WO2024165571A2

WO2024165571A2 - Inhibitors of expression and/or function

Info

Publication number: WO2024165571A2
Application number: PCT/EP2024/052934
Authority: WO
Inventors: Alan Victor WHITMORE; Sophia MALANDRAKI-MILLER; Ines DE SANTIAGO; Natalie PURSELL; Gaye Saginc GIANNOUSTAS
Original assignee: E-Therapeutics Plc
Priority date: 2023-02-06
Filing date: 2024-02-06
Publication date: 2024-08-15
Also published as: WO2024165571A3

Abstract

The present invention relates to inhibitors, and compositions containing inhibitors, and uses of the same in the treatment or prevention of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis.

Description

New PCT Patent Application Based on EP 23155094.8 e-therapeutics plc Voss.-Ref.: AG1023 PCT BS INHIBITORS OF EXPRESSION AND/OR FUNCTION FIELD The present invention provides inhibitors, such as nucleic acid compounds, such as siRNA, suitable for therapeutic use. Additionally, the present invention provides methods of making these compounds, as well as methods of using such compounds for the treatment of various diseases and condition BACKGROUND OF THE INVENTION Inhibitors, such as oligonucleoside/ oligonucleotide compounds which are inhibitors of gene expression and/or expression or function of other targets such as LNCRNAs, can have important therapeutic applications in medicine. Oligonucleotides/ oligonucleosides can be used to silence genes that are responsible for a particular disease. Gene-silencing prevents formation of a protein by inhibiting translation. Importantly, gene-silencing agents are a promising alternative to traditional small, organic compounds that inhibit the function of the protein linked to the disease. siRNA, antisense RNA, and micro-RNA are oligonucleoside /oligonucleotides that prevent the formation of proteins by gene-silencing. A number of modified siRNA compounds in particular have been developed in the last two decades for diagnostic and therapeutic purposes, including siRNA / RNAi therapeutic agents for the treatment of various diseases including central-nervous-system diseases, inflammatory diseases, metabolic disorders, oncology, infectious diseases, and ocular diseases. The present invention relates to inhibitors, such oligomers e.g. nucleic acids, e.g. oligonucleoside /oligonucleotide compounds, and their use in the treatment and / or prevention of disease. The SLC25A5 gene belongs to the ANT gene family, which itself belongs to the superfamily that includes genes encoding brown fat mitochondrial uncoupling proteins and mitochondrial phosphate carrier proteins. This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene, adenine nucleotide translocator 2 (ANT2), functions as a major constituent of the mitochondrial permeability-transition pore complex that catalyses the exchange of mitochondrial ATP with cytosolic ADP. As a result of its antiporter function, ANT2 maintains mitochondrial membrane potential by regulating ADP/ATP ratios in oxidative phosphorylation. ANT2 facilitates uncoupling of the mitochondrial membrane when acylated by SIRT4. Though uncoupling the membrane potential typically leads to apoptosis, ANT2 was found to be antiapoptotic. As a result, it is postulated to mediate the TFIIH-dependent response to DNA damage as a component of the MMS19-XPD. STATEMENTS OF INVENTION The invention is defined as in the claims and relates to, inter alia: In one aspect, the invention relates to an inhibitor of expression and / or function of SLC25A5/ANT2, wherein said inhibitor is conjugated to one or more ligand moieties. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said inhibitor is an siRNA oligomer. In another aspect, the invention relates to an inhibitor of expression and / or function of SLC25A5/ANT2, wherein said inhibitor is an siRNA oligomer. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said inhibitor comprises an siRNA oligomer conjugated to one or more ligand moieties. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said one or more ligand moieties comprise one or more GalNAc ligands or comprise one or more GalNAc ligand derivatives. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said one or more ligand moieties comprise one or more GalNAc ligand derivatives. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the target of the inhibitor is SLC25A5/ANT2. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the inhibitor is a nucleic acid for inhibiting expression of SLC25A5 comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand sequences as listed in Table 2. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the inhibitor is a nucleic acid for inhibiting expression of SLC25A5 comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand modified sequences as listed in Table 3. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises nucleosides 2-18 of any one of the sequences defined in claim 8 or 9, in particular wherein the first strand comprises nucleosides 2-18 of any one of the sequences defined in Tables 2 or 3. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the second strand sequences as listed in Table 2, and wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the second strand modified sequences as listed in Table 4, and wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises any one of the first strand sequences as listed in Table 2. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises any one of the first strand modified sequences as listed in Table 3. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises any one of the second strand sequences as listed in Table 2. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises any one of the first strand modified sequences as listed in Table 4. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises any one of the following sequences: SEQ ID NO:304, SEQ ID NO:323, SEQ ID NO:439, SEQ ID NO:453 and SEQ ID NO:496. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises any one of the following sequences: SEQ ID NO:856, SEQ ID NO:875, SEQ ID NO:991, SEQ ID NO:1005 and SEQ ID NO:1048. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises any one of the following sequences: SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises any one of the following sequences: SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324. In a further aspect, the invention relates to an inhibitor according to the invention, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 304 SEQ ID NO: 580 SEQ ID NO: 323 SEQ ID NO: 599 SEQ ID NO: 439 SEQ ID NO: 715 SEQ ID NO: 453 SEQ ID NO: 729 SEQ ID NO: 496 SEQ ID NO: 772 In a further aspect, the invention relates to an inhibitor according to the invention, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 304 SEQ ID NO: 580 In a further aspect, the invention relates to an inhibitor according to the invention, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 856 SEQ ID NO: 1132 SEQ ID NO: 875 SEQ ID NO: 1151 SEQ ID NO: 991 SEQ ID NO: 1267 SEQ ID NO: 1005 SEQ ID NO: 1281 SEQ ID NO: 1048 SEQ ID NO: 1324 In a further aspect, the invention relates to an inhibitor according to the invention, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 856 SEQ ID NO: 1132 In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA oligomer having a first and a second strand wherein: i) the first strand of the siRNA has a length in the range of 15 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 23 or 25; even more preferably 23; and / or ii) the second strand of the siRNA has a length in the range of 15 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 21 nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 23 nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 21 or 23 nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the duplex region of the nucleic acid is between 17 and 30 nucleosides in length, more preferably is 19 or 21 or 23 nucleosides in length. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the region of complementarity between the first strand and the portion of RNA transcribed from the SLC25A5 gene is between 17 and 30 nucleosides in length. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the nucleic acid further comprises one or more single-stranded nucleoside overhangs, optionally wherein the overhang is present on the first or second strand, preferably at the 3’ terminus of the first or second strand, and/or wherein the overhang comprises 1 to 4 nucleosides, more preferably 2 nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the nucleic acid is an siRNA oligonucleoside. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second sense strand further comprises one or more abasic nucleosides in a terminal region of the second strand, and wherein said abasic nucleoside(s) is / are connected to an adjacent nucleoside through a reversed internucleoside linkage. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises: i) 2, or more than 2, abasic nucleosides in a terminal region of the second strand; and / or ii) 2, or more than 2, abasic nucleosides in either the 5’ or 3’ terminal region of the second strand; and / or iii) 2, or more than 2, abasic nucleosides in either the 5’ or 3’ terminal region of the second strand, wherein the abasic nucleosides are present in an overhang as herein described; and / or iv) 2, or more than 2, consecutive abasic nucleosides in a terminal region of the second strand, wherein preferably one such abasic nucleoside is a terminal nucleoside; and / or v) 2, or more than 2, consecutive abasic nucleosides in either the 5’ or 3’ terminal region of the second strand, wherein preferably one such abasic nucleoside is a terminal nucleoside in either the 5’ or 3’ terminal region of the second strand; and / or vi) a reversed internucleoside linkage connects at least one abasic nucleoside to an adjacent basic nucleoside in a terminal region of the second strand; and / or vii) a reversed internucleoside linkage connects at least one abasic nucleoside to an adjacent basic nucleoside in either the 5’ or 3’ terminal region of the second strand; and / or viii) an abasic nucleoside as the penultimate nucleoside which is connected via the reversed linkage to the nucleoside which is not the terminal nucleoside (called the antepenultimate nucleoside herein); and / or ix) abasic nucleosides as the 2 terminal nucleosides connected via a 5’-3’ linkage when reading the strand in the direction towards that terminus; x) abasic nucleosides as the 2 terminal nucleosides connected via a 3’-5’ linkage when reading the strand in the direction towards the terminus comprising the terminal nucleosides; xi) abasic nucleosides as the terminal 2 positions, wherein the penultimate nucleoside is connected via the reversed linkage to the antepenultimate nucleoside, and wherein the reversed linkage is a 5-5’ reversed linkage or a 3’-3’ reversed linkage; xii) abasic nucleosides as the terminal 2 positions, wherein the penultimate nucleoside is connected via the reversed linkage to the antepenultimate nucleoside, and wherein either (1) the reversed linkage is a 5-5’ reversed linkage and the linkage between the terminal and penultimate abasic nucleosides is 3’5’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides; or (2) the reversed linkage is a 3-3’ reversed linkage and the linkage between the terminal and penultimate abasic nucleosides is 5’3’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the reversed internucleoside linkage is at a terminal region which is distal to the 5’ terminal region of the second strand, or at a terminal region which is distal to the 3’ terminal region of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the reversed internucleoside linkage is a 3’3 reversed linkage. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the reversed internucleoside linkage is a 5’5 reversed linkage. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second sense strand further comprises one or more abasic nucleosides in a terminal region of the second strand, and wherein said abasic nucleoside(s) is / are connected to an adjacent nucleoside through a reversed internucleoside linkage. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises 2 consecutive abasic nucleosides in the 5’ terminal region of the second strand, wherein one such abasic nucleoside is a terminal nucleoside at the 5’ terminal region of the second strand and the other abasic nucleoside is a penultimate nucleoside at the 5’ terminal region of the second strand, wherein: (a) said penultimate abasic nucleoside is connected to an adjacent first basic nucleoside in an adjacent 5’ near terminal region through a reversed internucleoside linkage; and (b) the reversed linkage is a 5-5’ reversed linkage; and (c) the linkage between the terminal and penultimate abasic nucleosides is 3’5’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides.12. An inhibitor, or inhibitor for use, according claim 10 or 11, wherein the reversed internucleoside linkage is at a terminal region which is distal to the 5’ terminal region of the second strand, or at a terminal region which is distal to the 3’ terminal region of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein (i) the first strand and the second strand each has a length of 23 nucleosides; (ii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in said 5’ near terminal region of the second strand, wherein a first phosphorothioate internucleoside linkage is present between said adjacent first basic nucleoside of (a) and an adjacent second basic nucleoside in said 5’ near terminal region of the second strand, and a second phosphorothioate internucleoside linkage is present between said adjacent second basic nucleoside and an adjacent third basic nucleoside in said 5’ near terminal region of the second strand; (iii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in both 5’ and 3’ terminal regions of the first strand, whereby a terminal nucleoside respectively at each of the 5’ and 3’ terminal regions of said first strand is each attached to a respective 5’ and 3’ adjacent penultimate nucleoside by a phosphorothioate internucleoside linkage, and each first 5’ and 3’ penultimate nucleoside is attached to a respective 5’ and 3’ adjacent antepenultimate nucleoside by a phosphorothioate internucleoside linkage; and (iv) the second strand of the nucleic acid is conjugated directly or indirectly to one or more ligand moieties at the 3’ terminal region of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein, wherein the 2 consecutive inverted abasic nucleosides in the 5’ terminal region of the second strand present as the following 5’ terminal motif

wherein: T represents a 2’Me ribose modification, B represents the nucleoside bases of the first two basic nucleosides in the 5' terminal region of the second strand, and Z represents the remaining 19 contiguous basic nucleosides of said second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein one or more nucleosides on the first strand and / or the second strand is / are modified, to form modified nucleosides. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the modification is a modification at the 2’-OH group of the ribose sugar, optionally selected from 2'-Me or 2’-F modifications. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first strand comprises a 2’-F at any of position 14, position 2, position 6, or any combination thereof, counting from position 1 of said first strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the second strand comprises a 2’-F modification at position 7 and / or 9, and / or 11 and / or 13, counting from position 1 of said second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the first and second strand each comprise 2'-Me and 2’-F modifications. In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA, wherein the siRNA comprises at least one thermally destabilizing modification, suitably at one or more of positions 1 to 9 of the first strand counting from position 1 of the first strand, and / or at one or more of positions on the second strand aligned with positions 1 to 9 of the first strand, wherein the destabilizing modification is selected from a modified unlocked nucleic acid (UNA) and a glycol nucleic acid (GNA), preferably a glycol nucleic acid. