 834 SEQ ID NO:2888 -1 -21.1 63.7 -19.4 -0.5 -5.1

AGATATCAAAGTATCATCTG

948 SEQ ID NO:2889 -1 -17.3 55.6 -14.8 -1.4 -6.9 TCAGCCGGTCCCACAGGCTG

1240 SEQ ID NO:2890 -1 -32 84.8 -25.7 -5.3 -12.9

CCATCAGCCGGACTCTTCCG 1288 SEQ ID NO:2891 -1 -29.9 78.4 -26.2 -2.7 -9.2

TTCAAATGGTTTCAGACCAG 1947 SEQ ID NO: 2892 -1 -21 62.7 -17.5 -2.5 -6.5

AACCTTATGCTCCAACAGAA 2705 SEQ ID NO:2893 -1 -22.1 63.1 -21.1 0 -3.6

TCTGAGTTGGATCTGCCCTC 2737 SEQ ID NO: 2894 -1 -27.4 79.1 -25.9 -0.2 -5

CTCGTGGCGTACCAGAAGGT 134 SEQ ID NO:2895 -0.9 -27.2 74.7 -24.7 -1.6 -9.6

ACCACTACCCGCCACTTCCA 198 SEQ ID NO:2896 -0.9 -31.5 80.2 -30.6 0 -2.6

CCTGTATTCCCCTCTGGAAA 298 SEQ ID NO:2897 -0.9 -26.9 73.2 -24 -2 -5.6

GTTTATATGAAAGCCATTCA 367 SEQ ID NO:2898 -0.9 -19.7 59.8 -17.2 -1.5 -6.4

CAAAGATGCCAATGAACTGA 454 SEQ ID NO:2899 -0.9 -19.3 56.8 -18.4 0 -3

AAGCAAAGCATCCTTGTTCA 502 SEQ ID NO:2900 -0.9 -22.7 66 -20.9 -0.7 -4.4

ATCGAATAAGCAAAGCATCC 509 SEQ ID NO: 2901 -0.9 -20.1 58.7 -18.3 -0.7 -5.9

CTCTGGCTTGTCAACAAAAA

606 SEQ ID NO: 2902 -0.9 -19.9 59.1 -18.1 -0.8 -5.4 TCTCTGGCTTGTCAACAAAA

607 SEQ ID NO: 2903 -0.9 -21 62.4 -19.2 -0.8 -5.4 AAGATATCAAAGTATCATCT

949 SEQ ID NO:2904 -0.9 -16.6 53.8 -14.2 -1.4 -6.9 CTGATATCTCCTTGGAAAAA

1040 SEQ ID NO:2905 -0.9 -18.9 57 -18 0 -6.4

CACTCTGTCTGTCCGTATCC 1382 SEQ ID NO:2906 -0.9 -27.3 78.4 -26.4 0 -2.6

ACATGGCCTGCGGTCCAGTC 1433 SEQ ID NO:2907 -0.9 -30.5 83.4 -27.9 -1.7 -9.9

GCCATTTGGTAACCATTTTC 1638 SEQ ID NO: 2908 -0.9 -23.7 68.4 -22.1 -0.4 -6

GCTTTCTCCGTGGACAAACA 1770 SEQ ID NO: 2909 -0.9 -24.8 69.4 -23.9 0 -5.6

CTGAAATAGTTCCGCAGCTC 2051 SEQ ID NO: 2910 -0.9 -23.9 68.4 -22.3 -0.5 -5.6

180 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular posi tion oligo binding ation Duplex ture oligo oligo

GCAGGGATTTAAAAAGATCT

2600 SEQ ID NO : 2911 -0.9 -18.5 56.7 -17.6 0.6 -6.1 ATAAAGTAGACAGTTATTCA

2971 SEQ ID NO:2912 -0.9 -16.9 54.9 -16 0 -2.9

ACATTTCATAGAAATCAGGT 3191 SEQ ID NO: 2913 -0.9 -18.6 58.1 -16.4 -1.2 -6.1

AAGCCCTTCTGGATCAGTGC 419 SEQ ID NO: 2914 -0.8 -27.3 77.4 -25.9 -0.3 -5.3

TGTTCAATAATCACCCACTC 488 SEQ ID NO: 2915 -0.8 -22.2 64.8 -21.4 0 -2.2

GCTTTGTTGACTATGTACGT 572 SEQ ID NO: 2916 -0.8 -22.7 67.7 -21.9 0 -5.2

CAGCTTTGTTGACTATGTAC 574 SEQ ID NO: 2917 -0.8 -21.4 65.6 -20.6 0 -4.5

CTATGATTTTAAGGCCTGGT 667 SEQ ID NO:2918 -0.8 -22.8 66.9 -21.3 0 -8.7

AGATCTTCAGGTGCTGGAGG 803 SEQ ID NO:2919 -0.8 -25.2 75.2 -23 -1.3 -8.3

CATGAGCAGCCTGATATCTC 1050 SEQ ID NO: 2920 -0.8 -24.5 71.6 -23.7 0 -6.4

TCCATGAGCAGCCTGATATC 1052 SEQ ID NO: 2921 -0.8 -25.6 73.3 -24.8 0 -5.4

AGTGGGTTGAAGCACCTTGA 1077 SEQ ID NO: 2922 -0.8 -25.1 72.3 -23.3 -0.9 -4.7

GGCATGGTTAGGCAGCACCC 1409 SEQ ID NO:2923 -0.8 -30.3 83.2 -28.6 -0.8 -5.8

GGGTTCTGTGAATGCCTGTG 2633 SEQ ID NO:2924 -0.8 -26 75 -25.2 0 -4.7

GTAGACAGTTATTCAGGCGT 2966 SEQ ID NO:2925 -0.8 -23.6 70.7 -22.8 0 -4

AAAAATCTGTTGGCCTTTAC 3014 SEQ ID NO:2926 -0.8 -19.8 59.3 -19 0 -7.2

AGCCAACACTTAAAGCAAAC 3540 SEQ ID NO:2927 -0.8 -19.5 57.4 -18 -0.4 -4.1

CGAAAATACCGGAACAGCTC 26 SEQ ID NO: 2928 -0.7 -21.1 59.2 -20.4 0 -7.1

GTGCTGGAGGCTTGGGCTTC 793 SEQ ID NO: 2929 -0.7 -29.3 84.6 -27.1 -1.4 -6.4

AAACAAATTACTGCAAGATC 818 SEQ ID NO: 2930 -0.7 -15.8 50.7 -14.6 -0.2 -4.9

AGAGGCAAGAAAGATATCAA 959 SEQ ID NO:2931 -0.7 -17.5 54.6 -16.8 0 -6.9

AAGCACCTTGAGGTCATCCA 1068 SEQ ID NO:2932 -0.7 -26.2 74.1 -24.2 -1.2 -7.5

GAAGATCAGCCGGTCCCACA 1245 SEQ ID NO:2933 -0.7 -28.6 76.5 -27.9 0 -6.7

GCACAGTGGCAGACACCGGG 1321 SEQ ID NO:2934 -0.7 -29.2 78.7 -27.6 -0.8 -7.2

GCACTCTGTCTGTCCGTATC 1383 SEQ ID NO:2935 -0.7 -27.1 79.4 -26.4 0 -3.4

CCTTCAAATCCTCTCTTTTG 1850 SEQ ID NO:2936 -0.7 -22.9 67 -21.6 -0.3 -3.6

AGCAGGGATTTAAAAAGATC

2601 SEQ ID NO:2937 -0.7 -17.6 55 -16.9 0 -5 AGTAGCAGGGATTTAAAAAG

2604 SEQ ID NO:2938 -0.7 -17.5 54.9 -16.8 0 -5

CCTTATGCTCCAACAGAAAC

2703 SEQ ID NO: 2939 -0.7 -22.1 63.1 -21.4 0 -3.6

TGGTTCTGAGTTGGATCTGC

2741 SEQ ID NO:2940 -0.7 -24.6 74.3 -23.9 0 -5

CACGCGTTCTGATGAGCACC

2787 SEQ ID NO:2941 -0.7 -26.8 73.1 -25.1 -0.4 -9.8

181 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

AGTGAAGATAAAGTAGACAG 2978 SEQ ID NO: 2942 -0.7 -16.4 53.2 -15.7 0 -2.8

TGACTTTTTGTGCAATTAAG 3493 SEQ ID NO:2943 -0.7 -18.2 57 -17.5 0 -7.3

AAACATAGAAATAGCCAACA 3552 SEQ ID NO:2944 -0.7 -16.8 52 -16.1 0 -3.2

CCCTCTGGAAACCTTCGTAT 289 SEQ ID NO:2945 -0.6 -25.9 70.5 -24.4 -0.8 -3.8

ATCCTTGTTCAATAATCACC 493 SEQ ID NO:2946 -0.6 -21.4 63.4 -20.8 0 -3.4

TTCCAAGGGTATCATAAAGT 541 SEQ ID NO: 2947 -0.6 -20.4 61.5 -19.8 0 -3.6

GATCTTCAGGTGCTGGAGGC 802 SEQ ID NO: 2948 -0.6 -27 79.6 -25 -1.3 -6.3

GGGTTGCCTGTAGTTCCACT 842 SEQ ID NO: 2949 -0.6 -28.8 82.5 -27.7 -0.2 -3.8

TATCAAAGTATCATCTGGGC 945 SEQ ID NO:2950 -0.6 -20.9 63.6 -20.3 0 -2.8

ATCCATGAGCAGCCTGATAT 1053 SEQ ID NO:2951 -0.6 -25.2 71.6 -24.6 0 -4.5

TTCTGATGATGCCGCTGCGA 1216 SEQ ID NO:2952 -0.6 -27.1 73.2 -24.9 -1.6 -9.6

GTGGCAGACACCGGGGCGGC 1316 SEQ ID NO: 2953 -0.6 -32.6 84.4 -30.3 -1.7 -7.3

CCCGGCAGTGCACTCTGTCT 1392 SEQ ID NO: 2954 -0.6 -31.1 84.8 -29 -1.3 -10.2

TTAGGCAGCACCCGGCAGTG 1402 SEQ ID NO: 2955 -0.6 -29.9 80.5 -27.7 -1.5 -7.4

ATTTTCCAATGTCCCCTGTG 1624 SEQ ID NO:2956 -0.6 -26.4 73.4 -25.8 0 -2.2

ACCACAATTGCAATGAGAAA 1799 SEQ ID NO:2957 -0.6 -18.8 55.9 -17.4 0 -9.3

GTTCTGTGAATGCCTGTGAG 2631 SEQ ID NO:2958 -0.6 -24.2 71.3 -23.6 0 -5.1

AGGCTCCTTATCTGCATGGT 2757 SEQ ID NO: 2959 -0.6 -27.2 78.8 -25.7 -0.7 -5

GAATCCACGCGTTCTGATGA 2792 SEQ ID NO: 2960 -0.6 -24.4 67.8 -23.1 0 -9.1

GAGAACCGAGTCCAAGAGCA 2827 SEQ ID NO:2961 -0.6 -24.8 68.9 -24.2 0 -4.1

GAGCATGGCTGATCCAGGTA 2939 SEQ ID NO:2962 -0.6 -26.8 76.7 -24.7 -1.4 -6.9

AAATCAGGTAGCATTATAAG 3180 SEQ ID NO:2963 -0.6 -17.1 54.5 -16.5 0 -4.4

TTGTGACATCATCATAGAAA 265 SEQ ID NO: 2964 -0.5 -17.9 56.2 -16.6 -0.6 -3.9

GCAAAGATGCCAATGAACTG 455 SEQ ID NO:2965 -0.5 -20.5 59.2 -18.5 -1.4 -6.4

TTTGAGCAAAGATGCCAATG 460 SEQ ID NO: 2966 -0.5 -20.3 59.6 -16.9 -2.9 -7.3

CAAAGCATCCTTGTTCAATA 499 SEQ ID NO: 2967 -0.5 -20.6 61.2 -19.6 -0.2 -4.1

ACCCTCTAATAAGAGTTTGG 630 SEQ ID NO:2968 -0.5 -21.6 63.8 -19.2 -1.9 -6.5

GCTGGAGGCTTGGGCTTCCG 791 SEQ ID NO:2969 -0.5 -30.9 83.9 -26.2 -4.2 -10.5

TTGTGAAACAAATTACTGCA 823 SEQ ID NO: 2970 -0.5 -17.4 54 -15.2 -1.7 -8.1

TTTCACAAAAGCTGAACAAT 900 SEQ ID NO:2971 -0.5 -16.9 52.7 -15.8 -0.3 -5.1

ATCAAAGTATCATCTGGGCA 944 SEQ ID NO:2972 -0.5 -21.9 65.4 -21.4 0 -4

182 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GTGGGTTGAAGCACCTTGAG 1076 SEQ ID NO:2973 -0.5 -25.1 72.3 -23.6 -0.9 -4.7