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the siRNA comprises at least one thermally destabilizing modification at position 7 of the first strand, counting from position 1 of the first strand. In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA, wherein the siRNA comprises 3 or more 2’-F modifications at positions 7 to 13 of the second strand, such as 4, 5, 6 or 72’-F modifications at positions 7 to 13 of the second strand, counting from position 1 of said second strand In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA, wherein said second strand comprises at least 3, such as 4, 5 or 6, 2’-Me modifications at positions 1 to 6 of the second strand, counting from position 1 of said second strand. In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA, wherein said first strand comprises at least 52’-Me consecutive modifications at the 3’ terminal region, preferably including the terminal nucleoside at the 3’ terminal region, or at least within 1 or 2 nucleosides from the terminal nucleoside at the 3’ terminal region. In a further aspect, the invention relates to an inhibitor according to the invention, which is an siRNA wherein said first strand comprises 72’-Me consecutive modifications at the 3’ terminal region, preferably including the terminal nucleoside at the 3’ terminal region. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the siRNA oligomer further comprises one or more phosphorothioate internucleoside linkages. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said one or more phosphorothioate internucleoside linkages are respectively between at least three consecutive positions in a 5’ or 3’ near terminal region of the second strand, whereby said near terminal region is preferably adjacent said terminal region wherein said one or more abasic nucleosides of said second strand is / are located as defined herein. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said one or more phosphorothioate internucleoside linkages are respectively between at least three consecutive positions in a 5’ and / or 3’ terminal region of the first strand, whereby preferably a terminal position at the 5’ and / or 3’ terminal region of said first strand is attached to its adjacent position by a phosphorothioate internucleoside linkage. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the oligomer is an siRNA and the second strand of the siRNA is conjugated directly or indirectly to one or more ligand moiety(s), wherein said ligand moiety is typically present at a terminal region of the second strand, preferably at the 3’ terminal region thereof. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the ligand moiety comprises i) one or more GalNAc ligands; and / or ii) one or more GalNAc ligand derivatives; and / or iii) one or more GalNAc ligands and / or GalNAc ligand derivatives conjugated to said siRNA through a linker. In a further aspect, the invention relates to an inhibitor according to the invention, wherein said one or more GalNAc ligands and / or GalNAc ligand derivatives are conjugated directly or indirectly to the 5’ or 3’ terminal region of the second strand of the siRNA oligomer, preferably at the 3’ terminal region thereof. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the ligand moiety comprises

. In a further aspect, the invention relates to an inhibitor according to the invention, comprising the structure:

wherein: R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1- 3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; m is an integer of from 1 to 6; n is an integer of from 1 to 10; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety. In a further aspect, the invention relates to an inhibitor according to the invention, comprising the structure , wherein oligonucleotide represents the contiguous nucleosides of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, comprising the structure

wherein: r and s are independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety. In a further aspect, the invention relates to an inhibitor according to the invention, comprising the structure

, wherein oligonucleotide represents the contiguous nucleosides of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, wherein the structure is conjugated to the 3’ terminal region of the second strand. In a further aspect, the invention relates to an inhibitor according to the invention, formulated as a pharmaceutical composition with an excipient and / or carrier. In another aspect, the invention relates to a pharmaceutical composition comprising an inhibitor according to one or more preceding aspects, in combination with a pharmaceutically acceptable excipient or carrier. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, further comprising a GLP-1 agonist and/or a THR-beta agonist. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, wherein the GLP-1 agonist is a GLP-1/GIP dual agonist, a GLP-1/FGF21 dual agonist, a GLP-1/GCGR dual agonist, or a GLP-1/GIP/GCGR triple agonist. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, wherein the GLP-1 agonist is semaglutide. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, wherein the THR-beta agonist is resmetirom. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, wherein the GLP-1/GIP dual agonist is tirzepatide. In a further aspect, the invention relates to the pharmaceutical composition according to the invention, further comprising one or more of: an amylin receptor agonist (such as pramlintide), and/or a dual amylin + calcitonin receptor agonist, and/or a glucagon receptor agonist, and/or an FXR receptor agonist (such as cilofexor or obeticholic acid), and/or an FGF-21 analogue or FGF-21 receptor agonist (such as efruxifermin), and/or an FGF-19 analogue or FGF-19 receptor agonist (such as aldafermin), and/or a galectin 3 inhibitor (such as belapectin), and/or a PPAR ^ agonist (such as elafibrinor), and/or a PPAR ^ agonist (such as pioglitazone or rosiglitazone), and/or a mixed PPAR ^ and/or ^ and/or ^ agonist, and/or a pan PPAR ^ ^ ^ agonist (such as lanafibranor), and/or an acetyl CoA desaturase activator, and/or an ASK1 inhibitor (such as selonsertib), and/or an LOXL2 inhibitor (such as simtuzumab), and/or a dual CCR2/5 inhibitor (such as cenicriviroc), and/or an inhibitor of an enzyme in the de novo lipogenesis (DNL) pathway including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and/or an inhibitor of an enzyme in the cholesterol biosynthesis pathway (such as an HMGCoA reductase inhibitor, such as atorvastatin). In another aspect, the invention relates to an inhibitor according to the invention or a pharmaceutical composition according to the invention for use in therapy. In another aspect, the invention relates to an inhibitor according to the invention or a pharmaceutical composition according to the invention for use in the prevention and/or treatment of metabolic disease or disorder, such as a metabolic disease or disorder associated with non- alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or for use in reducing adipogenesis. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the inhibitor or the pharmaceutical composition is to be used in combination with a GLP-1 agonist and/or a THR- beta agonist. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the GLP-1 agonist is a GLP-1/GIP dual agonist, a GLP-1/FGF21 dual agonist, a GLP-1/GCGR dual agonist, or a GLP- 1/GIP/GCGR triple agonist. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the GLP-1 agonist is semaglutide. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the THR-beta agonist is resmetirom. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the GLP-1/GIP dual agonist is tirzepatide. In a further aspect, the invention relates to an inhibitor for use according to the invention or a pharmaceutical composition for use according to the invention, wherein the inhibitor or the pharmaceutical composition is to be used in combination with one or more of: an amylin receptor agonist (such as pramlintide), and/or a dual amylin + calcitonin receptor agonist, and/or a glucagon receptor agonist, and/or an FXR receptor agonist (such as cilofexor or obeticholic acid), and/or an FGF-21 analogue or FGF-21 receptor agonist (such as efruxifermin), and/or an FGF-19 analogue or FGF-19 receptor agonist (such as aldafermin), and/or a galectin 3 inhibitor (such as belapectin), and/or a PPAR ^ agonist (such as elafibrinor), and/or a PPAR ^ agonist (such as pioglitazone or rosiglitazone), and/or a mixed PPAR ^ and/or ^ and/or ^ agonist, and/or a pan PPAR ^ ^ ^ agonist (such as lanafibranor), and/or an acetyl CoA desaturase activator, and/or an ASK1 inhibitor (such as selonsertib), and/or an LOXL2 inhibitor (such as simtuzumab), and/or a dual CCR2/5 inhibitor (such as cenicriviroc), and/or an inhibitor of an enzyme in the de novo lipogenesis (DNL) pathway including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and/or an inhibitor of an enzyme in the cholesterol biosynthesis pathway (such as an HMGCoA reductase inhibitor, such as atorvastatin). In another aspect, the invention relates to the use of SLC25A5/ANT2 as a target for identifying one or more therapeutic agents for the treatment or prevention of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or for reducing adipogenesis. In another aspect, the invention relates to a method of treating or preventing metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or a method of reducing adipogenesis, which comprises administering to a patient an inhibitor of expression and/or function of SLC25A5/ANT2, such as an inhibitor according to the invention. In a further aspect, the invention relates to a method according to the invention, wherein the inhibitor of expression and/or function of SLC25A5/ANT2 is administered together with a GLP- 1 agonist and/or a THR-beta agonist. In a further aspect, the invention relates to a method according to the invention, wherein the GLP-1 agonist is a GLP-1/GIP dual agonist, a GLP-1/FGF21 dual agonist, a GLP-1/GCGR dual agonist, or a GLP-1/GIP/GCGR triple agonist. In a further aspect, the invention relates to a method according to the invention, wherein the GLP-1 agonist is semaglutide. In a further aspect, the invention relates to a method according to the invention, wherein the GLP-1/GIP dual agonist is tirzepatide. In a further aspect, the invention relates to a method according to the invention, wherein the THR-beta agonist is resmetirom. In a further aspect, the invention relates to a method according to the invention, wherein the inhibitor of expression and/or function of SLC25A5/ANT2 is administered together with one or more of: an amylin receptor agonist (such as pramlintide), and/or a dual amylin + calcitonin receptor agonist, and/or a glucagon receptor agonist, and/or an FXR receptor agonist (such as cilofexor or obeticholic acid), and/or an FGF-21 analogue or FGF-21 receptor agonist (such as efruxifermin), and/or an FGF-19 analogue or FGF-19 receptor agonist (such as aldafermin), and/or a galectin 3 inhibitor (such as belapectin), and/or a PPAR ^ agonist (such as elafibrinor), and/or a PPAR ^ agonist (such as pioglitazone or rosiglitazone), and/or a mixed PPAR ^ and/or ^ and/or ^ agonist, and/or a pan PPAR ^ ^ ^ agonist (such as lanafibranor), and/or an acetyl CoA desaturase activator, and/or an ASK1 inhibitor (such as selonsertib), and/or an LOXL2 inhibitor (such as simtuzumab), and/or a dual CCR2/5 inhibitor (such as cenicriviroc), and/or an inhibitor of an enzyme in the de novo lipogenesis (DNL) pathway including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and/or an inhibitor of an enzyme in the cholesterol biosynthesis pathway (such as an HMGCoA reductase inhibitor, such as atorvastatin). In another aspect, the invention relates to the use of an inhibitor according to the invention or a pharmaceutical composition according to the invention, in the preparation of a medicament for the treatment of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or for reducing adipogenesis In another aspect, the invention relates to SLC25A5/ANT2 for use as a biomarker of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis. In another aspect, the invention relates to SLC25A5/ANT2 for use in an in vivo method of predicting susceptibility to prevention and/or treatment of metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis, typically by monitoring the sequence and/ or level of expression and / or function of SLC25A5/ANT2 in a sample obtained from a patient. In another aspect, the invention relates to a method of predicting susceptibility to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis, in a patient, said method comprising: (a) obtaining a sample from the patient, (b) detecting the sequence and / or expression and / or function of SLC25A5/ANT2 in said sample obtained from the patient, (c) predicting susceptibility to a disease related to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis, based on the sequence and / or expression and / or function of SLC25A5/ANT2 in said sample obtained from the patient, (d) preferably administering to the diagnosed patient an effective amount of an inhibitor of SLC25A5/ANT2. FIGURES Figure 1a: An exemplary linear configuration for a conjugate. Figure 1b: An exemplary branched configuration for a conjugate. Figure 2: Linker and ligand portions of constructs suitable for use according to the present invention including tether 1a. While Figure 2 depicts the linker to be conjugated to an oligonucleotide, it is to be understood that the present invention also encompasses conjugates of the same linker with an oligonucleoside as disclosed herein. It should also be understood that while Figure 2 depicts as a product molecules based on the linker and ligand portions as specifically depicted in Figure 2 attached to an oligonucleoside moiety as also depicted herein, this product may alternatively further comprise, or consist essentially of, molecules wherein the linker and ligand portions are essentially as depicted in Figure 2 attached to an oligonucleoside moiety but having the F substituent as shown in Figure 2 on the cyclo-octyl ring replaced by a substituent, which could occur as a result of hydrolytic displacement, such as an OH substituent, or the OH substituent could be synthesized as a linker in its own right. In this way, (a) tether 1a constructs can consist essentially of molecules having linker and ligand portions specifically as depicted in Figure 2, with a F substituent on the cyclo- octyl ring; or (b) tether 1a constructs can consist essentially of molecules having linker and ligand portions essentially as depicted in Figure 2 but having the F substituent as shown in Figure 2 on the cyclo-octyl ring replaced by an OH substituent, or (c) tether 1a constructs can comprise a mixture of molecules as defined in (a) and/or (b). Figure 3: Linker and ligand portions of constructs suitable for use according to the present invention including tether 1b. While Figure 3 depicts the linker to be conjugated to an oligonucleotide, it is to be understood that the present invention also encompasses conjugates of the same linker with an oligonucleoside as disclosed herein. The comments made in relation to Figure 2 and the possible replacement of the F substituent as shown in Figure 2 on the cyclo-octyl ring replaced by a substituent, which could occur as a result of hydrolytic displacement, such as an OH substituent, or the OH substituent could be synthesized as a linker in its own right, apply equally to tether 1b constructs. In this way, (a) tether 1b constructs can consist essentially of molecules having linker and ligand portions specifically as depicted in Figure 3, with a F substituent on the cyclo-octyl ring; or (b) tether 1b constructs can consist essentially of molecules having linker and ligand portions essentially as depicted in Figure 3 but having the F substituent as shown in Figure 3 on the cyclo-octyl ring replaced by an OH substituent, or (c) tether 1b constructs can comprise a mixture of molecules as defined in (a) and/or (b). Figure 4: Linker and ligand portions of constructs suitable for use according to the present invention including tether 2a. While Figure 4 depicts the linker to be conjugated to an oligonucleotide, it is to be understood that the present invention also encompasses conjugates of the same linker with an oligonucleoside as disclosed herein. Figure 5: Linker and ligand portions of constructs suitable for use according to the present invention including tether 2b. While Figure 5 depicts the linker to be conjugated to an oligonucleotide, it is to be understood that the present invention also encompasses conjugates of the same linker with an oligonucleoside as disclosed herein. Figure 6: Formulae described in Sentences 1-101 disclosed herein. Figure 7: Formulae described in Clauses 1-56 disclosed herein. Figures 8a and 8b: Inverted abasic constructs that can be used with nucleic acid sequences according to the present invention as described herein. For Figure 8a, a GalNAc linker is attached to the 5’ end region of the sense strand in use (not depicted in Figure 8a). For Figure 8b, a GalNAc linker is attached to the 3’ end region of the sense strand in use (not depicted in Figure 8b). iaia as shown at the 3’ end region of the sense strand in Figure 8a represents (i) two abasic nucleosides provided as the penultimate and terminal nucleosides at the 3’ end region of the sense strand, (ii) wherein a 3’-3’ reversed linkage is provided between the antepenultimate nucleoside (namely at position 21 of the sense strand, wherein position 1 is the terminal 5’ nucleoside of the sense strand) and the adjacent penultimate abasic residue of the sense strand, and (iii) the linkage between the terminal and penultimate abasic nucleosides is 5’-3’ when reading towards the 3’ end region comprising the terminal and penultimate abasic nucleosides. iaia as shown at the 5’ end region of the sense strand in Figure 8b represents (i) two abasic nucleosides provided as the penultimate and terminal nucleosides at the 5’ end region of the sense strand, (ii) wherein a 5’-5’ reversed linkage is provided between the antepenultimate nucleoside (namely at position 1 of the sense strand, not including the iaia motif at the 5’ end region of the sense strand in the nucleoside position numbering on the sense strand) and the adjacent penultimate abasic residue of the sense strand, and (iii) the linkage between the terminal and penultimate abasic nucleosides is 3’-5’ when reading towards the 5’ end region comprising the terminal and penultimate abasic nucleosides. Figures 9a and 9b: Duplex constructs according to Table 5. Figures 10: Summary of mRNA and protein knockdown effects of a single dose of GalNAc- siRNAs, ETX-M00001397, ETX-M00001570, ETX-M00001378, ETX-M00001513, and ETX- M00001527 (1 mg/kg or 3 mg/kg) in mouse liver tissues. As a negative control, a non-target specific siRNA was used. The y-axis values are the relative mRNA or protein expression and data is normalized to the saline control group (n=4). Each data point represents the relative mRNA or protein expression as Mean ± SEM from n=4 experiment. Figure 11: Liver samples stained with H&E were given a score for NAFLD Activity Score (NAS) using the clinical criteria outlined by Kleiner et al. (2005). Total NAS represents the sum of scores for steatosis, inflammation, and ballooning, and ranges from 0-8. NAS score was determined by Gubra Histopathological Objective Scoring Technology (GHOST) deep learning app developed by Gubra using the VIS software (Visiopharm, Denmark) for a more accurate and objective method for staging disease in DIO-NASH mouse models. Results are presented as change in NAS score (improvement or worsening) at study termination compared to the pre-dose biopsy. Also shown is the percentage of animals with at least a 1- or 2-point improvement in NAS. Figure 12: ALT and AST were measured in plasma samples after 12 weeks ETX-312 (ETX- M00001378) treatment using commercial kits (Roche Diagnostics), on the cobas c501 autoanalyzer. ALT and AST levels were increased in DIO-NASH mice (vehicle sc, siCtrl, vehicle PO). Treatment with ETX-312 (ETX-M00001378) alone or in combination with semaglutide or resmetirom significantly reduced both ALT and AST levels. Results are presented as absolute levels as Mean ± SEM from n=16 experiment. * p < 0.05; *** p < 0.001; **** p < 0.0001 Figure 13: TIMP-1 and PIIINP are non-invasive blood biomarkers for NAFLD/NASH that predict hepatic fibrosis. TIMP-1 was measured in plasma collected in EDTA tubes using a commercial ELISA kit (R&D Systems). PIIINP was measured in plasma collected in EDTA tubes using a commercial ELISA kit (Cusabio). TIMP-1 and PIIINP levels were increased in DIO-NASH mice (vehicle sc, siCtrl, vehicle PO). Treatment with ETX-312 (ETX-M00001378) alone or in combination with semaglutide or resmetirom significantly reduced both TIMP-1 and PIIINP levels. Results are presented as absolute levels as Mean ± SEM from n=16 experiment. An outlier analysis was conducted by comparing the studentised residuals of the linear model fitted to the subcutaneous treatment subset of the data to the critical Bonferroni alpha level (0.05/88 = ~0.00057). One animal in the semaglutide group was identified as an outlier which was verified by an influence analysis. This animal was concluded as both highly outlying and influential and was excluded from all TIMP-1 and PIIINP analysis. * p < 0.05; *** p < 0.001; **** p < 0.0001 Figure 14: Terminal liver weight to body weight ratio demonstrates hepatomegaly in DIO- NASH mice. Treatment with ETX-312 (ETX-M00001378) alone or in combination with semaglutide or resmetirom significantly reduced liver to body weight ratio. Results are presented as percent liver:body weight as Mean ± SEM from n=16 experiment. ** p < 0.01; **** p < 0.0001 DETAILED DESCRIPTION The present invention, inter alia, provides inhibitors, for example oligomers such as nucleic acids, such as inhibitory RNA molecules (which may be referred to as iRNA or siRNA ), and compositions containing the same which can affect expression of a target, for example by binding to mRNA transcribed from a gene. The target may be within a cell, e.g. a cell within a subject, such as a human. The inhibitors can be used to prevent and/or treat medical conditions associated with the e.g. the expression of a target gene. In particular the present invention identifies inhibitors of expression and/or function of SLC25A5/ANT2 as useful in the prevention and/or treatment of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis. ADP/ATP translocase 2 (ANT2) is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome. This protein functions as an antiporter for ADP/ATP exchange between the mitochondrial matrix and cytoplasm. The present invention relates to an inhibitor of expression and/or function of SLC25A5/ANT2. Accordingly, in certain embodiments, the invention relates to an inhibitor of expression of the SLC25A5 gene, such as an siRNA that targets an mRNA transcribed from the SLC25A5 gene. In certain embodiments, the invention relates to an inhibitor of function of the gene product ANT2. Both options are encompassed when it referred herein to an inhibitor of SLC25A5/ANT2 or an inhibitor of the invention. In humans, ANT2 is encoded by the SLC25A5 gene (SEQ ID NO:1381). SEQ ID NO:1381 (SLC25A5) ATCGGCCATTTGCTTCGCTCCGCCCCGCAGCGCCGGAGTCAAAGCCGGTTCCCGGCCCAGTCCCGTCCT GCAGCAGTCTGCCTCCTCTTTCAACATGACAGATGCCGCTGTGTCCTTCGCCAAGGACTTCCTGGCAGG TGGAGTGGCCGCAGCCATCTCCAAGACGGCGGTAGCGCCCATCGAGCGGGTCAAGCTGCTGCTGCAG GTACGTCCTGGGATCCAGGAGCCCAACCAGGAAGTGGGGGGAAGGGTCGCACAGAAGGCGGGCGCCC GAGGGGTGGCGGGGAGCGAACTCTAAAGACATGGCCAGGGAAGCGGCTTAGGAGAGGCCAGAGCGG GGCGCAGAGGCAGAACAGAAGTCAAACTGGTGGGAGGCGCCTTTAGTGACCTGAAGTAGTGAGTCTA GGAAGGGGCCGGGGGCAGAGGGCAGGACCAGGCTCTCGGCATCTCCGAGGCGGCGGACTCGGATGG AGCAGTTTCTGAGTGACGGCCTCCCCGGGCCTGGGCGTCAAGGGCGAAGGCCGAAAGCCGGCGTTAG AAAGAGGAACGCCAGTTCTTACCGAAGACCTCAAGGTCGCGGCAAGGAGATAACTGCCCGGGGGAGG CCATGCGCCCGGGTCCAGCGGCCTCCCAGCCCGCGGACGCGCTCAAACCTCGCCGGGCCGGAAGCCG GCGCCGGGAAGCGCGTGTGCCTTTTACGTCCGCCCCCGCGCAGCCGCGGCCGCTGCCGCCGCGTCTCC GCCTGCCTCCCTGCGCCGCGCGCTCTCCAGTGCCGGCTCTAGAGGGCGCTCCTGGGCTAGCGTGTAGG GCTGGCGGCGGCGGCGCTCGGGTCACCTCTGGGAGCGGAGTGGGGGCGGAGCGAGACGGAAGCAGCT CAGGAGACTTGAGGCGTAGGCTGCGGTCCCCAAGGTGACCGCGCCCTATGTGGGACTCGCCCTAATGC CTCTGAACCTGGGTTTGAGGTAATGACCTTTCTCCTAGGTCTGAAGGTCACGGGTCCGCTGGAGGATG CCCCCTCTCCACTCAGAGGGGTGGAGGCTTAATGCTACTGGTGCAGATCACCTCTTCCCCTGTGACAGC CTCAGAGGGTTGGGAGGGTCCAGCCAGTATGATATACGAAGACTAGATTTGAGAGAGGGGAGCCTAC CTTAAAGGGCATTGATCGAGATGGCATAAGCTCTTCTCTTTCCCTTCCCCATGGTTATAACTGTCCCTG TTGGCTTCCTTCCTGTCTGTTAGGTGCAGCATGCCAGCAAGCAGATCACTGCAGATAAGCAATACAAA GGCATTATAGACTGCGTGGTCCGTATTCCCAAGGAGCAGGGAGTTCTGTCCTTCTGGCGCGGTAACCT GGCCAATGTCATCAGATACTTCCCCACCCAGGCTCTTAACTTCGCCTTCAAAGATAAATACAAGCAGA TCTTCCTGGGTGGTGTGGACAAGAGAACCCAGTTTTGGCTCTACTTTGCAGGGAATCTGGCATCGGGT GGTGCCGCAGGGGCCACATCCCTGTGTTTTGTGTACCCTCTTGATTTTGCCCGTACCCGTCTAGCAGCT GATGTGGGTAAAGCTGGAGCTGAAAGGGAATTCCGAGGCCTCGGTGACTGCCTGGTTAAGATCTACA AATCTGATGGGATTAAGGGCCTGTACCAAGGCTTTAACGTGTCTGTGCAGGGTATTATCATCTACCGA GCCGCCTACTTCGGTATCTATGACACTGCAAAGGGTAAGTTTGCTGTGGGCTTTAACGTTGTGTTCTTA GGAGACAGTTTAAAAGAGCATTGTACCAACCTAACAGTCCAAGAGCTAAAGAGTTGTTTTTTTAATTG CTAAAGGAAGCCAAGATCATCCAATGCAACCCTTGTGTACAGATGACGTGTTTAGGGGATGTGGGGA AAGGAAGTCAGTAAAACTCTGCTTTTTGGTAAAAGCATCTCTTTCCTATTCCCAGGAATGCTTCCGGAT