AGGCTGTTGTTTCTGATGAT 1226 SEQ ID NO:2974 -0.5 -23.1 70 -22.6 0 -3.7

TCCTTCATAAAACTGACAGC 1365 SEQ ID NO:2975 -0.5 -20.5 60.9 -20 0 -4.1

GGTTAGGCAGCACCCGGCAG 1404 SEQ ID NO:2976 -0.5 -31.1 83.2 -29 -1.5 -6.1

ATGGTTTCAGACCAGAATCC 1942 SEQ ID NO:2977 -0.5 -23.5 68.4 -20.5 -2.5 -7

TGAGCTTTCTTCTTCACACT

2109 SEQ ID NO: 2978 -0.5 -23.4 71 -22.9 0 -5.2 CTGAGCTTTCTTCTTCACAC

2110 SEQ ID NO: 2979 -0.5 -23.4 71 -22.9 0 -5.2 TCTGAGCTTTCTTCTTCACA

2111 SEQ ID NO: 2980 -0.5 -23.6 72.1 -23.1 0 -5.2 AAGAGATTGTGGAACTGTGC

2138 SEQ ID NO: 2981 -0.5 -21 63.3 -19.8 -0.5 -4

ATGGTTCTGAGTTGGATCTG 2742 SEQ ID NO:2982 -0.5 -22.8 69.6 -22.3 0 -5

TAGCTTTAAAGAAATGCTTG 3105 SEQ ID NO:2983 -0.5 -16.9 53.5 -14.8 -1.5 -8.1

ATCCCAGGAAATGAACTTTC 3247 SEQ ID NO:2984 -0.5 -21.1 61.6 -19.6 -0.9 -4.9

GCTTGTATATAATACATGTA 3402 SEQ ID NO:2985 -0.5 -17.9 56.8 -15.8 -1.5 -7.9

CACTTAAAGCAAACATTCAA 3534 SEQ ID NO: 2986 -0.5 -16.7 52.3 -16.2 0 -4.1

TATGATTTTAAGGCCTGGTA 666 SEQ ID NO: 2987 -0.4 -21.6 64.4 -20.5 0 -8.7

AAGATCTTCAGGTGCTGGAG 804 SEQ ID NO: 2988 -0.4 -23.3 69.8 -22 -0.3 -9.5

ATGCCGCTGCGAAGCTCTGC 1208 SEQ ID NO: 2989 -0.4 -29.6 78.4 -26.7 -2.5 -10.2

AAGATCAGCCGGTCCCACAG 1244 SEQ ID NO:2990 -0.4 -28 75.6 -27.6 0 -6.7

ATGGTTAGGCAGCACCCGGC 1406 SEQ ID NO:2991 -0.4 -30.4 81.6 -29.3 -0.5 -6.1

CCTTGATTAGAAAAGCAGGG 2429 SEQ ID NO: 2992 -0.4 -20.8 61 -20.4 3.9 -4.1

GACAGCTGCAGAATTTGCAG 2487 SEQ ID NO: 2993 -0.4 -23.3 68 -19.4 -3.5 -11.8

CAGACAGCTGCAGAATTTGC 2489 SEQ ID NO: 2994 -0.4 -23.3 68 -21.4 -1.4 -8.9

GAATGCCTGTGAGAAGGGAC 2624 SEQ ID NO: 2995 -0.4 -23.5 67.5 -23.1 0.1 -3.2

CGGGGAATCAGGCCTGGAGA 2843 SEQ ID NO: 2996 -0.4 -27.7 75 -25.3 -0.2 -12.2

TATAGAATCTAAGGCAGATT 2892 SEQ ID NO: 2997 -0.4 -18 56.7 -16.1 -1.4 -5.8

AAAGGCAAGTTAATCCCAAC 3061 SEQ ID NO:2998 -0.4 -20.5 59.5 -20.1 0 -4

AATCAGGTAGCATTATAAGA 3179 SEQ ID NO: 2999 -0.4 -18.4 57.7 -18 0 -4.4

CTCACAATAAAGTGAACTGC 3311 SEQ ID NO: 3000 -0.4 -18.5 56.6 -16.6 -1.4 -5.9

TCTCGTGGCGTACCAGAAGG 135 SEQ ID NO: 3001 -0.3 -26.4 73.1 -24.8 -1.2 -5.4

ATCATCATAGAAATACACCA 258 SEQ ID NO: 3002 -0.3 -18.6 56.8 -18.3 0 -2.9

ACAAAAGCTGAACAATCGCT 896 SEQ ID NO: 3003 -0.3 -19.5 57 -17.7 -1.4 -5.1

183 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

AGGCAAGAAAGATATCAAAG 957 SEQ ID NO: 3004 -0.3 -16.2 51.6 -15.9 0 -6.9

GGAACGTCAGCACAGTGGCA 1330 SEQ ID NO:3005 -0.3 -26.7 74.7 -25.5 -0.8 -7.4

GGTCCAGTCTCCAGGCATGG 1422 SEQ ID NO: 3006 -0.3 -30 85.1 -28.5 -1.1 -8.8

CAACATGGCCTGCGGTCCAG 1435 SEQ ID NO:3007 -0.3 -28.9 76.7 -27.3 -1.2 -9.4

CAAACGACCCTTCAAATCCT 1858 SEQ ID NO:3008 -0.3 -23.1 63 -22.8 0 -3.5

CGAATGGACAAGTCAAACAC 2221 SEQ ID NO:3009 -0.3 -18.7 55.8 -18.4 0 -6.1

TTTAGAGCAGCAGACAGCTG 2499 SEQ ID NO:3010 -0.3 -23.7 70.5 -20.2 -3.2 -8.6

TATGCTCCAACAGAAACCAC 2700 SEQ ID NO:3011 -0.3 -22 62.7 -21.7 0 -3.6

TAAGGCAGATTTTTAAATAA 2883 SEQ ID NO: 3012 -0.3 -15 49.6 -14.1 -0.3 -4.5

CAGGCGTCACAGCTGAGCAT 2953 SEQ ID NO: 3013 -0.3 -27.5 77.2 -25.1 -2.1 -9.2

CACAATAAAGTGAACTGCTG 3309 SEQ ID NO:3014 -0.3 -18.1 55.3 -17.3 -0.1 -4.2

TAATACATGTACTCTCACAG 3393 SEQ ID NO:3015 -0.3 -18.9 59.1 -18.1 0 -8.2

AACAGCTCATGGGCTTGCAT 14 SEQ ID NO: 3016 -0.2 -25.7 73.1 -23.7 -1.6 -11

TTTATATGAAAGCCATTCAT 366 SEQ ID NO:3017 -0.2 -18.5 56.8 -16.4 -1.9 -7.5

GGCTTGTCAACAAAAACCAG 602 SEQ ID NO:3018 -0.2 -20.6 59.7 -20.4 0 -5.4

CTTCATGCTGGTGACTTCCA 741 SEQ ID NO:3019 -0.2 -26.1 75.2 -25.3 -0.3 -4.8

GGTCCCACAGGCTGTTGTTT 1234 SEQ ID NO:3020 -0.2 -29 82.6 -28.3 -0.1 -5

ACCAGAATCCTTCCCAAGTC 1932 SEQ ID NO: 3021 -0.2 -26.2 72.7 -25.5 -0.1 -2.8

AGGCCATTGTCGATAGAAAA

2000 SEQ ID NO: 3022 -0.2 -21 60.9 -19.5 -1.1 -9.7 AAGGCCATTGTCGATAGAAA

2001 SEQ ID NO: 3023 -0.2 -21 60.9 -19.5 -1.1 -9.7 ACTGTGCCATTTCCTCTGAG

2125 SEQ ID NO:3024 -0.2 -26.2 75.4 -26 0 -5.4

TGTCTTCACTATAGAATCTA 2901 SEQ ID NO:3025 -0.2 -19.1 60.6 -18.9 0 -6

ACATTAAAAATCTGTTGGCC 3019 SEQ ID NO:3026 -0.2 -19.5 58.3 -19.3 0 -6.2

AAAACCACATTAAAAATCTG 3025 SEQ ID NO:3027 -0.2 -14 46.6 -13.8 0 -3

TTAAAGCAAACATTCAAAAC 3531 SEQ ID NO:3028 -0.2 -13.7 46.3 -13.5 0 -3.3

CTGCAAAAGCTCCGAAGCCC 106 SEQ ID NO:3029 -0.1 -26.9 70.5 -25 -1.8 -8.1

CTTCGTGCACCACCACTACC 209 SEQ ID NO:3030 -0.1 -28.7 76.8 -27.8 -0.6 -8.4

TTCTGGATCAGTGCTGAGCC 413 SEQ ID NO: 3031 -0.1 -26.6 77.6 -26.5 3.1 -8.1

TAAGCAAAGCATCCTTGTTC 503 SEQ ID NO: 3032 -0.1 -21.7 64.3 -20.7 -0.7 -4.4

CCATCGAATAAGCAAAGCAT 511 SEQ ID NO: 3033 -0.1 -20.4 58.6 -19.4 -0.7 -5.9

GCCTTCATGCTGGTGACTTC 743 SEQ ID NO: 3034 -0.1 -27.2 78.6 -26.5 -0.3 -5.4

184 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

CCTGATATCTCCTTGGAAAA 1041 SEQ ID NO:3035 -0.1 -21.6 62.4 -21.5 0 -6.4

CCATGAGCAGCCTGATATCT 1051 SEQ ID NO:3036 -0.1 -26.1 73.5 -26 0 -6.4

CCGGCAGTGCACTCTGTCTG 1391 SEQ ID NO:3037 -0.1 -29.1 81.1 -27.5 -1.3 -10

CAGCCGTCTTTGTCCAAAGC 1598 SEQ ID NO:3038 -0.1 -26.7 74 -25.7 -0.7 -8.4

GAAATAGTTCCGCAGCTCTG 2049 SEQ ID NO:3039 -0.1 -23.9 68.4 -23.8 0 -4.6

ATTTGCAGCAAGTAGCAGAC 2475 SEQ ID NO: 3040 -0.1 -22.7 67.8 -21 -1.6 -8.5

TACGAATCAGAAGGGTTCTG 2645 SEQ ID NO:3041 -0.1 -20.6 61.5 -18.2 -2.3 -8.1

ATAGAATCTAAGGCAGATTT 2891 SEQ ID NO:3042 -0.1 -18.4 57.6 -16.1 -2.2 -6.6

AACCACATTAAAAATCTGTT

3023 SEQ ID NO: 3043 -0.1 -16.7 52.3 -16.6 0 -3 GCTCAATTCAGTCAAATGTG

3338 SEQ ID NO: 3044 -0.1 -20.4 62 -20.3 0 -2.8

AGTTCCACTTGTGAAACAAA 831 SEQ ID NO:3045 0 -19.5 58.5 -17.6 -1.9 -6.5

TGCTCTGAGGAACGTCAGCA 1338 SEQ ID NO:3046 0 -25.5 72.7 -24.3 -1.1 -6.5

• TTCAAATCCTCTCTTTTGGG 1848 SEQ ID NO:3047 0 -22.4 66.5 -21.5 -0.7 -4.9

TCTGTTGGCCTTTACACAGA 3009 SEQ ID NO:3048 0 -24.8 72.4 -23.3 -1.4 -7.5

AAACCACATTAAAAATCTGT

3024 SEQ ID NO: 3049 0 -15.9 50.4 -15.9 0 -3 CATAGAAATCAGGTAGCATT

3185 SEQ ID NO:3050 0 -19.4 59.6 -19.4 0 -4.1

GATTTCTACATCCTAGAATT 3225 SEQ ID NO:3051 0 -19.7 60.6 -18.2 -1.4 -4.9

CCCAGGAAATGAACTTTCCA 3245 SEQ ID NO:3052 0 -23.4 64.9 -19.6 -3.8 -8.2

GAAGCCCATAAGCGTGTTGG 93 SEQ ID NO: 3053 0.1 -25.7 70.6 -24.9 -0.7 -4.3

ATCTTCGTGCACCACCACTA 211 SEQ ID NO:3054 0.1 -26.9 74.4 -26.2 -0.6 -8.4

CCTCTAATAAGAGTTTGGCC 628 SEQ ID NO:3055 0.1 -23.2 67.4 -21.4 -1.9 -9.8

TGTGAAACAAATTACTGCAA 822 SEQ ID NO:3056 0.1 -16.6 52 -15.8 -0.8 -6.4

CAGTGGGTTGAAGCACCTTG 1078 SEQ ID NO:3057 0.1 -25.2 72.1 -24.3 -0.9 -4.2

CAGCCGGTCCCACAGGCTGT 1239 SEQ ID NO: 3058 0.1 -32.8 86.5 -27.9 -5 -12.3

CACAGTGGCAGACACCGGGG 1320 SEQ ID NO: 3059 0.1 -28.6 77 -27.1 -1.6 -7.3

TCTGAGGAACGTCAGCACAG 1335 SEQ ID NO:3060 0.1 -23.7 68.6 -22.6 -1.1 -5.7

CAGGCATGGTTAGGCAGCAC 1411 SEQ ID NO:3061 0.1 -27 77.4 -26.2 -0.8 -5.3

ATGTCCCCTGTGTGTAACCA 1616 SEQ ID NO: 3062 0.1 -28 77.2 -27.6 -0.1 -2.1

TTCAGACCAGAATCCTTCCC 1937 SEQ ID NO: 3063 0.1 -26.4 73.4 -26 -0.1 -3.5

GTAACCCTTACGAATCAGAA 2653 SEQ ID NO:3064 0.1 -21 60.5 -20.2 -0.7 -4.3

GTTTCGTAACCCTTACGAAT 2658 SEQ ID NO: 3065 0.1 -22.6 63.7 -18.1 -4.6 -11.4

185 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GCTCCTTATCTGCATGGTTC