CCCAAGAACACTCACATCGTCATCAGCTGGATGATCGCACAGACTGTCACTGCTGTTGCCGGGTTGAC TTCCTATCCATTTGACACTGTTCGCCGCCGCATGATGATGCAGTCAGGGCGCAAAGGAAGTAAGTTCC ACTTGAGCAGAAGATAAAGTTGTAGTCGTGGGGCAATCTGCTGCCACAAACTGGTGATACATACCTTT AAAATGGCTGTCTGTCCAAGTCAAGGGATGGGGTTGATAGCATCTGTGTCTGTTCCACAACTGCCTTTG AGCTGGCCCTTCAGATGCCTATGAATGAGGGTGCTTAAATGGTGTTAGAGGTTAAGACCAATGGGTAG TCTGTATTCCTGTGGTCATAGCATTAATATTTCAGTGTTGCCCATGCTAATGTGTGAATGTTGGATTTA AAGCTGACGTTCTTAGAGGTGGGGCTCTGCTTTATTTAGCCTAGTGAATCTTAGGATTTTTCATCGGCC TTCAGTCACTAACTCCATGTCTTTATTCTTTGCAGCTGACATCATGTACACAGGCACGCTTGACTGCTG GCGGAAGATTGCTCGTGATGAAGGAGGCAAAGCTTTTTTCAAGGGTGCATGGTCCAATGTTCTCAGAG GCATGGGTGGTGCTTTTGTGCTTGTCTTGTATGATGAAATCAAGAAGTACACATAAGTTATTTCCTAGG ATTTTTCCCCCTGTGAACAGGCATGTTGTATTATATAACATATCTTGAGCATTCTTGACAGACTCCTGG CTGTCAGTTTCTCAGTGGCAACTATTTACTGGTTGAAAATGGGAAGCAATAATATTCATCTGACCAGTT TTCTCTTAAAGCCATTTCCATGATGATGATGATGGGACTCAATTGTATTTTTTATTTCAGTCACTCCTGA TAAATAACAAATTTGGAGAAATAAAAATATCTAAAATAAATTTTGTCTGCAGTATATTTTCATATAAA AATGCATATTTGAGTGCTACATTCGAATAAATACTACCTTTTTAGTGAA The inventors employed network analysis that allows them to allocate multiple genes or proteins to a smaller number of driver processes; and to mine these processes for impactful drug targets. The approach takes advantage of information that is usually ignored in standard gene set analyses – the known and predicted interactions between genes (and proteins) and the inclusion of other genes in the same or related pathways. In particular, the inventors analysed Genome Wide Association Studies (GWAS) metanalyses for Non-Alcoholic Fatty Liver Disease (NAFLD) using network models which highlighted SLC25A5/ANT2 as a preferred target for NAFLD among other known targets associated with NAFLD. The inhibition disclosed herein may be of the gene SLC25A5 or protein ANT2 resulting from expression of the SLC25A5 gene and reference to SLC25A5/ANT2 hereby explicitly incorporates a reference to inhibition of the expression or function of the gene and, separately, of the protein product. DEFINITIONS The “first strand”, also called the antisense strand or guide strand herein and which can be used interchangeably herein, refers to the nucleic acid strand, e.g. the strand of an siRNA, e.g. a dsiRNA, which includes a region that is substantially complementary to a target sequence, e.g. to an mRNA. As used herein, the term "region of complementarity" refers to the region on the antisense strand that is substantially complementary to a sequence, for example a target sequence. Where the region of complementarity is not fully complementary to the target sequence, the mismatches can be in the internal or terminal regions of the molecule. In some embodiments, a double stranded nucleic acid e.g. an siRNA agent of the invention includes a nucleotide mismatch in the antisense strand. The “second strand” (also called the sense strand or passenger strand herein, and which can be used interchangeably herein), refers to the strand of a nucleic acid e.g. siRNA that includes a region that is substantially complementary to a region of the antisense strand as that term is defined herein. In the context of molecule comprising a nucleic acid provided with a ligand moiety, optionally also with a linker moiety, the nucleic acid of the invention may be referred to as an oligonucleotide moiety or oligonucleoside moiety Oligonucleotides are short nucleic acid polymers. Whilst oligonucleotides contain phosphodiester bonds between the nucleoside component thereof (base plus sugar), the present invention is not limited to oligonucleotides always joined by such a phosphodiester bond between adjacent nucleosides, and other oligomers of nucleosides joined by bonds which are bonds other than a phosphate bond are contemplated. For example, a bond between nucleotides may be a phosphorothioate bond. Therefore, the term “oligonucleoside” herein covers both oligonucleotides and other oligomers of nucleosides. An oligonucleoside which is a nucleic acid having at least a portion which is an oligonucleotide is preferred according to the present invention. An oligonucleoside having one or more, or a majority of, phosphodiester backbone bonds between nucleosides is also preferred according to the present invention. An oligonucleoside having one or more, or a majority of, phosphodiester backbone bonds between nucleosides, and also having one or more phosphorothioate backbone bonds between nucleosides (typically in a terminal region of the first and / or second strands) is also preferred according to the present invention. It is preferred herein that the nucleic acid according to the invention is a double stranded oligonucleoside comprising one or more phosphorothioate backbone bonds between nucleosides. Accordingly, in all instances in which the present application refers to an oligonucleotide, particularly in the chemical structures disclosed herein, the oligonucleotide may equally be an oligonucleoside as defined herein. In some embodiments, a double stranded nucleic acid e.g. siRNA agent of the invention includes a nucleoside mismatch in the sense strand. In some embodiments, the nucleoside mismatch is, for example, within 5, 4, 3, 2, or 1 nucleosides from the 3 '-end of the nucleic acid e.g. siRNA. In another embodiment, the nucleoside mismatch is, for example, in the 3'- terminal nucleoside of the nucleic acid e.g. siRNA. A "target sequence" (which may be called a target RNA or a target mRNA) refers to a contiguous portion of the nucleoside sequence of an mRNA molecule formed during the transcription of a gene, including mRNA that is a product of RNA processing of a primary transcription product, or can be a contiguous portion of the nucleotide sequence of any RNA molecule such as a LNCRNA which it is desired to inhibit. The target sequence may be from about 10-35 nucleosides in length, e.g., about 15-30 nucleosides in length. For example, the target sequence can be from about 15-30 nucleosides, 15- 29, 15-28, 15-27, 15-26, 15-25, 15-24, 15-23, 15-22, 15-21, 15-20, 15-19, 15-18, 15-17, 18-30, 18-29, 18- 28, 18-27, 18-26, 18-25, 18-24, 18-23, 18-22, 18-21, 18-20, 19-30, 19-29, 19-28, 19- 27, 19-26, 19-25, 19-24, 19-23, 19-22, 19-21, 19-20, 20-30, 20-29, 20-28, 20-27, 20-26, 20-25, 20-24, 20-23, 20-22, 20- 21, 21-30, 21-29, 21-28, 21-27, 21-26, 21-25, 21-24, 21-23, or 21-22 nucleosides in length. Ranges and lengths intermediate to the above recited ranges and lengths are also contemplated to be part of the invention. The term “ribonucleoside” or “nucleoside” can also refer to a modified nucleoside as further detailed below. A nucleic acid can be a DNA or an RNA, and can comprise modified nucleosides. RNA is a preferred nucleic acid. The terms "iRNA", “siRNA”, "RNAi agent," and "iRNA agent," "RNA interference agent" as used interchangeably herein, refer to an agent that contains RNA, and which mediates the targeted cleavage of an RNA transcript via an RNA-induced silencing complex (RISC) pathway. siRNA directs the sequence-specific degradation of mRNA through RNA interference (RNAi). A double stranded RNA is referred to herein as a "double stranded siRNA (dsiRNA) agent", "double stranded siRNA (dsiRNA) molecule", "double stranded RNA (dsRNA) agent", "double stranded RNA (dsRNA) molecule", "dsiRNA agent", "dsiRNA molecule", or "dsiRNA", which refers to a complex of ribonucleic acid molecules, having a duplex structure comprising two anti- parallel and substantially complementary nucleic acid strands, referred to as having "sense" and "antisense" orientations with respect to a target RNA. The majority of nucleosides of each strand of the nucleic acid, e.g. a dsRNA molecule, are preferably ribonucleosides, but in that case each or both strands can also include one or more non-ribonucleosides, e.g., a deoxyribonucleoside or a modified ribonucleoside. In addition, as used in this specification, an "siRNA" may include ribonucleosides with chemical modifications. The term "modified nucleoside" refers to a nucleoside having, independently, a modified sugar moiety, a modified internucleoside linkage, or modified nucleobase, or any combination thereof. Thus, the term modified nucleoside encompasses substitutions, additions or removal of, e.g., a functional group or atom, to internucleoside linkages, sugar moieties, or nucleobases. Any such modifications, as