2755 SEQ ID NO: 3066 0.1 -26.5 77.9 -26.6 0 -5 ACACATTTCATAGAAATCAG

3193 SEQ ID NO: 3067 0.1 -17.1 54.4 -15.9 -1.2 -6.1

AGATTTCTACATCCTAGAAT 3226 SEQ ID NO:3068 0.1 -19.6 60.5 -18.2 -1.4 -4.9

GACTCACAATAAAGTGAACT 3313 SEQ ID NO:3069 0.1 -17.5 54.6 -16.1 -1.4 -5.9

ACAAATGACAGCTCAATTCA 3348 SEQ ID NO:3070 0.1 -19.3 58.3 -19.4 0.2 -4.4

ATACATGTACTCTCACAGAC 3391 SEQ ID NO:3071 0.1 -20.7 63.8 -20.1 0 -9

GCTGCAAAAGCTCCGAAGCC 107 SEQ ID NO: 3072 0.2 -26.7 71 -25.1 -1.8 -9

GGTGGTGAGTGCTGCAAAAG

117 SEQ ID NO: 3073 0.2 -23.7 68.7 -23.4 0 -7.8 AGGTGGTGAGTGCTGCAAAA

118 SEQ ID NO: 3074 0.2 -23.7 68.7 -23.4 0 -7.8 CGTGCACCACCACTACCCGC

206 SEQ ID NO: 3075 0.2 -31.9 79.8 -31.3 -0.6 -8.4

TCTGCAACCTGTTTATATGA 377 SEQ ID NO:3076 0.2 -21.6 64.3 -21.8 0 -4.9

CTTTGTTGACTATGTACGTG 571 SEQ ID NO:3077 0.2 -20.9 63.3 -21.1 0 -5.2

CCCTCTAATAAGAGTTTGGC 629 SEQ ID NO:3078 0.2 -23.2 67.4 -21.5 -1.9 -6.4

GAGAGGCAAGAAAGATATCA 960 SEQ ID NO:3079 0.2 -18.8 57.7 -19 0 -6.9

GCCTGATATCTCCTTGGAAA 1042 SEQ ID NO: 3080 0.2 -24.1 68.4 -24.3 0 -6.4

ACGGGGAAGACAGTGGGTTG 1088 SEQ ID NO: 3081 0.2 -24.9 70.5 -25.1 0 -4.6

TGTTGTTTCTGATGATGCCG

1222 SEQ ID NO: 3082 0.2 -23.8 68.8 -24 0 -3.5 CAAATGGTTTCAGACCAGAA

1945 SEQ ID NO:3083 0.2 -20.4 60.3 -18.1 -2.5 -6.4

AAAAGCAGGGAGACAGAAGA

2419 SEQ ID NO:3084 0.2 -19.4 58.2 -19.6 0 -4.1

ACGAATCAGAAGGGTTCTGT

2644 SEQ ID NO:3085 0.2 -22.1 65.2 -19.7 -2.6 -8.7

GGCTCCTTATCTGCATGGTT

2756 SEQ ID NO:3086 0.2 -27.3 78.8 -26.6 -0.7 -5 TGATCCAGGTAACTCTTTCT

2930 SEQ ID NO: 3087 0.2 -23 68.8 -22.3 -0.8 -6.5

AAATCTGTTGGCCTTTACAC 3012 SEQ ID NO: 3088 0.2 -22.1 65 -22.3 0 -7.2

ACATGATCTTTTGATATGAA 3043 SEQ ID NO:3089 0.2 -17.3 55 -15.9 -1.6 -6.1

CAGGAAATGAACTTTCCAGA 3243 SEQ ID NO:3090 0.2 -20 59.3 -16.4 -3.8 -8.2

CAAATTATTGACTTTTTGTG 3501 SEQ ID NO:3091 0.2 -16.5 53.2 -16.2 -0.2 -3.5

GATGCCAATGAACTGATCTG 450 SEQ ID NO: 3092 0.3 -21.3 62.1 -21.6 0 -4.9

GCAAAGCATCCTTGTTCAAT 500 SEQ ID NO: 3093 0.3 -22.7 65.7 -22.5 -0.2 -4

TGACTATGTACGTGATGGCT 565 SEQ ID NO: 3094 0.3 -23 67.2 -23.3 0 -5.2

ATGCTGGTGACTTCCACCCC 737 SEQ ID NO:3095 0.3 -30.2 81.2 -28.2 -2.3 -9.2

CTGTTGTTTCTGATGATGCC

1223 SEQ ID NO:3096 0.3 -23.9 70.7 -24.2 0 -3.5

186 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCACAATTGCAATGAGAAAT 1798 SEQ ID NO:3097 0.3 -18.6 55.4 -18.2 0 -8.8

CAGACCAGAATCCTTCCCAA 1935 SEQ ID NO:3098 0.3 -25.9 70.4 -25.7 -0.1 -2.8

ATAGCAAAGTCCTAACCCCT 2446 SEQ ID NO:3099 0.3 -25.4 69.6 -25.7 0 -4.1

AAACCTTATGCTCCAACAGA 2706 SEQ ID NO:3100 0.3 -22.1 63.1 -22.4 0 -3.6

CCTCCCGCTTACTGGAAACC 2721 SEQ ID NO:3101 0.3 -28.3 73.7 -28.6 0 -3.5

AGGAAATGAACTTTCCAGAT 3242 SEQ ID NO:3102 0.3 -19.3 58.1 -15.8 -3.8 -8.2

CAATAAAGTGAACTGCTGTT 3307 SEQ ID NO:3103 0.3 -18.5 56.7 -18.1 -0.5 -7.6

ACATCATCATAGAAATACAC 260 SEQ ID NO:3104 0.4 -16.8 53.6 -17.2 0 -2.9

GAAACCTTCGTATAATGTTG

282 SEQ ID NO:3105 0.4 -18.8 56.9 -19.2 0 -3.1 GGAAACCTTCGTATAATGTT

283 SEQ ID NO:3106 0.4 -20 59.3 -19.5 -0.8 -3.8 CGAGAGCCTAAACAAGGGCC

329 SEQ ID NO: 3107 0.4 -25.4 68.5 -24.4 -1.3 -6.4

CTTGTCAACAAAAACCAGAG 600 SEQ ID NO:3108 0.4 -18.2 55.1 -18.6 0 -5.4

CCTTCATGCTGGTGACTTCC 742 SEQ ID NO:3109 0.4 -27.4 77.7 -27.2 -0.3 -4.4

GGTGCTGGAGGCTTGGGCTT 794 SEQ ID NO:3110 0.4 -30.1 85.4 -29.1 -1.3 -6.1

CCAACATGGCCTGCGGTCCA 1436 SEQ ID NO:3111 0.4 -30.9 79.7 -29.7 -1.5 -9.6

CCTGAAATACATTTGGCCCT 1546 SEQ ID NO:3112 0.4 -24.8 67.9 -25.2 0 -7.3

GTCTTTGTCCAAAGCTTCTG 1593 SEQ ID NO:3113 0.4 -23.7 70.5 -23.2 -0.7 -8.4

GTCCCCTGTGTGTAACCAGC 1614 SEQ ID NO:3114 0.4 -29.8 82.2 -29.2 -0.9 -3.3

TGGTAACCATTTTCCAATGT 1632 SEQ ID NO:3115 0.4 -22.2 64.5 -21.4 -1.1 -5.5

CTTCAAATCCTCTCTTTTGG 1849 SEQ ID NO:3116 0.4 -22.1 65.9 -21.6 -0.7 -3.9

TGGTTTCAGACCAGAATCCT 1941 SEQ ID NO:3117 0.4 -24.4 70.4 -22.7 -2.1 -6.9

AGGCAGATTTTTAAATAACC 2881 SEQ ID NO:3118 0.4 -18.2 56 -18 -0.3 -4.5

GCTGAGCATGGCTGATCCAG 2942 SEQ ID NO:3119 0.4 -27.4 77.3 -26.5 -1.2 -6.9

AGTTAATCCCAACATGATCT 3054 SEQ ID NO:3120 0.4 -21.5 63.1 -21.2 -0.5 -5.4

AAAGAAATGCTTGCCTGAGA 3098 SEQ ID NO:3121 0.4 -20.5 59.9 -20.3 -0.3 -3.9

AAGACTCACAATAAAGTGAA 3315 SEQ ID NO:3122 0.4 -15.7 50.7 -14.8 -1.2 -5.7

CCCATAAGCGTGTTGGTCGG 89 SEQ ID NO:3123 0.5 -27.6 74.3 -27.6 -0.2 -4.6

TGCAAAAGCTCCGAAGCCCA 105 SEQ ID NO:3124 0.5 -26.7 69.8 -25.4 -1.8 -7.9

GTGGTGAGTGCTGCAAAAGC 116 SEQ ID NO:3125 0.5 -24.3 70.4 -23.4 -1.3 -7.8

TGGAAACCTTCGTATAATGT

284 SEQ ID NO: 3126 0.5 -19.9 59 -19.5 -0.8 -3.5 TTGAGCAAAGATGCCAATGA

459 SEQ ID NO:3127 0.5 -20.8 60.5 -18.7 -2.6 -7.9

187 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CGGTCCCACAGGCTGTTGTT 1235 SEQ ID NO:3128 0.5 -29.7 81.6 -29.7 -0.1 -5

TCTTTGTCCAAAGCTTCTGC 1592 SEQ ID NO:3129 0.5 -24.3 71.4 -23.9 -0.7 -8.4

TCAAATGGTTTCAGACCAGA 1946 SEQ ID NO:3130 0.5 -21.5 63.7 -20 -2 -6.5

CGACCTGAAATAGTTCCGCA 2055 SEQ ID NO:3131 0.5 -24.4 66.4 -24.2 -0.5 -5.6

GAACCCCGAATGGACAAGTC 2227 SEQ ID NO:3132 0.5 -24.4 66.2 -24.9 0.1 -4.9

AGAATTTGCAGCAAGTAGCA 2478 SEQ ID NO: 3133 0.5 -21.8 64.9 -20.7 -1.6 -8.2

AAAGATCTCTGGTCCGCTTG 2588 SEQ ID NO:3134 0.5 -24.2 69.2 -24.7 0 -6.3

TTTCTACATCCTAGAATTTT 3223 SEQ ID NO:3135 0.5 -19.3 60 -18.3 -1.4 -4.2

AATACATATATGAAGTTAGG 3473 SEQ ID NO:3136 0.5 -15.4 50.9 -15.4 0 -8.2

GAAAATACCGGAACAGCTCA 25 SEQ ID NO:3137 0.6 -21 59.8 -21.6 0 -7.1

TGTATTCCCCTCTGGAAACC 296 SEQ ID NO:3138 0.6 -26.2 71.9 -24.8 -2 -5.9

TTCCGAGAGCCTAAACAAGG 332 SEQ ID NO:3139 0.6 -22.9 64.1 -22.5 -0.9 -8

AGCAAAGATGCCAATGAACT 456 SEQ ID NO:3140 0.6 -20.5 59.5 -18.9 -2.2 -6.4

CATCCTTGTTCAATAATCAC 494 SEQ ID NO:3141 0.6 -20.1 60.9 -20.7 0 -3.2

CAGGCTGTTGTTTCTGATGA 1227 SEQ ID NO:3142 0.6 -23.8 71.3 -24.4 0 -3.7

AGCCGGTCCCACAGGCTGTT 1238 SEQ ID NO:3143 0.6 -32.2 86 -29.3 -3.5 -10

ACAGTGGCAGACACCGGGGC 1319 SEQ ID NO:3144 0.6 -29.7 80.2 -28.7 -1.6 -7.3

TGGTTAGGCAGCACCCGGCA 1405 SEQ ID NO:3145 0.6 -31.1 82.6 -30.1 -1.5 -6.1

CTTTGTCCAAAGCTTCTGCT 1591 SEQ ID NO:3146 0.6 -24.8 71.8 -23.8 -1.5 -7.3

TCAGACCAGAATCCTTCCCA 1936 SEQ ID NO:3147 0.6 -27 74.1 -27.1 -0.1 -2.8

GGTTTCAGACCAGAATCCTT 1940 SEQ ID NO: 3148 0.6 -24.5 70.9 -23.6 -1.4 -6.2

GACCTGAAATAGTTCCGCAG 2054 SEQ ID NO: 3149 0.6 -23.6 66.4 -24.2 0.2 -4.9

AGGGATTTAAAAAGATCTCT 2598 SEQ ID NO:3150 0.6 -17.3 54.7 -17.2 -0.4 -6.3

AATCCACGCGTTCTGATGAG 2791 SEQ ID NO:3151 0.6 -23.8 66.8 -23.7 0 -8.9

AACTTTAAAAAATCCCTGGA 3274 SEQ ID NO:3152 0.6 -17.9 53.9 -18.5 0 -4.5

AATAAAGTGAACTGCTGTTA 3306 SEQ ID NO:3153 0.6 -17.5 54.9 -17.2 -0.7 -7.7

ATATGAAAGCCATTCATAGG 363 SEQ ID NO:3154 0.7 -19.5 58.8 -17 -3.2 -9.7

ACCTGTTTATATGAAAGCCA 371 SEQ ID NO: 3155 0.7 -21.6 62.9 -22.3 0 -3.2

AGACAGCTGCAGAATTTGCA 2488 SEQ ID NO:3156 0.7 -23.3 68 -21.5 -2.5 -9

AGCTTTAAAGAAATGCTTGC 3104 SEQ ID NO:3157 0.7 -19 57.9 -18.3 -1.3 -8.1

ACAATAAAGTGAACTGCTGT 3308 SEQ ID NO:3158 0.7 -18.6 56.9 -19.3 0 -5.4 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

TGTTTATATGAAAGCCATTC 368 SEQ ID NO:3159 0.8 -19 58.5 -19.3 -0.2 -3.8

TCTGGATCAGTGCTGAGCCT 412 SEQ ID NO: 3160 0.8 -27.4 79.2 -27.6 2.3 -9.1

CTTGTGAAACAAATTACTGC 824 SEQ ID NO: 3161 0.8 -17.6 54.6 -16.5 -1.9 -6.3

CACAGGCTGTTGTTTCTGAT 1229 SEQ ID NO:3162 0.8 -24.1 71.9 -24.2 -0.5 -4.9

CAATGTCCCCTGTGTGTAAC 1618 SEQ ID NO: 3163 0.8 -25.3 71.3 -26.1 0 -1.8

CACAATTGCAATGAGAAATG 1797 SEQ ID NO:3164 0.8 -16.6 51.9 -16.6 0 -9.3

TCAAACGACCCTTCAAATCC 1859 SEQ ID NO:3165 0.8 -22.6 62.5 -23.4 0 -2.6

CTGCGACCTGAAATAGTTCC 2058 SEQ ID NO:3166 0.8 -23.8 66.7 -23.9 -0.5 -5.6

AGGGTTCTGTGAATGCCTGT 2634 SEQ ID NO: 3167 0.8 -26 75.5 -26.3 -0.2 -4.7

TCACAGCTGAGCATGGCTGA

2947 SEQ ID NO:3168 0.8 -26.3 75.5 -23.9 -3.2 -9.9 GTCACAGCTGAGCATGGCTG

2948 SEQ ID NO: 3169 0.8 -26.9 77.7 -24.9 -2.8 -9.8 ATAAAGTGAACTGCTGTTAA

3305 SEQ ID NO:3170 0.8 -17.5 54.9 -17.4 -0.7 -7.7

AGACTCACAATAAAGTGAAC 3314 SEQ ID NO:3171 0.8 -16.6 52.9 -15.9 -1.4 -5.9

AATACATGTACTCTCACAGA 3392 SEQ ID NO:3172 0.8 -19.8 61 -20.1 0 -8.2

CCGAGAGCCTAAACAAGGGC 330 SEQ ID NO: 3173 0.9 -25.4 68.5 -24.7 -1.5 -5.8

TCCACTTGTGAAACAAATTA 828 SEQ ID NO:3174 0.9 -18 55.1 -17.2 -1.7 -5.4

ACCACGGGGAAGACAGTGGG 1091 SEQ ID NO:3175 0.9 -26.5 72.3 -24.8 -2.6 -7.5

TGTCCCCTGTGTGTAACCAG 1615 SEQ ID NO: 3176 0.9 -28 77.6 -27.6 -1.2 -3.5

CACAGTTCCTCAAACGACCC 1868 SEQ ID NO:3177 0.9 -25.7 69.7 -25.2 -1.3 -3.9

AATGGTTTCAGACCAGAATC

1943 SEQ ID NO: 3178 0.9 -20.8 62.5 -19.2 -2.5 -6.6 AAATGGTTTCAGACCAGAAT

1944 SEQ ID NO: 3179 0.9 -19.7 59.1 -18.1 -2.5 -6.4 CTTACGAATCAGAAGGGTTC

2647 SEQ ID NO:3180 0.9 -20.7 62 -21.6 0 -3.5

ATGCTCCAACAGAAACCACA 2699 SEQ ID NO:3181 0.9 -23 64.3 -23.9 0 -3.6

GAATCTAAGGCAGATTTTTA 2888 SEQ ID NO: 3182 0.9 -18.6 58.1 -17.3 -2.2 -6.6

AACATGATCTTTTGATATGA 3044 SEQ ID NO: 3183 0.9 -17.3 55 -16.6 -1.6 -6.1

TCGTGGCGTACCAGAAGGTG 133 SEQ ID NO: 3184 1 -26.3 72.7 -24.9 -2.4 -9.6

AGCACCCGGCAGTGCACTCT 1396 SEQ ID NO:3185 1 -31.3 84 -28.7 -3.6 -13.3

GTTTCAGACCAGAATCCTTC 1939 SEQ ID NO: 3186 1 -23.7 69.9 -24.7 0 -3.6

ATCTGCGACCTGAAATAGTT 2060 SEQ ID NO: 3187 1 -21.8 63.2 -22.8 0 -4.5

CAGGGATTTAAAAAGATCTC 2599 SEQ ID NO: 3188 1 -17.1 54.1 -17.6 -0.2 -6.3

AGAACATGAGTTTCGTAACC 2667 SEQ ID NO:3189 1 -20.4 60.9 -20.5 -0.8 -7.3

189 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TCACTATAGAATCTAAGGCA

2896 SEQ ID NO: 3190 1 -19.5 60 -20.5 0 -6 GTCTTCACTATAGAATCTAA

2900 SEQ ID NO: 3191 1 -18.4 58.5 -19.4 0 -6 CCAACATGATCTTTTGATAT

3046 SEQ ID NO: 3192 1 -19.4 58.8 -19.3 -1 -6.1 AGAAATCAGGTAGCATTATA

3182 SEQ ID NO: 3193 1 -18.4 57.7 -19.4 0 -4.1 TAGAAATCAGGTAGCATTAT

3183 SEQ ID NO: 3194 1 -18.4 57.7 -19.4 0 -4.1 CCCTTCTGGATCAGTGCTGA

416 SEQ ID NO: 3195 1.1 -27.7 78.4 -28 -0.2 -9.1 GCCCTTCTGGATCAGTGCTG

417 SEQ ID NO: 3196 1.1 -28.9 81.5 -29.4 -0.3 -6.7 CAATGAACTGATCTGGGGCA

445 SEQ ID NO: 3197 1.1 -23 65.8 -24.1 0 -4.9 CCACTTGTGAAACAAATTAC

827 SEQ ID NO: 3198 1.1 -17.8 54.4 -17 -1.9 -5.4 TCTGATGATGCCGCTGCGAA

1215 SEQ ID NO: 3199 1.1 -26.3 70.7 -26 -1.3 -9.6 CTCAAACGACCCTTCAAATC

1860 SEQ ID NO: 3200 1.1 -21.5 60.9 -22.6 0 -3.5 TGAAATAGTTCCGCAGCTCT

2050 SEQ ID NO: 3201 1.1 -23.9 68.4 -24.3 -0.5 -5.6 CTGTGAGAAGGGACAGTAGC

2618 SEQ ID NO: 3202 1.1 -23.2 69.3 -23.4 -0.7 -4.3 AAGGCAGATTTTTAAATAAC

2882 SEQ ID NO: 3203 1.1 -15.5 50.6 -16 -0.3 -4.5 TTCTACATCCTAGAATTTTG

3222 SEQ ID NO: 3204 1.1 -19.2 59.6 -19.1 -1.1 -3.8 GACTTTTTGTGCAATTAAGA

3492 SEQ ID NO: 3205 1.1 -18.8 58.3 -19.4 0 -7.8 CGGATCTTCGTGCACCACCA

214 SEQ ID NO: 3206 1.2 -28.7 76 -29.2 -0.4 -8.4 CCTTCTCTGGCTTGTCAACA

610 SEQ ID NO: 3207 1.2 -26.1 75.2 -26.4 -0.8 -4.3 GTGACTTCCACCCCACACCT

731 SEQ ID NO: 3208 1.2 -31 81.4 -31.5 -0.5 -4.4 TGGGTTGAAGCACCTTGAGG

1075 SEQ ID NO: 3209 1.2 -25.1 71.5 -25.3 -0.9 -5.9 CGGGGAAGACAGTGGGTTGA

1087 SEQ ID NO:3210 1.2 -25.3 71.3 -26.5 0 -4.6 CGAAGCTCTGCTTCTTTCCT

1199 SEQ ID NO: 3211 1.2 -26.3 74.7 -23.8 -3.7 -10.4 AGATCAGCCGGTCCCACAGG

1243 SEQ ID NO: 3212 1.2 -29.9 80.5 -30 -0.4 -10 TTTCAGACCAGAATCCTTCC

1938 SEQ ID NO: 3213 1.2 -24.5 70.2 -25.2 -0.1 -3.7 TGCGACCTGAAATAGTTCCG

2057 SEQ ID NO: 3214 1.2 -23.7 65.2 -24.2 -0.5 -5.6 ACAGCTGCAGAATTTGCAGC

2486 SEQ ID NO: 3215 1.2 -24.5 70.9 -19.2 -6.5 -17.1 TCCCTCTAGTGCACTGTACT

2520 SEQ ID NO: 3216 1.2 -27.1 78.5 -27 0 -10.6 CTATAGAATCTAAGGCAGAT

2893 SEQ ID NO:3217 1.2 -18.8 58.3 -19 -0.9 -5.6 CAATTAAGAATACATATATG

3481 SEQ ID NO: 3218 1.2 -13 45.4 -13.7 0 -7.7 TGCTGCAAAAGCTCCGAAGC

108 SEQ ID NO: 3219 1.3 -24.7 67.6 -23.9 -2.1 -9.9 CATGCTGGTGACTTCCACCC

738 SEQ ID NO: 3220 1.3 -28.9 78.8 -27.2 -3 -9.2

190 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

TAGTTCCACTTGTGAAACAA 832 SEQ ID NO: 3221 1.3 -19.9 59.9 -19.5 -1.7 -6.3

CAAGAAAGATATCAAAGTAT 954 SEQ ID NO: 3222 1.3 -14.1 47.6 -15.4 0 -6.9

ACAGGCTGTTGTTTCTGATG 1228 SEQ ID NO:3223 1.3 -23.4 70.5 -24 -0.5 -4.6

GCGACCTGAAATAGTTCCGC 2056 SEQ ID NO:3224 1.3 -25.5 69.1 -25.6 -1.1 -7.2

GGACTGGAGAAGAACATGAG 2677 SEQ ID NO:3225 1.3 -20 60 -21.3 0 -5.2

GGTTTCCGAGAGCCTAAACA 335 SEQ ID NO:3226 1.4 -24.9 69.3 -24.8 -1.4 -6.2

CGATCACCATCGAATAAGCA 517 SEQ ID NO:3227 1.4 -22 61.7 -21.8 -1.6 -7.3

GCTGTTGTTTCTGATGATGC

1224 SEQ ID NO:3228 1.4 -23.7 71.4 -25.1 0 -2.8 TGCAGAATTTGCAGCAAGTA

2481 SEQ ID NO:3229 1.4 -21.8 64.6 -20.7 -2.5 -9.1

ACCACATTAAAAATCTGTTG 3022 SEQ ID NO:3230 1.4 -17.4 53.9 -18.8 0 -3

ATAGAAATCAGGTAGCATTA 3184 SEQ ID NO:3231 1.4 -18.4 57.7 -19.8 0 -4.1

GGGTATCATAAAGTGGAACG 535 SEQ ID NO: 3232 1.5 -20 59.5 -20.5 -0.9 -3.8

GATGGCTTCATTTCCAAGGG 552 SEQ ID NO: 3233 1.5 -24.7 71 -25.3 -0.7 -6.4

CTTCTCTGGCTTGTCAACAA 609 SEQ ID NO: 3234 1.5 -23.4 69.1 -24 -0.8 -5.1

GGCTGTTGTTTCTGATGATG

1225 SEQ ID NO:3235 1.5 -23.1 69.6 -24.6 0 -3.7 CCAATGTCCCCTGTGTGTAA

1619 SEQ ID NO:3236 1.5 -27.1 74.2 -28.6 0 -2.2

GTAACCATTTTCCAATGTCC 1630 SEQ ID NO:3237 1.5 -23.4 67.2 -24.1 -0.6 -4.3

GAACTGTGCCATTTCCTCTG 2127 SEQ ID NO:3238 1.5 -25.5 72.6 -27 0 -4.6

AATTTGCAGCAAGTAGCAGA 2476 SEQ ID NO: 3239 1.5 -21.8 64.9 -21.7 -1.6 -8.5

ACTATAGAATCTAAGGCAGA 2894 SEQ ID NO:3240 1.5 -19 58.9 -20.5 0 -6

AGTAGACAGTTATTCAGGCG 2967 SEQ ID NO: 3241 1.5 -22.4 67.5 -23.9 0 -4

GCAAAAGCTCCGAAGCCCAT 104 SEQ ID NO: 3242 1.6 -26.7 69.9 -26.5 -1.8 -6.6

CTTCTGGATCAGTGCTGAGC 414 SEQ ID NO: 3243 1.6 -25.5 75.9 -26.5 -0.3 -4.3

TGAGCAAAGATGCCAATGAA 458 SEQ ID NO:3244 1.6 -20 58.4 -19.4 -2.2 -7.5

CTGGTGACTTCCACCCCACA 734 SEQ ID NO:3245 1.6 -30 79.8 -28.6 -3 -7.5

AGTGGCAGACACCGGGGCGG 1317 SEQ ID NO:3246 1.6 -30.8 80.6 -30.7 -1.7 -7.3

AACATGGCCTGCGGTCCAGT 1434 SEQ ID NO: 3247 1.6 -29.4 79 -29.3 -1.7 -9.9

AAATAGTTCCGCAGCTCTGG 2048 SEQ ID NO: 3248 1.6 -24.5 69.6 -26.1 0 -5

GCAGACAGCTGCAGAATTTG 2490 SEQ ID NO:3249 1.6 -23.3 68 -21.4 -3.5 -10.7

CGTAACCCTTACGAATCAGA 2654 SEQ ID NO:3250 1.6 -22.5 62.8 -21.9 -2.2 -7.1

ACCTTATGCTCCAACAGAAA 2704 SEQ ID NO:3251 1.6 -22.1 63.1 -23.7 0 -3.6

191 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo GGGGAATCAGGCCTGGAGAA

2842 SEQ ID NO: 3252 1.6 -26.2 72.8 -25.8 -0.2 -12.2 GCCCATAAGCGTGTTGGTCG

90 SEQ ID NO: 3253 1.7 -28.2 76 -29.4 -0.2 -4.6 AAAGATGCCAATGAACTGAT

453 SEQ ID NO: 3254 1.7 -18.6 55.6 -20.3 0 -3 AGGAACGTCAGCACAGTGGC

1331 SEQ ID NO: 3255 1.7 -26 73.9 -27.7 0 -6.1 ACAATTGCAATGAGAAATGC

1796 SEQ ID NO: 3256 1.7 -17.7 54.3 -18.3 -0.9 -9.3 CAGAATTTGCAGCAAGTAGC

2479 SEQ ID NO: 3257 1.7 -21.8 64.9 -22.7 -0.5 -8.5 AAAAGATCTCTGGTCCGCTT

2589 SEQ ID NO: 3258 1.7 -23.5 67.1 -25.2 0 -6.3 AGAATCTAAGGCAGATTTTT

2889 SEQ ID NO: 3259 1.7 -18.9 58.8 -18.4 -2.2 -6.6 TTTCATAGAAATCAGGTAGC

3188 SEQ ID NO: 3260 1.7 -19.2 60 -20.4 -0.1 -4.4 TCTACATCCTAGAATTTTGG