used in a siRNA type molecule, are encompassed by "iRNA" or "RNAi agent" or “siRNA” or “siRNA agent” for the purposes of this specification and claims. The duplex region of a nucleic acid of the invention e.g. a dsRNA may range from about 9 to 40 base pairs in length such as 9 to 36 base pairs in length, e.g., about 15- 30 base pairs in length, for example, about 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 base pairs in length, such as about 15-30, 15-29, 15-28, 15-27, 15- 26, 15-25, 15-24, 15-23, 15-22, 15-21, 15-20, 15-19, 15-18, 15-17, 18-30, 18-29, 18-28, 18- 27, 18-26, 18-25, 18-24, 18-23, 18-22, 18-21, 18-20, 19-30, 19-29, 19-28, 19-27, 19-26, 19-25, 19- 24, 19-23, 19-22, 19-21, 19-20, 20-30, 20-29, 20-28, 20-27, 20-26, 20-25, 20-24,20-23, 20-22, 20-21, 21- 30, 21-29, 21-28, 21-27, 21-26, 21-25, 21-24, 21-23, or 21-22 base pairs in length. The two strands forming the duplex structure may be different portions of one larger molecule, or they may be separate molecules e.g. RNA molecules. The term "nucleoside overhang" refers to at least one unpaired nucleoside that extends from the duplex structure of a double stranded nucleic acid. A ds nucleic acid can comprise an overhang of at least one nucleoside; alternatively, the overhang can comprise at least two nucleosides, at least three nucleosides, at least four nucleosides, at least five nucleosides, or more. A nucleoside overhang can comprise or consist of a nucleoside analog, including a deoxynucleoside. The overhang(s) can be on the sense strand, the antisense strand, or any combination thereof. Furthermore, the /nucleoside(s) of an overhang can be present on the 5'-end, 3'-end, or both ends of either an antisense or sense strand. In certain embodiments, the antisense strand has a 1-10 nucleoside, e.g., 0-3, 1-3, 2-4, 2-5, 4-10, 5-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleoside overhang at the 3'-end or the 5'-end. "Blunt" or "blunt end" means that there are no unpaired nucleoside at that end of the double stranded nucleic acid, i.e., no nucleoside overhang. The nucleic acids of the invention include those with no nucleoside overhang at one end or with no nucleoside overhangs at either end. Unless otherwise indicated, the term "complementary," when used to describe a first nucleoside sequence in relation to a second nucleoside sequence, refers to the ability of an oligonucleoside comprising the first nucleoside sequence to hybridize and form a duplex structure under certain conditions with an oligonucleoside or polynucleoside comprising the second nucleoside sequence, as will be understood by the skilled person. Such conditions can, for example, be stringent conditions, where stringent conditions can include: 400 mM NaCl, 40 mM PIPES pH 6.4, 1 mM EDTA, 50°C or 70°C for 12-16 hours followed by washing (see, e.g., "Molecular Cloning: A Laboratory Manual, Sambrook, et al. (1989) Cold Spring Harbor Laboratory Press). Complementary sequences within nucleic acid e.g. a dsiRNA, as described herein, include base- pairing of the oligonucleoside or polynucleoside comprising a first nucleoside sequence to an oligonucleoside or polynucleoside comprising a second nucleoside sequence over the entire length of one or both nucleoside sequences. Such sequences can be referred to as "fully complementary" with respect to each other herein. However, where a first sequence is referred to as "substantially complementary" or “partially complementary”with respect to a second sequence herein, the two sequences can be fully complementary, or they can form one or more mismatched base pairs, such as 2, 4, or 5 mismatched base pairs, but preferably not more than 5, while retaining the ability to hybridize under the conditions most relevant to their ultimate application, e.g., inhibition of gene expression via a RISC pathway. Overhangs shall not be regarded as mismatches with regard to the determination of complementarity. For example, a nucleic acid e.g. dsRNA comprising one oligonucleoside 17 nucleosides in length and another oligonucleoside 19 nucleosides in length, wherein the longer oligonucleoside comprises a sequence of 17 nucleosides that is fully complementary to the shorter oligonucleoside, can yet be referred to as "fully complementary". "Complementary" sequences, as used herein, can also include, or be formed entirely from, non- Watson-Crick base pairs or base pairs formed from non-natural and modified nucleosides, in so far as the above requirements with respect to their ability to hybridize are fulfilled. Such non- Watson-Crick base pairs include, but are not limited to, G:U Wobble or Hoogstein base pairing. The terms "complementary," "fully complementary" and "substantially/partially complementary" herein can be used with respect to the base matching between the sense strand and the antisense strand of a nucleic acid e.g. dsiRNA, or between the antisense strand of a double stranded nucleic acid e.g. siRNA agent and a target sequence. Within the present invention, the second strand of the nucleic acid according to the invention, in particular a dsiRNA for inhibiting SLC25A5, is at least partially complementary to the first strand of said nucleic acid. In certain embodiments, a first and second strand of a nucleic acid according to the invention are partially complementary if they form a duplex region having a length of at least 17 base pairs and comprising not more than 1, 2, 3, 4, or 5 mismatched base pairs. In certain embodiments, a first and second strand of the nucleic acid according to the invention are partially complementary if they form a duplex region having a length of 19 base pairs and comprising not more than 1, 2, 3, 4, or 5 mismatched base pairs. In certain embodiments, a first and second strand of the nucleic acid according to the invention are partially complementary if they form a duplex region having a length of 21 base pairs comprising not more than 1, 2, 3, 4, or 5 mismatched base pairs. Alternatively, a first and second strand of the nucleic acid according to the invention are partially complementary if they form a duplex region having a length of at least 17 base pairs, wherein at least 14, 15, 16 or 17 of said base pairs are complementary base pairs, in particular Watson-Crick base pairs. In certain embodiments, a first and second strand of the nucleic acid according to the invention are partially complementary if they form a duplex region having a length of 19 base pairs, wherein at least 14, 15, 16, 17, 18 or all 19 base pairs are complementary base pairs, in particular Watson-Crick base pairs. In certain embodiments, a first and second strand of the nucleic acid according to the invention are partially complementary if they form a duplex region having a length of 21 base pairs, wherein at least 16, 17, 18, 19, 20 or all 21 base pairs are complementary base pairs, in particular Watson-Crick base pairs. As used herein, a nucleic acid that is "substantially complementary” or “partially complementary” to at least part of a messenger RNA (mRNA) refers to a polynucleoside that is substantially or partially complementary to a contiguous portion of the mRNA of interest (e.g., an mRNA encoding a gene). In certain embodiments, the contiguous portion of the mRNA is a sequence as listed in Table 1, i.e., any one of SEQ ID NOs:1-276. For example, a polynucleoside is complementary to at least a part of an mRNA of a gene of interest if the sequence is substantially or partially complementary to a non-interrupted portion of an mRNA encoding that gene. Accordingly, in some preferred embodiments, the antisense oligonucleosides as disclosed herein are fully complementary to the target gene sequence. In other embodiments, the antisense oligonucleosides disclosed herein are substantially or partially complementary to a target RNA sequence and comprise a contiguous nucleoside sequence which is at least about 80% complementary over its entire length to the equivalent region of the target RNA sequence, such as at least about 85%, 86%, 87%, 88%, 89%, about 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% complementary or 100% complementary. In certain embodiments, the first (antisense) strand of a nucleic acid according to the invention is partially or fully complementary to a contiguous portion of RNA transcribed from the SLC25A5 gene. In