3221 SEQ ID NO: 3261 1.7 -20.3 61.8 -21.5 -0.1 -3.8 TAAGAATACATATATGAAGT

3477 SEQ ID NO: 3262 1.7 -14 47.7 -15.2 0 -8.2 AGCTCCGAAGCCCATAAGCG

99 SEQ ID NO: 3263 1.8 -27.9 72.8 -27.9 -1.8 -7.3 AGCAAAGCATCCTTGTTCAA

501 SEQ ID NO: 3264 1.8 -22.7 66 -23.6 -0.7 -4.6 ACCATCGAATAAGCAAAGCA

512 SEQ ID NO: 3265 1.8 -20.6 59.1 -21.5 -0.7 -5.9 TGCTGGTGACTTCCACCCCA

736 SEQ ID NO: 3266 1.8 -30.9 82.2 -29.7 -3 -9.2 GTGAAACAAATTACTGCAAG

821 SEQ ID NO: 3267 1.8 -16.6 52.2 -17.9 -0.1 -5.1 ACAGTTCCTCAAACGACCCT

1867 SEQ ID NO: 3268 1.8 -25.9 70.4 -26.3 -1.3 -3.8 GCTTTAAAGAAATGCTTGCC

3103 SEQ ID NO: 3269 1.8 -21 61.3 -22.1 -0.5 -8.1 GAAATCAGGTAGCATTATAA

3181 SEQ ID NO: 3270 1.8 -17.7 55.6 -19.5 0 -4.1 CATCATCATAGAAATACACC

259 SEQ ID NO: 3271 1.9 -18.6 56.8 -20.5 0 -2.9 AGTGCTGAGCCTATGCACTC

404 SEQ ID NO: 3272 1.9 -26.9 77.9 -25.5 -3.3 -9.1 CAGTGCTGAGCCTATGCACT

405 SEQ ID NO: 3273 1.9 -27.2 77.2 -25.8 -3.3 -9.1 TCATGCTGGTGACTTCCACC

739 SEQ ID NO: 3274 1.9 -27.3 77 -26.6 -2.6 -9.6 GCAGCACCCGGCAGTGCACT

1398 SEQ ID NO: 3275 1.9 -32.5 85.5 -30.8 -3.6 -13.3 CCTGCGGTCCAGTCTCCAGG

1427 SEQ ID NO: 3276 1.9 -31.8 86.2 -32.8 -0.7 -5.7 CCCTGTGTGTAACCAGCCGT

1611 SEQ ID NO: 3277 1.9 -30.2 79.9 -30.6 -1.4 -6.4 GTACCACAATTGCAATGAGA

1801 SEQ ID NO: 3278 1.9 -21.1 61.8 -22.2 0 -9.3 CAGCAAGTAGCAGACATCTC

2470 . ■ SEQ ID NO: 3279 1.9 -23.1 69.3 -23.4 -1.6 -5.2 TCAGAAGGGTTCTGTGAATG

2639 SEQ ID NO: 3280 1.9 -21.1 64.1 -20.4 -2.6 -7.9 TAGACAGTTATTCAGGCGTC

2965 SEQ ID NO: 3281 1.9 -22.8 68.9 -24.7 0 -4.1 TAAAGTGAACTGCTGTTAAT

3304 SEQ ID NO: 3282 1.9 -17.5 54.9 -18.5 -0.7 -7.7

192 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

TACAAATGACAGCTCAATTC 3349 SEQ ID NO: 3283 1.9 -18.3 56.6 -19.6 -0.3 -4.4

AGGGTATCATAAAGTGGAAC 536 SEQ ID NO: 3284 2 -19.2 59.1 -21.2 0 -2.9

TTGACTATGTACGTGATGGC 566 SEQ ID NO: 3285 2 -22.2 65.6 -24.2 0 -5.2

GCTTGTCAACAAAAACCAGA 601 SEQ ID NO: 3286 2 -20 58.6 -22 0 -5.4

CTGTGTGTAACCAGCCGTCT 1609 SEQ ID NO:3287 2 -27.5 76.7 -28.5 -0.9 -5.8

AAGTTAATCCCAACATGATC

3055 SEQ ID NO: 3288 2 -19.9 59.3 -21.2 -0.5 -5.2 CACATTTCATAGAAATCAGG

3192 SEQ ID NO: 3289 2 -18.1 56.4 -18.8 -1.2 -6.1

TTCGTGCACCACCACTACCC 208 SEQ ID NO: 3290 2.1 -29.8 78.2 -31.1 -0.6 -8.4

GCCTTCTCTGGCTTGTCAAC 611 SEQ ID NO: 3291 2.1 -27.2 78.6 -27.7 -1.5 -6.1

CACTTGTGAAACAAATTACT 826 SEQ ID NO: 3292 2.1 -16.7 52.6 -16.9 -1.9 -5.4

GTCATCCATGAGCAGCCTGA 1056 SEQ ID NO: 3293 2.1 -27.8 78.5 -29.4 -0.1 -5.3

TCATAGAAATCAGGTAGCAT 3186 SEQ ID NO: 3294 2.1 -19.7 60.6 -21.8 0 -4.1

CCAGGAAATGAACTTTCCAG 3244 SEQ ID NO: 3295 2.1 -21.4 61.6 -19.7 -3.8 -8.2

AGCTCAATTCAGTCAAATGT

3339 SEQ ID NO: 3296 2.1 -20.4 62.3 -22.5 0 -4.3 ATGACAGCTCAATTCAGTCA

3344 SEQ ID NO: 3297 2.1 -22.1 66.7 -22.9 -1.2 -6.4

TCCGAGAGCCTAAACAAGGG 331 SEQ ID NO:3298 2.2 -24 66.1 -24.8 -1.3 -6.6

TTTCCGAGAGCCTAAACAAG 333 SEQ ID NO: 3299 2.2 -21.8 62.1 -24 0 -3.2

ACAGTGGGTTGAAGCACCTT 1079 SEQ ID NO:3300 2.2 -25.4 72.8 -26.6 -0.9 -5.2

GGTACCACAATTGCAATGAG 1802 SEQ ID NO: 3301 2.2 -21.7 63 -23.1 0 -9.3

CAGTTCCTCAAACGACCCTT 1866 SEQ ID NO: 3302 2.2 -25.8 70.2 -26.6 -1.3 -3.8

CAGCTCAATTCAGTCAAATG

3340 SEQ ID NO: 3303 2.2 -19.9 60.5 -22.1 0 -4.4 CGTACCAGAAGGTGGTGAGT

127 SEQ ID NO:3304 2.3 -25.1 71.8 -25.3 -2.1 -7.7

CGTGGCGTACCAGAAGGTGG 132 SEQ ID NO: 3305 2.3 -27.1 73.6 -27.8 -1.6 -7.4

TCTGGCTTGTCAACAAAAAC 605 SEQ ID NO: 3306 2.3 -19.2 57.8 -20.6 -0.8 -5.4

TTCATGCTGGTGACTTCCAC 740 SEQ ID NO: 3307 2.3 -25.4 73.8 -26.7 -0.9 -6.8

CTGCTCTGAGGAACGTCAGC 1339 SEQ ID NO:3308 2.3 -25.7 73.5 -27.3 -0.5 -6.5

GGAGACAGAAGATTTAAAAC 2411 SEQ ID NO: 3309 2.3 -15.8 51.1 -18.1 0 -5

CTCAGAGATAGCAAAGTCCT 2453 SEQ ID NO: 3310 2.3 -22.5 66.7 -24.8 0 -4.1

GAAACCTTATGCTCCAACAG 2707 SEQ ID NO: 3311 2.3 -22.1 63.1 -24.4 0 -3.6

CAAGTTAATCCCAACATGAT

3056 SEQ ID NO:3312 2.3 -20.2 59.2 -21.8 -0.5 -5.2 CTCAAGTATATACTCCCTTA

3126 SEQ ID NO : 3313 2.3 -21.8 65 -23.3 0 -9.2

193 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo ACGATCACCATCGAATAAGC

518 SEQ ID NO: 3314 2.4 -21.5 61.1 -21.4 -2.5 -7.5 TTCTCTGGCTTGTCAACAAA

608 SEQ ID NO: 3315 2.4 -21.8 64.9 -23.4 -0.6 -5.4 GGTCATCCATGAGCAGCCTG

1057 SEQ ID NO: 3316 2.4 -28.4 79.8 -30.8 4.5 -5.3 GATGATGCCGCTGCGAAGCT

1212 SEQ ID NO: 3317 2.4 -27.7 73.5 -27.1 -3 -10.2 AACCATTTTCCAATGTCCCC

1628 SEQ ID NO: 3318 2.4 -26.5 71.5 -27.7 -1.1 -3.6 CTTGTATATAATACATGTAC

3401 SEQ ID NO:3319 2.4 -16.3 53.3 -17.1 -1.5 -8.2 CTGTTTATATGAAAGCCATT

369 SEQ ID NO: 3320 2.5 -19.5 59 -21.5 -0.1 -3.6 CCTGTTTATATGAAAGCCAT

370 SEQ ID NO: 3321 2.5 -21.4 62.4 -23.9 0 -3.2 AGCCCTTCTGGATCAGTGCT

418 SEQ ID NO: 3322 2.5 -28.9 82.1 -30.8 -0.3 -5.3 AGAAAGATATCAAAGTATCA

952 SEQ ID NO:3323 2.5 -15.2 50.3 -16.9 -0.6 -6.1 AAGAAAGATATCAAAGTATC

953 SEQ ID NO:3324 2.5 -13.8 47.4 -15.7 -0.3 -6.9 TGATGATGCCGCTGCGAAGC

1213 SEQ ID NO: 3325 2.5 -26.8 71.6 -27.1 -2.2 -9.6 GATAGCAAAGTCCTAACCCC

2447 SEQ ID NO: 3326 2.5 -25.1 69 -27.6 0 -4.1 CTGAGCATGGCTGATCCAGG

2941 SEQ ID NO: 3327 2.5 -26.8 75.6 -28 -1.2 -6.3 AAAGTGAACTGCTGTTAATT

3303 SEQ ID NO: 3328 2.5 -17.9 55.8 -19.5 -0.7 -7.7 ACAGCTCAATTCAGTCAAAT

3341 SEQ ID NO:3329 2.5 -20.1 61.1 -22.6 0 -4.4 AAAATACCGGAACAGCTCAT

24 SEQ ID NO: 3330 2.6 -20.4 58.6 -23 0 -7.1 CCAGAAGGTGGTGAGTGCTG

123 SEQ ID NO:3331 2.6 -25.9 74.5 -27.8 -0.5 -4.6 TCGTGCACCACCACTACCCG

207 SEQ ID NO: 3332 2.6 -30.5 77.6 -32.3 -0.6 -8.4 GATCTTCGTGCACCACCACT

212 SEQ ID NO: 3333 2.6 -27.8 76.2 -29.6 -0.6 -8.4 AAGATGCCAATGAACTGATC

452 SEQ ID NO: 3334 2.6 -19.7 58.6 -22.3 0 -3.9 ATGATGCCGCTGCGAAGCTC

1211 SEQ ID NO: 3335 2.6 -27.5 73.8 -27.1 -3 -9.5 CCTGTGTGTAACCAGCCGTC

1610 SEQ ID NO: 3336 2.6 -28.6 78.3 -29.7 -1.4 -6.4 AGCATGGCTGATCCAGGTAA

2938 SEQ ID NO: 3337 2.6 -25.5 72.8 -26.6 -1.4 -6.9 AAAATCTGTTGGCCTTTACA

3013 SEQ ID NO: 3338 2.6 -21.2 62.4 -23.8 0 -7.2 ATTTCATAGAAATCAGGTAG

3189 SEQ ID NO: 3339 2.6 -17.4 55.8 -18.9 -1 -5.9 ATTAACTTTAAAAAATCCCT

3277 SEQ ID NO: 3340 2.6 -15.9 50.4 -18.5 0 -4.3 TGACAGCTCAATTCAGTCAA

3343 SEQ ID NO: 3341 2.6 -21.4 64.5 -22.9 -1 -5.9 GAATACATATATGAAGTTAG

3474 SEQ ID NO: 3342 2.6 -14.8 49.7 -17.4 0 -7.3 CCCCTGTGTGTAACCAGCCG

1612 SEQ ID NO: 3343 2.7 -31 79.9 -32.2 -1.4 -4.8 TAACCATTTTCCAATGTCCC

1629 SEQ ID NO: 3344 2.7 -24.2 67.6 -25.7 -1.1 -3.6

194 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

>sition oligo binding ation Duplex ture oligo oligo GCAGAATTTGCAGCAAGTAG

2480 SEQ ID NO: 3345 2.7 -21.8 64.9 -22.7 -1.8 -8.5 TCTTCACTATAGAATCTAAG

2899 SEQ ID NO: 3346 2.7 -17.2 55.6 -19.9 0 -6 CAACATGATCTTTTGATATG

3045 SEQ ID NO: 3347 2.7 -17.4 55 -18.8 -1.2 -6.1 TAAAGAAATGCTTGCCTGAG

3099 SEQ ID NO: 3348 2.7 -19.6 58.2 -21.7 -0.3 -3.9 TCAGTGCTGAGCCTATGCAC

406 SEQ ID NO: 3349 2.8 -26.7 77 -27 -2.5 -10 TCCAAGGGTATCATAAAGTG

540 SEQ ID NO: 3350 2.8 -20.3 61.1 -23.1 0 -3.6 TCTCAGAGATAGCAAAGTCC

2454 SEQ ID NO: 3351 2.8 -22 66.3 -24.8 0 -6.3 GCAAGTTAATCCCAACATGA

3057 SEQ ID NO: 3352 2.8 -22 63 -24.1 -0.5 -5.2 AATGACAGCTCAATTCAGTC

3345 SEQ ID NO:3353 2.8 -20.7 63.2 -22.9 -0.3 -4.6 ACATGTACTCTCACAGACCC

3389 SEQ ID NO: 3354 2.8 -25 72.1 -27.8 0 -7 TTAAGAATACATATATGAAG

3478 SEQ ID NO: 3355 2.8 -12.9 45.4 -15.2 0 -8.2 CGAAGCCCATAAGCGTGTTG

94 SEQ ID NO: 3356 2.9 -25.3 68.3 -27.3 -0.7 -4.1 CTCCGAAGCCCATAAGCGTG

97 SEQ ID NO: 3357 2.9 -27.3 71.6 -29.3 -0.7 -4.1 CTGGATCAGTGCTGAGCCTA

411 SEQ ID NO: 3358 2.9 -26.7 76.8 -29 2.3 -9.1 TTGAAGCACCTTGAGGTCAT

1071 SEQ ID NO: 3359 2.9 -23.8 69.2 -26.2 -0.2 -7.5 TGATGCCGCTGCGAAGCTCT

1210 SEQ ID NO: 3360 2.9 -28.4 75.6 -28.3 -3 -10.2 GAGGAACGTCAGCACAGTGG

1332 SEQ ID NO: 3361 2.9 -24.8 71 -27.7 0 -6 TCTGCGACCTGAAATAGTTC

2059 SEQ ID NO:3362 2.9 -22.2 64.6 -24.6 -0.1 -5.2 GAATTTGCAGCAAGTAGCAG

2477 SEQ ID NO: 3363 2.9 -21.8 64.9 -23.1 -1.6 -8.5 CGAATCAGAAGGGTTCTGTG

2643 SEQ ID NO: 3364 2.9 -21.9 64.5 -22.8 -2 -7.3 TCGTAACCCTTACGAATCAG

2655 SEQ ID NO: 3365 2.9 -22.3 62.9 -21.9 -3.3 -8.9 CACAGCTGAGCATGGCTGAT

2946 SEQ ID NO: 3366 2.9 -25.9 73.7 -25.6 -3.2 -9.9 GGCAAGTTAATCCCAACATG

3058 SEQ ID NO: 3367 2.9 -22.6 64.2 -25.5 0.2 -4.7 ATTAAGAATACATATATGAA

3479 SEQ ID NO: 3368 2.9 -12.9 45.3 -15.2 0 -8.5 AATTAAGAATACATATATGA

3480 SEQ ID NO: 3369 2.9 -12.9 45.3 -15.2 0 -8.5 AATGAACTGATCTGGGGCAG

444 SEQ ID NO: 3370 3 -22.3 64.9 -24.7 -0.3 -4.9 TGGAACGATCACCATCGAAT

522 SEQ ID NO: 3371 3 -21.8 61.1 -23.2 -1.6 -6.7 TACCACAATTGCAATGAGAA

1800 SEQ ID NO: 3372 3 -19.2 57.1 -21.4 0 -9.3 CTGATGATGCCGCTGCGAAG

1214 SEQ ID NO: 3373 3.1 -25.9 69.5 -27.6 -1.3 -9.6 GCTGCTCTGAGGAACGTCAG

1340 SEQ ID NO: 3374 3.1 -25.7 73.5 -27.8 -0.9 -6.5 ATCAGGCCTGGAGAACCGAG

2837 SEQ ID NO:3375 3.1 -26.3 71.9 -27.3 -1.2 -12.2

195 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular

Dsition oligo binding ation Duplex ture oligo oligo GGAATCAGGCCTGGAGAACC

2840 SEQ ID NO: 3376 3.1 -26 71.9 -27.4 -0.1 -11.6 CATTTCATAGAAATCAGGTA

3190 SEQ ID NO: 3377 3.1 -18.1 57 -19.9 -1.2 -6.1 AATTAACTTTAAAAAATCCC

3278 SEQ ID NO: 3378 3.1 -14.3 47.3 -17.4 0 -4.3 GCAATTAAGAATACATATAT

3482 SEQ ID NO: 3379 3.1 -14.8 49.1 -17.9 0 -3.4 GGCGTACCAGAAGGTGGTGA

129 SEQ ID NO: 3380 3.2 -26.9 75 -28.2 -1.8 -11.2 CAGCACCCGGCAGTGCACTC

1397 SEQ ID NO: 3381 3.2 -31.1 83 -30.7 -3.6 -13.3 GGTAACCATTTTCCAATGTC

1631 SEQ ID NO: 3382 3.2 -22.6 66 -24.6 -1.1 -5.1 GACCAGAATCCTTCCCAAGT

1933 SEQ ID NO: 3383 3.2 -26.4 72.4 -29.6 0.3 -2.5 AATAGTTCCGCAGCTCTGGC

2047 SEQ ID NO: 3384 3.2 -27 76.2 -29.5 -0.5 -5 AGCAGACAGCTGCAGAATTT

2491 SEQ ID NO: 3385 3.2 -23.3 68.4 -22.2 -4.3 -11 TTAACTTTAAAAAATCCCTG

3276 SEQ ID NO: 3386 3.2 -15.9 50.4 -19.1 0 -4.1 CATGTACTCTCACAGACCCC

3388 SEQ ID NO: 3387 3.2 -26.8 75.1 -30 0 -4.8 GGAACGATCACCATCGAATA

521 SEQ ID NO: 3388 3.3 -21.5 60.7 -22.3 -2.5 -6.5 GGGTTGAAGCACCTTGAGGT

1074 SEQ ID NO: 3389 3.3 -26.3 75.1 -28.6 -0.9 -7.6 TCCCCTGTGTGTAACCAGCC

1613 SEQ ID NO: 3390 3.3 -30.6 82 -32.4 -1.4 -3.8 AATGTCCCCTGTGTGTAACC

1617 SEQ ID NO: 3391 3.3 -26.6 73.8 -29.4 -0.1 -2.1 CAGGGAGACAGAAGATTTAA

2414 SEQ ID NO: 3392 3.3 -18.9 58 -22.2 0 -2.2 AAAAAGATCTCTGGTCCGCT

2590 SEQ ID NO: 3393 3.3 -22.7 64.7 -26 0 -6.3 AAGGGTTCTGTGAATGCCTG

2635 SEQ ID NO: 3394 3.3 -24.1 69.6 -26.6 -0.6 -4.8 ATCAGAAGGGTTCTGTGAAT

2640 SEQ ID NO:3395 3.3 -21.1 64.2 -21.8 -2.6 -7.9 GGCCTGGAGAACCGAGTCCA

2833 SEQ ID NO: 3396 3.3 -29.5 78.2 -31.7 -1 -8.6 TTGTCTTCACTATAGAATCT

2902 SEQ ID NO: 3397 3.3 -19.5 61.5 -22.8 0 -6 ACTTTTTGTGCAATTAAGAA

3491 SEQ ID NO: 3398 3.3 -17.5 55.1 -20.3 0 -7.8 GAGCAAAGATGCCAATGAAC

457 SEQ ID NO: 3399 3.4 -20.2 58.9 -21.4 -2.2 -6.4 ACCATTTTCCAATGTCCCCT

1627 SEQ ID NO: 3400 3.4 -28.1 75.5 -30.3 -1.1 -3.6 AGATAGCAAAGTCCTAACCC

2448 SEQ ID NO: 3401 3.4 -23.1 65.8 -26.5 0 -3.3 TTAGAGCAGCAGACAGCTGC

2498 SEQ ID NO: 3402 3.4 -25.4 74.6 -24.1 -4.7 -12.7 GGGACTGGAGAAGAACATGA

2678 SEQ ID NO: 3403 3.4 -21.2 62.3 -24.6 0 -5.2 CGGAACAGCTCATGGGCTTG

17 SEQ ID NO: 3404 3.5 -25.8 71.6 -27.5 -1.6 -11 ACTTGTGAAACAAATTACTG

825 SEQ ID NO: 3405 3.5 -16 51.4 -17.6 -1.9 -5.4 AGCACAGTGGCAGACACCGG

1322 SEQ ID NO: 3406 3.5 -28 76.5 -29.9 -1.6 -7.4

196 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

CCGGAACAGCTCATGGGCTT 18 SEQ ID NO: 3407 3.6 -27.8 75.2 -29.6 -1.6 -11

GGTATCATAAAGTGGAACGA 534 SEQ ID NO:3408 3.6 -19.4 58.3 -22 -0.9 -3.8

GGGAGACAGAAGATTTAAAA 2412 SEQ ID NO:3409 3.6 -16.8 53 -20.4 0 -5

CAGCAGACAGCTGCAGAATT 2492 SEQ ID NO: 3410 3.6 -23.9 69.2 -23.2 -4.3 -10.8

TAGAATCTAAGGCAGATTTT 2890 SEQ ID NO:3411 3.6 -18.5 57.9 -19.9 -2.2 -6.6

CCTCTGGAAACCTTCGTATA 288 SEQ ID NO:3412 3.7 -23.6 66.6 -26.4 -0.8 -3.5

CACCATCGAATAAGCAAAGC 513 SEQ ID NO: 3413 3.7 -20.6 59.1 -24.3 0 -4.7

AAAAGCTGAACAATCGCTCA

894 SEQ ID NO: 3414 3.7 -19.7 57.7 -21.3 -2.1 -5.6 TAACCCTTACGAATCAGAAG

2652 SEQ ID NO:3415 3.7 -19.8 57.9 -23.5 0 -3.5

GAAACCACAGGGGACTGGAG

2688 SEQ ID NO:3416 3.7 -24.1 67.6 -25.1 -2.7 -6.9 AGAAACCACAGGGGACTGGA

2689 SEQ ID NO: 3417 3.7 -24.1 67.6 -25.1 -2.7 -6.4 GACAGTTATTCAGGCGTCAC

2963 SEQ ID NO: 3418 3.7 -24 71 -27.7 0 -5.1

GACAGCTCAATTCAGTCAAA 3342 SEQ ID NO:3419 3.7 -20.7 62.4 -23.8 -0.3 -4.7

TTGTATATAATACATGTACT 3400 SEQ ID NO:3420 3.7 -16.3 53.3 -18.4 -1.5 -8.6

GTGGCGTACCAGAAGGTGGT 131 SEQ ID NO: 3421 3.8 -27.5 77.1 -29.3 -1.9 -11.2

GAACGATCACCATCGAATAA 520 SEQ ID NO:3422 3.8 -19.6 56.8 -20.9 -2.5 -6.5

CAAAAGCTGAACAATCGCTC

895 SEQ ID NO:3423 3.8 -19.7 57.7 -21.4 -2.1 -5.6 GAGATTGTGGAACTGTGCCA

2136 SEQ ID NO:3424 3.8 -24.4 70.2 -27.5 -0.5 -4.4

TACTGGAAACCTTATGCTCC 2712 SEQ ID NO:3425 3.8 -23.2 66.3 -27 0 -3.6

CTTCACTATAGAATCTAAGG 2898 SEQ ID NO:3426 3.8 -18 56.9 -21.8 0 -5.6

CTTTTTGTGCAATTAAGAAT 3490 SEQ ID NO: 3427 3.8 -17.3 54.6 -21.1 0 -6.3

GGCAGCACCCGGCAGTGCAC 1399 SEQ ID NO: 3428 3.9 -32.8 86.1 -33.1 -3.6 -13.3

AGACCAGAATCCTTCCCAAG 1934 SEQ ID NO:3429 3.9 -25.2 69.6 -28.6 -0.1 -2.8

AAGTAGACAGTTATTCAGGC 2968 SEQ ID NO:3430 3.9 -20.9 64.9 -24.8 0 -2.9

GGAACAGCTCATGGGCTTGC 16 SEQ ID NO: 3431 4 -26.8 76 -29.2 -1.4 -10.8

CAAAAGCTCCGAAGCCCATA 103 SEQ ID NO:3432 4 -24.6 65.8 -27.5 -1 -5

AGCAAGTAGCAGACATCTCA 2469 SEQ ID NO:3433 4 -23.1 69.3 -25.5 -1.6 -5.2

GGGATTTAAAAAGATCTCTG 2597 SEQ ID NO:3434 4 -17.3 54.5 -20.8 -0.2 -6.3

CCTTACGAATCAGAAGGGTT 2648 SEQ ID NO:3435 4 -22.3 64.2 -25.4 -0.7 -5.8

GGCAGATTTTTAAATAACCC 2880 SEQ ID NO:3436 4 -20.2 59.5 -24.2 0.3 -4.5

GTACTCTCACAGACCCCAAA 3385 SEQ ID NO:3437 4 -25.4 70.6 -29.4 0 -4

197 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo ATGTACTCTCACAGACCCCA

3387 SEQ ID NO: 3438 4 -26.8 75.1 -30.8 0 -4.8 AAGCTCCGAAGCCCATAAGC

100 SEQ ID NO: 3439 4.1 -26.4 70.7 -28.7 -1.8 -6 TCACCATCGAATAAGCAAAG

514 SEQ ID NO: 3440 4.1 -19.2 56.7 -23.3 0 -5.2 GACAGTGGGTTGAAGCACCT

1080 SEQ ID NO: 3441 4.1 -25.9 73.8 -29 -0.9 -5.2 AGGGAGACAGAAGATTTAAA

2413 SEQ ID NO: 3442 4.1 -17.5 54.9 -21.6 0 -4.6 AAACCACAGGGGACTGGAGA

2687 SEQ ID NO: 3443 4.1 -24.1 67.6 -25.5 -2.7 -6.9 CAGGCCTGGAGAACCGAGTC

2835 SEQ ID NO: 3444 4.2 -27.5 75.2 -30 -1.2 -11.2 ACTCTCACAGACCCCAAAAC

3383 SEQ ID NO: 3445 4.2 -24 66.5 -28.2 0 -2.4 TTTTTGTGCAATTAAGAATA

3489 SEQ ID NO: 3446 4.2 -16.1 52.2 -20.3 0 -5.6 AAGGTGGTGAGTGCTGCAAA

119 SEQ ID NO: 3447 4.3 -23.7 68.7 -27.5 0 -7.8 AGAAGGTGGTGAGTGCTGCA

121 SEQ ID NO: 3448 4.3 -25.7 75.3 -29.5 0 -7.6 CAGAAGGTGGTGAGTGCTGC

122 SEQ ID NO: 3449 4.3 -25.7 75.3 -30 0 -5 CTGTATTCCCCTCTGGAAAC

297 SEQ ID NO: 3450 4.3 -25.1 70.3 -27.8 -1.5 -5.6 CAACCTGTTTATATGAAAGC

373 SEQ ID NO: 3451 4.3 -18.9 57.4 -23.2 0 -3.2 AAGGGTATCATAAAGTGGAA

537 SEQ ID NO: 3452 4.3 -18.3 56.6 -22.6 0 -2.9 GAAGCACCTTGAGGTCATCC

1069 SEQ ID NO: 3453 4.3 -26.1 74.3 -29.9 -0.1 -7.3 AGAGATTGTGGAACTGTGCC

2137 SEQ ID NO: 3454 4.3 -23.7 69.3 -27.3 -0.5 -4 GAATCAGAAGGGTTCTGTGA

2642 SEQ ID NO: 3455 4.3 -21.7 65.5 -23.4 -2.6 -7.9 TTACTGGAAACCTTATGCTC

2713 SEQ ID NO: 3456 4.3 -21.3 63 -25.6 0 -3.6 TGAAGCACCTTGAGGTCATC

1070 SEQ ID NO: 3457 4.4 -24.1 70.5 -28 -0.2 -7.5 GGGAAGACAGTGGGTTGAAG

1085 SEQ ID NO: 3458 4.4 -22.6 66.6 -27 0 -4.6 TTCACTATAGAATCTAAGGC

2897 SEQ ID NO: 3459 4.4 -18.9 59.1 -23.3 0 -6 AACGATCACCATCGAATAAG

519 SEQ ID NO: 3460 4.5 -19 55.8 -21 -2.5 -6.5 AACTGTGCCATTTCCTCTGA

2126 SEQ ID NO: 3461 4.5 -25.5 72.6 -30 0 -3.3 CACTATAGAATCTAAGGCAG

2895 SEQ ID NO: 3462 4.5 -19.1 58.8 -23.6 0 -6 AGCTGAGCATGGCTGATCCA

2943 SEQ ID NO: 3463 4.5 -27.4 77.3 -30.2 -1.7 -7.1 TGTACTCTCACAGACCCCAA

3386 SEQ ID NO: 3464 4.5 -26.1 72.7 -30.6 0 -4.8 GAAATATTTATTTTGGTTTC

3607 SEQ ID NO: 3465 4.5 -16.1 53 -20 -0.3 -6.7 ACCAGAAGGTGGTGAGTGCT

124 SEQ ID NO: 3466 4.6 -26.1 75.3 -28.9 -1.8 -7.2 GGATCTTCGTGCACCACCAC

213 SEQ ID NO: 3467 4.6 -28.1 76.8 -32 -0.4 -8.4 GCATGGTTAGGCAGCACCCG

1408 SEQ ID NO: 3468 4.6 -29.9 80.1 -33.8 -0.5 -5.8

198 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

AACCACAGGGGACTGGAGAA 2686 SEQ ID NO:3469 4.6 -24.1 67.6 -26.9 -1.8 -6.9

AGGCCTGGAGAACCGAGTCC 2834 SEQ ID NO:3470 4.6 -28.8 77.6 -32.1 -1.2 -9.2

TACTCTCACAGACCCCAAAA 3384 SEQ ID NO: 3471 4.6 -23.5 65.5 -28.1 0 -2.4

GCGTACCAGAAGGTGGTGAG 128 SEQ ID NO: 3472 4.7 -25.7 72.8 -28.3 -2.1 -11.2

ATCAGTGCTGAGCCTATGCA 407 SEQ ID NO: 3473 4.7 -26.5 76.3 -29.6 -1.4 -10.9

GATGCCGCTGCGAAGCTCTG 1209 SEQ ID NO:3474 4.7 -28.4 75.6 -30.1 -3 -10.2

AGCTGCAGAATTTGCAGCAA

2484 SEQ ID NO: 3475 4.7 -23.6 68 -20.7 -7.6 -18.4 ACTGGAAACCTTATGCTCCA

2711 SEQ ID NO:3476 4.7 -24.2 67.9 -28 -0.8 -4.2

TCCGAAGCCCATAAGCGTGT 96 SEQ ID NO:3477 4.8 -27.6 72.8 -31.5 -0.7 -4.1

GCAACCTGTTTATATGAAAG 374 SEQ ID NO: 3478 4.8 -18.9 57.4 -23.7 0 -3.4

AATCAGAAGGGTTCTGTGAA 2641 SEQ ID NO: 3479 4.8 -20.4 62 -22.6 -2.6 -7.9

GTTGACTATGTACGTGATGG 567 SEQ ID NO: 3480 4.9 -21.6 64.6 -26.5 0 -5.2

CTGCAGAATTTGCAGCAAGT 2482 SEQ ID NO:3481 4.9 -23 67.1 -24.2 -3.7 -11.5

GGAAACCTTATGCTCCAACA

2708 SEQ ID NO:3482 4.9 -23.3 65.3 -27.7 -0.1 -3.6 TGGAAACCTTATGCTCCAAC

2709 SEQ ID NO: 3483 4.9 -22.6 64.1 -26.6 -0.8 -4.2 TGGTGAGTGCTGCAAAAGCT

115 SEQ ID NO: 3484 5 -24 69 -26.9 -2.1 -7.8

CAGCTGCAGAATTTGCAGCA

2485 SEQ ID NO:3485 5 -25 71.5 -22.4 -7.6 -18.4 TAACTTTAAAAAATCCCTGG

3275 SEQ ID NO:3486 5 -17 52.3 -22 0 -4.3

AGAAATATTTATTTTGGTTT 3608 SEQ ID NO:3487 5 -15.7 51.9 -20.1 -0.3 -6.7

AACCTGTTTATATGAAAGCC 372 SEQ ID NO:3488 5.1 -20.2 59.8 -25.3 0 -3.2

CCAAGGGTATCATAAAGTGG 539 SEQ ID NO: 3489 5.1 -21.1 62.2 -26.2 0 -3.1

CATGGTTAGGCAGCACCCGG 1407 SEQ ID NO:3490 5.1 -29.3 78.4 -33.7 -0.5 -5.8

TCAGGCCTGGAGAACCGAGT 2836 SEQ ID NO:3491 5.1 -27.5 75.2 -30.5 -1.2 -12.2

AATCAGGCCTGGAGAACCGA 2838 SEQ ID NO: 3492 5.1 -25.6 69.5 -28.6 -1.2 -12.2

CAGCTGAGCATGGCTGATCC 2944 SEQ ID NO:3493 5.1 -27.4 77.3 -30.2 -2.3 -9.3

GTGAGTGCTGCAAAAGCTCC 113 SEQ ID NO: 3494 5.2 -25.2 71.8 -28.3 -2.1 -8.2

GAAGGTGGTGAGTGCTGCAA 120 SEQ ID NO:3495 5.2 -25 72.4 -29.7 0 -7.8

CCTTCTGGATCAGTGCTGAG 415 SEQ ID NO: 3496 5.2 -25.7 75 -29.6 -0.3 -10.5

CCACAGGGGACTGGAGAAGA 2684 SEQ ID NO:3497 5.2 -25.2 70.7 -27.7 -2.7 -5.8

AGAATACATATATGAAGTTA 3475 SEQ ID NO:3498 5.2 -14.8 49.7 -19.5 0 -8.2

AAATACCGGAACAGCTCATG 23 SEQ ID NO: 3499 5.3 -21.1 60.4 -26.4 0 -6.2

199 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GGTGACTTCCACCCCACACC

732 SEQ ID NO:3500 5.3 -31.3 82 -34.3 -2.3 -7.3 AAATGACAGCTCAATTCAGT

3346 SEQ ID NO: 3501 5.3 -19.6 59.7 -24.3 -0.3 -4.4

CTCTGGAAACCTTCGTATAA 287 SEQ ID NO: 3502 5.4 -20.9 61.1 -26.3 0 -3.3

TTATATGAAAGCCATTCATA 365 SEQ ID NO:3503 5.4 -18.1 56 -20.5 -3 -9.4

AGTGGAACGATCACCATCGA 524 SEQ ID NO: 3504 5.4 -23.7 66.1 -26.6 -2.5 -7.5

GGGGAAGACAGTGGGTTGAA 1086 SEQ ID NO:3505 5.4 -23.8 68.9 -29.2 0 -4.6

TACATGTACTCTCACAGACC 3390 SEQ ID NO:3506 5.4 -22.7 67.7 -27.5 0 -8.6

TTTTGTGCAATTAAGAATAC 3488 SEQ ID NO:3507 5.4 -16.2 52.4 -21.6 0 -5.6

TGGCGTACCAGAAGGTGGTG 130 SEQ ID NO:3508 5.5 -26.3 73.5 -29.7 -2.1 -11.2

GCAAGTAGCAGACATCTCAG 2468 SEQ ID NO: 3509 5.5 -23.1 69.3 -27.6 -0.9 -4.5

AGACAGTTATTCAGGCGTCA 2964 SEQ ID NO: 3510 5.5 -23.8 70.7 -28.4 -0.8 -5.1

GTTTCCGAGAGCCTAAACAA 334 SEQ ID NO:3511 5.6 -23 64.8 -27.8 -0.6 -5.6

GATCAGTGCTGAGCCTATGC

408 SEQ ID NO: 3512 5.6 -26.4 76.6 -31.1 -0.3 -9.4 GTGGAACGATCACCATCGAA

523 SEQ ID NO: 3513 5.6 -23 63.9 -26.1 -2.5 -7

TTTGTTGACTATGTACGTGA

570 SEQ ID NO: 3514 5.6 -20.6 62.7 -26.2 0 -5.2

TGGTGACTTCCACCCCACAC

733 SEQ ID NO:3515 5.6 -29.3 78.5 -31.9 -3 -7.5 AAGACAGTGGGTTGAAGCAC

1082 SEQ ID NO: 3516 5.6 -22.3 66.1 -27.2 -0.5 -4.6

TAAAAAGATCTCTGGTCCGC

2591 SEQ ID NO: 3517 5.6 -21.5 62.4 -27.1 0 -5.8 CCGAAGCCCATAAGCGTGTT

95 SEQ ID NO:3518 5.7 -27.3 71.7 -33 0.1 -4.1

GGAAGACAGTGGGTTGAAGC 1084 SEQ ID NO:3519 5.7 -23.2 68.2 -28.9 0 -4.6

GAAACAAATTACTGCAAGAT 819 SEQ ID NO: 3520 5.8 -16 50.8 -21.3 -0.2 -4.9

GGGAATCAGGCCTGGAGAAC 2841 SEQ ID NO: 3521 5.8 -25.2 70.9 -29 0 -12.2

ACCGGAACAGCTCATGGGCT 19 SEQ ID NO: 3522 5.9 -27.9 75.4 -32.1 -1.5 -10.8

GCAGCAGACAGCTGCAGAAT 2493 SEQ ID NO:3523 5.9 -25.6 73.1 -25.7 -5.8 -13.1

TTAAAAAGATCTCTGGTCCG

2592 SEQ ID NO: 3524 5.9 -19.8 58.9 -25.7 0 -6.3 GGATCAGTGCTGAGCCTATG

409 SEQ ID NO: 3525 6 -25.8 74.7 -31.8 3 -8.3 CATTTTCCAATGTCCCCTGT

1625 SEQ ID NO:3526 6 -27.1 74.7 -32.3 -0.6 -3.1

AAAGTAGACAGTTATTCAGG 2969 SEQ ID NO:3527 6 -18.4 58.3 -24.4 0 -2.9

TTTGTGCAATTAAGAATACA 3487 SEQ ID NO:3528 6 -16.8 53.4 -22.8 0 -5.6

TCTGGAAACCTTCGTATAAT 286 SEQ ID NO:3529 6.1 -20 59.3 -25.2 -0.8 -3.5

ATCATAAAGTGGAACGATCA 531 SEQ ID NO:3530 6.1 -18.4 56 -23.5 -0.9 -5.3

200 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo

GCTGCAGAATTTGCAGCAAG 2483 SEQ ID NO:3531 6.1 -23.6 68 -22.9 -6.8 -17.7

TAGAGCAGCAGACAGCTGCA 2497 SEQ ID NO: 3532 6.1 -26 75.4 -25.5 -6.6 -13.8

TTGTTGACTATGTACGTGAT 569 SEQ ID NO: 3533 6.2 -20.5 62.3 -26.7 0 -5.2

GAATCAGGCCTGGAGAACCG 2839 SEQ ID NO: 3534 6.2 -25.6 69.5 -29.7 -1.2 -12.2

TTGTGCAATTAAGAATACAT 3486 SEQ ID NO:3535 6.2 -16.7 53.1 -22.9 0 -5.4

CTGGAAACCTTCGTATAATG 285 SEQ ID NO:3536 6.3 -19.6 58 -25 -0.8 -3.5

CAAATGACAGCTCAATTCAG 3347 SEQ ID NO:3537 6.3 -19.1 58 -24.8 -0.3 -4.4

GGTGAGTGCTGCAAAAGCTC 114 SEQ ID NO: 3538 6.4 -24.4 70.8 -28.7 -2.1 -7.9

TATATGAAAGCCATTCATAG 364 SEQ ID NO: 3539 6.4 -18 55.8 -21.2 -3.2 -9.7

GCTCCAACAGAAACCACAGG

2697 SEQ ID NO:3540 6.4 -24.2 66.9 -30.6 0 -3.6 TGCTCCAACAGAAACCACAG

2698 SEQ ID NO:3541 6.4 -23 64.5 -29.4 0 -3.6 CTTACTGGAAACCTTATGCT

2714 SEQ ID NO: 3542 6.4 -21.8 63.5 -28.2 0 -3.6

CATGGCTGATCCAGGTAACT

2936 SEQ ID NO:3543 6.4 -24.8 70.8 -29.5 -1.7 -5.8 ACAGCTGAGCATGGCTGATC

2945 SEQ ID NO:3544 6.4 -25.6 74.3 -28.8 -3.2 -9.9

GTACCAGAAGGTGGTGAGTG 126 SEQ ID NO:3545 6.5 -24.3 71.7 -28.7 -2.1 -5.7

AACCCTTACGAATCAGAAGG 2651 SEQ ID NO:3546 6.5 -21.3 60.7 -26.9 -0.8 -6

AGACAGTGGGTTGAAGCACC 1081 SEQ ID NO: 3547 6.6 -25 72.1 -31.1 -0.1 -4.7

GGGGACTGGAGAAGAACATG 2679 SEQ ID NO:3548 6.6 -21.8 63.5 -27.9 -0.2 -4.9

AATACCGGAACAGCTCATGG 22 SEQ ID NO:3549 6.7 -23 64.6 -29.7 0 -7.1

GTATCATAAAGTGGAACGAT 533 SEQ ID NO:3550 6.8 -18.2 55.9 -24 -0.9 -4

TGAAACAAATTACTGCAAGA 820 SEQ ID NO:3551 6.8 -16 50.8 -22.3 -0.2 -4.9

CCATTTTCCAATGTCCCCTG 1626 SEQ ID NO:3552 6.8 -27.9 74.8 -33.5 -1.1 -3.6

GAGATAGCAAAGTCCTAACC 2449 SEQ ID NO: 3553 6.8 -21.7 63.5 -28.5 0 -4.1

GCATGGCTGATCCAGGTAAC

2937 SEQ ID NO: 3554 6.8 -25.7 73.1 -31 -1.4 -6.9 AAGTGGAACGATCACCATCG

525 SEQ ID NO:3555 6.9 -22.4 62.9 -27.2 -2.1 -7.1

CCCTTACGAATCAGAAGGGT 2649 SEQ ID NO:3556 6.9 -24.2 67.4 -28.7 -2.4 -9.2

TATATAATACATGTACTCTC 3397 SEQ ID NO: 3557 6.9 -16.7 54.6 -23.1 0 -8.2

GGATTTAAAAAGATCTCTGG 2596 SEQ ID NO:3558 7 -17.3 54.5 -23.8 -0.2 -6.3

ACCACAGGGGACTGGAGAAG 2685 SEQ ID NO: 3559 7 -24.8 70 -29.1 -2.7 -6.9

AAGAATACATATATGAAGTT 3476 SEQ ID NO:3560 7 -14.4 48.5 -20.9 0 -8.2

TATCATAAAGTGGAACGATC 532 SEQ ID NO: 3561 7.1 -17.4 54.3 -23.5 -0.9 -4.9

201 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo binding ation Duplex ture oligo oligo TGTTGACTATGTACGTGATG

568 SEQ ID NO: 3562 7.1 -20.4 61.9 -27.5 0 -5.2 AACAGAAACCACAGGGGACT

2692 SEQ ID NO: 3563 7.2 -22.5 63.7 -28.9 -0.6 -3.9 CTGGAAACCTTATGCTCCAA

2710 SEQ ID NO: 3564 7.2 -23.3 65.3 -29.5 -0.9 -4.3 GTATATAATACATGTACTCT

3398 SEQ ID NO: 3565 7.3 -17.5 56.3 -24 -0.6 -8.2 AGAGATAGCAAAGTCCTAAC

2450 SEQ ID NO:3566 7.4 -19.7 60 -27.1 0 -4.1 GTAGCAGACATCTCAGAGAT

2464 SEQ ID NO: 3567 7.4 -22.5 68.7 -29.2 -0.3 -8.1 CTCCAACAGAAACCACAGGG

2696 SEQ ID NO: 3568 7.4 -23.6 65.5 -30.5 -0.2 -3.7 TACCAGAAGGTGGTGAGTGC

125 SEQ ID NO: 3569 7.6 -24.9 72.7 -30.4 -2.1 -6.8 ATAAAGTGGAACGATCACCA

528 SEQ ID NO: 3570 7.7 -20.2 58.9 -27.1 -0.6 -5.9 TGGATCAGTGCTGAGCCTAT

410 SEQ ID NO: 3571 7.9 -25.8 74.7 -33.1 2.3 -9.1 CACAGGGGACTGGAGAAGAA

2683 SEQ ID NO: 3572 7.9 -22.5 65 -27.7 -2.7 -5.4 AGAGCAGCAGACAGCTGCAG

2496 SEQ ID NO: 3573 8 -26.3 76.3 -27.7 -6.6 -13.8 TGTGCAATTAAGAATACATA

3485 SEQ ID NO: 3574 8 -16.3 52.2 -24.3 0 -5.4 TCAGAGATAGCAAAGTCCTA

2452 SEQ ID NO: 3575 8.1 -21.3 64.2 -29.4 0 -4.1 AGTAGCAGACATCTCAGAGA

2465 SEQ ID NO: 3576 8.1 -22.5 69.1 -30 -0.3 -7.2 GATTTAAAAAGATCTCTGGT

2595 SEQ ID NO: 3577 8.2 -17.3 54.8 -25.5 0 -6.3 CAGAAACCACAGGGGACTGG

2690 SEQ ID NO: 3578 8.2 -24.2 67.4 -29.7 -2.7 -7.2 GAAGACAGTGGGTTGAAGCA

1083 SEQ ID NO:3579 8.3 -22.7 66.8 -31 0 -4.1 GACATCTCAGAGATAGCAAA

2458 SEQ ID NO: 3580 8.3 -19.9 60.7 -27.4 -0.5 -8.5 TAGCAGACATCTCAGAGATA

2463 SEQ ID NO: 3581 8.3 -21 64.7 -28.5 -0.5 -8.5 AAAGTGGAACGATCACCATC

526 SEQ ID NO: 3582 8.4 -20.9 60.6 -28.2 -1 -6.1 ACAGAAACCACAGGGGACTG

2691 SEQ ID NO: 3583 8.4 -23.2 65.6 -29.3 -2.3 -7.3 CAACAGAAACCACAGGGGAC

2693 SEQ ID NO: 3584 8.4 -22.3 63 -29.9 -0.6 -3.7 ATCTCAGAGATAGCAAAGTC

2455 SEQ ID NO: 3585 8.6 -20 62.3 -27.9 -0.3 -8.1 AGCAGACATCTCAGAGATAG

2462 SEQ ID NO: 3586 8.6 -21.3 65.5 -29.1 -0.5 -8.5 CATCTCAGAGATAGCAAAGT

2456 SEQ ID NO: 3587 8.7 -20.3 62.1 -28.2 -0.5 -8.5 CAAGTAGCAGACATCTCAGA

2467 SEQ ID NO: 3588 8.8 -21.9 66.2 -30.1 -0.3 -4.1 AGCAGCAGACAGCTGCAGAA

2494 SEQ ID NO: 3589 8.8 -25.6 73.4 -27.8 -6.6 -13.8 TGTATATAATACATGTACTC

3399 SEQ ID NO: 3590 8.8 -16.6 54.2 -24 -1.3 -8.4 CAAGGGTATCATAAAGTGGA

538 SEQ ID NO: 3591 9 -19.7 59.8 -28.7 0 -2.8 ACATCTCAGAGATAGCAAAG

2457 SEQ ID NO: 3592 9.1 -19.3 59.6 -27.6 -0.5 -8.5

202 kcal/ kcal/ kcal/ kcal/ mol mol deg C mol mol kcal/mol IntraInter- duplex target molemoletotal formTm of struccular cular position oligo dnding ation Duplex ture oligo oligo

GTGCAATTAAGAATACATAT 3484 SEQ ID NO:3593 9.1 -16.3 52.2 -25.4 0 -5.4

CAGAGATAGCAAAGTCCTAA 2451 SEQ ID NO: 3594 9.2 -20.2 60.7 -29.4 0 -4.1

AGGGGACTGGAGAAGAACAT

2680 SEQ ID NO:3595 9.2 -21.8 63.8 -30.5 -0.2 -2.5 TCATAAAGTGGAACGATCAC

530 SEQ ID NO:3596 9.3 -18.6 56.5 -26.9 -0.9 -5.7

AAAAGCTCCGAAGCCCATAA

102 SEQ ID NO:3597 9.5 -23.2 62.9 -30.9 -1.8 -5

AGACATCTCAGAGATAGCAA

2459 SEQ ID NO:3598 9.5 -20.6 63 -29.3 -0.5 -8.5 TTTAAAAAGATCTCTGGTCC

2593 SEQ ID NO:3599 9.5 -19.1 58.6 -28.6 0 -6.3 TCCAACAGAAACCACAGGGG

2695 SEQ ID NO:3600 9.6 -23.9 66 -32.7 -0.6 -4.1

CAGACATCTCAGAGATAGCA

2460 SEQ ID NO:3601 9.7 -22 66.5 -31 -0.3 -8.3 GAGCAGCAGACAGCTGCAGA

2495 SEQ ID NO:3602 9.8 -26.9 77.4 -30.1 -6.6 -13.8

AAAGCTCCGAAGCCCATAAG 101 SEQ ID NO: 3603 9.9 -23.9 65 -32 -1.8 -5

AAGTAGCAGACATCTCAGAG 2466 SEQ ID NO:3604 9.9 -21.2 65.2 -30.5 -0.3 -4.8

CCAACAGAAACCACAGGGGA 2694 SEQ ID NO:3605 9.9 -24.1 65.9 -33.2 -0.6 -3.7

TAAAGTGGAACGATCACCAT 527 SEQ ID NO:3606 10.6 -20.2 58.9 -29.7 -1 -5.8

CATAAAGTGGAACGATCACC 529 SEQ ID NO: 3607 10.6 -20.2 58.9 -29.7 -1 -5.8

GCAGACATCTCAGAGATAGC

2461 SEQ ID NO:3608 10.7 -23.1 69.8 -33 -0.5 -8.5 ATACCGGAACAGCTCATGGG

21 SEQ ID NO: 3609 11.4 -24.9 69 -36.3 0 -7.1

ACCCTTACGAATCAGAAGGG 2650 SEQ ID NO:3610 11.6 -23.2 64.9 -31.8 -3 -10.4

ATTTAAAAAGATCTCTGGTC

2594 SEQ ID NO:3611 12.5 -17.1 54.8 -29.6 0 -6.3 TGCAATTAAGAATACATATA

3483 SEQ ID NO:3612 12.6 -14.8 49 -27.4 0 -4.7

TACCGGAACAGCTCATGGGC 20 SEQ ID NO:3613 12.9 -26.7 73 -38.6 -0.7 -9.3

CAGGGGACTGGAGAAGAACA

2681 SEQ ID NO:3614 13.6 -22.5 65 -34.3 -1.8 -5.2 ACAGGGGACTGGAGAAGAAC

2682 SEQ ID NO:3615 15.5 -22 64.4 -34.8 -2.7 -5.4

Example 15

Western blot analysis of ACSl protein levels

[00181] Western blot analysis (immunoblot analysis) is carried out using standard methods. Cells are harvested 16-20 h after oligonucleotide

203 treatment, washed once with PBS, suspended in Laemmli buffer (100 ul/well), boiled for 5 minutes and loaded on a 16% SDS-PAGE gel. Gels are run for 1.5 hours at 150 V, and transferred to membrane for western blotting. Appropriate primary antibody directed to ACSl is used, with a radiolabeled or fluorescently labeled secondary antibody directed against the primary antibody species. Bands are visualized using a PHOSPHORIMAGER™ (Molecular Dynamics, Sunnyvale CA).

204

Claims

WHAT IS CLAIMED IS:

1. An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding ACSl , wherein said antisense compound specifically hybridizes with and inhibits the expression of ACSl.

2. The antisense compound of claim 1 wherein said antisense compound is an antisense oligonucleotide.

3. The antisense oligonucleotide of claim 2 comprising a nucleic acid sequence selected from the group consisting of at least eight contiguous bases of SEQ ID NO:l - SEQ ID NO:3616.

4. The antisense oligonucleotide of claim 2 comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: l - SEQ ID NO:3616.

5. The antisense compound of claim 2, 3, or 4 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

6. The antisense compound of claim 5 wherein the modified internucleoside linkage is a phosphorothioate linkage.

7. The antisense compound of claim 2, 3, or 4 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

8. The antisense compound of claim 7 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety.

9. The antisense compound of claim 2, 3, or 4 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

10. The antisense compound of claim 9 wherein the modified nucleobase is a 5-methylcytosine.

205

11. The antisense compound of claim 2, 3, or 4 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

12. A composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. The composition of claim 12 further comprising a colloidal dispersion system.

14. The composition of claim 13 wherein the antisense compound is an antisense oligonucleotide.

15. A method of inhibiting the expression of ACS 1 in cells or tissues comprising contacting said cells or tissues with the antisense compound of claim 1 so that expression of ACSl is inhibited.

16. A method of treating a human having a disease or condition associated with ACSl comprising administering to said human a therapeutically or prophylactically effective amount of the antisense compound of claim 1 so that expression of ACSl is inhibited.

17. The method of claim 16 wherein the disease or condition is diabetes.

18. The method of claim 16 wherein the disease or condition is obesity.

19. The method of claim 16 wherein the disease or condition is a metabolic syndrome X.

20. The method of claim 16 wherein the disease or condition is a cardiovascular disorder.

21. The method of claim 16 wherein the disease or condition is cancer.

206 energy of which is described as 'intermolecular oligo'). Breaking up any self-structure amounts to a binding penalty. All compounds in Table 3 are chimeric oligonucleotides ("gapmers") 20 nucleotides in length, composed of a central "gap" region consisting often 2'deoxynucleotides, which is flanked on both sides (5' and 3' directions) by four-nucleotide "wings". The wings are composed of 2 '-methoxyethyl (2'-MOE) nucleotides. The internucleoside (backbone) linkages are phosphorothioate (P=S) throughout the oligonucleotide. Cytidine residues in the 2'-MOE wings are 5- methylcytidines. All cytidine residues are 5-methylcytidines.

86