certain embodiments, the first strand of the nucleic acid according to the invention is partially or fully complementary to a contiguous portion of at least 17 nucleosides of the SLC25A5 mRNA. In certain embodiments, the first strand of the nucleic acid according to the invention is partially or fully complementary to a contiguous portion of 17, 18, 19, 20, 21, 22 or 23 nucleosides of the SLC25A5 mRNA. In certain embodiments, the first strand of the nucleic acid according to the invention is partially or fully complementary to a contiguous portion of 17, 18, 19, 20, 21, 22 or 23 nucleosides of any one of the sequences as listed in Table 1, i.e., any one of SEQ ID NOs: 1-276. In certain embodiments, the first (antisense) strand of the nucleic acid according to the invention is partially complementary to a contiguous portion of the SLC25A5 mRNA if it comprises a contiguous nucleoside sequence of at least 17 nucleosides, wherein at least 14, 15, 16 or 17 nucleosides of said contiguous nucleoside sequence are complementary to a contiguous portion of the SLC25A5 mRNA. In certain embodiments, the first strand of the nucleic acid according to the invention comprises a contiguous nucleoside sequence of at least 17 nucleosides, wherein at least 14, 15, 16 or 17 nucleosides of said contiguous nucleoside sequence are complementary to a contiguous portion of any one of the sequences listed in Table 1, i.e., any one of SEQ ID NOs: 1-276. In certain embodiments, the first strand of the nucleic acid according to the invention comprises a contiguous nucleoside sequence of 19 nucleosides, wherein at least 14, 15, 16, 17, 18 or all 19 nucleosides of said contiguous nucleoside sequence are complementary to a contiguous portion of any one of the sequences listed in Table 1, i.e., any one of SEQ ID NOs: 1- 276. In certain embodiments, the first strand of the nucleic acid according to the invention comprises a contiguous nucleoside sequence of 23 nucleosides, wherein at least 18, 19, 20, 21, 22 or all 23 nucleosides of said contiguous nucleoside sequence are complementary to a contiguous portion of any one of the sequences listed in Table 1, i.e., any one of SEQ ID NOs: 1- 276. In some embodiments, a nucleic acid e.g. an siRNA of the invention includes a sense strand that is substantially or partially complementary to an antisense oligonucleoside which, in turn, is complementary to a target gene sequence and comprises a contiguous nucleoside sequence. The nucleoside sequence of the sense strand is typically at least about 80% complementary over its entire length to the equivalent region of the nucleoside sequence of the antisense strand, such as about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% complementary, or 100% complementary. In some embodiments, a nucleic acid e.g. an siRNA of the invention includes an antisense strand that is substantially or partially complementary to the target sequence and comprises a contiguous nucleoside sequence which is at least 80% complementary over its entire length to the target sequence such as about 85%, 86%, 87%, 88%, 89%, 90%, 91 %, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% complementary, or 100% complementary. As used herein, a "subject" is an animal, such as a mammal, including a primate (such as a human, a non-human primate, e.g., a monkey, and a chimpanzee), or a non-primate or a bird that expresses the target gene, either endogenously or heterologously, when the target gene sequence has sufficient complementarity to the nucleic acid e.g. iRNA agent to promote target knockdown. In certain preferred embodiments, the subject is a human. The terms "treating" or "treatment" refer to a beneficial or desired result including, but not limited to, alleviation or amelioration of one or more symptoms associated with gene expression. "Treatment" can also mean prolonging survival as compared to expected survival in the absence of treatment. The terms “prevent” or “prevention” as used herein are defined as eliminating or reducing the likelihood of occurrence of one or more symptoms of a disease or disorder. For example, the inhibitor disclosed herein can be used to prevent the occurrence of a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis. "Therapeutically effective amount," as used herein, is intended to include the amount of a nucleic acid e.g. an iRNA that, when administered to a patient for treating a subject having disease, is sufficient to effect treatment of the disease (e.g., by diminishing, ameliorating or maintaining the existing disease or one or more symptoms of disease or its related comorbidities). The phrase "pharmaceutically acceptable" is employed herein to refer to compounds, materials, compositions, or dosage forms which are suitable for use in contact with the tissues of human subjects and animal subjects without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. The phrase "pharmaceutically-acceptable carrier" as used herein means a pharmaceutically- acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid or solvent encapsulating material, involved in carrying or transporting the subject compound from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the subject being treated. Where a value or range of values of a parameter are recited, it is intended that values and ranges intermediate to the recited values are also intended to be part of this invention. The articles "a" and "an" are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. The term "including" is used herein to mean, and is used interchangeably with, the phrase "including but not limited to". The term "or" is used herein to mean, and is used interchangeably with, the term "and/or," unless context clearly indicates otherwise. For example, "sense strand or antisense strand" is understood as "sense strand or antisense strand or sense strand and antisense strand." The term "about" is used herein to mean within the typical ranges of tolerances in the art. For example, "about" can be understood as about 2 standard deviations from the mean. In certain embodiments, about means +10%. In certain embodiments, about means +5%. When about is present before a series of numbers or a range, it is understood that "about" can modify each of the numbers in the series or range. The term "at least" prior to a number or series of numbers is understood to include the number adjacent to the term "at least", and all subsequent numbers or integers that could logically be included, as clear from context. For example, the number of nucleotides in a nucleic acid molecule must be an integer. For example, "at least 18 nucleosides of a 21 nucleoside nucleic acid molecule" means that 18, 19, 20, or 21 nucleosides have the indicated property. When at least is present before a series of numbers or a range, it is understood that "at least" can modify each of the numbers in the series or range. As used herein, "no more than" or "less than" is understood as the value adjacent to the phrase and logical lower values or integers, as logical from context, to zero. For example, a duplex with an overhang of "no more than 2 nucleosides" has a 2, 1, or 0 nucleoside overhang. When "no more than" is present before a series of numbers or a range, it is understood that "no more than" can modify each of the numbers in the series or range. The terminal region of a strand is the last 5 nucleotides from the 5’ or the 3’ end. A nucleobase sequence is the sequence of the bases of the nucleic acid in an oligomer. Various embodiments of the invention can be combined as determined appropriate by one of skill in the art. TARGET A target for inhibition disclosed herein may be, without limitation, an mRNA, polypeptide, protein, or gene. These targets are a target the inhibition of which helps in the prevention and/or treatment of a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or in reducing adipogenesis. The target for inhibition is the gene SLC25A5 or a gene product thereof, such as an mRNA transcribed from the SLC25A5 gene or the ANT2 protein, and inhibition may be effected by inhibition of expression or function of the SLC25A5/ANT2 gene or protein or both. In a preferred embodiment, the target is an mRNA expressed from the SLC25A5 gene. Exemplary target sequences on the SLC25A5 mRNA are listed below in Table 1. Following Table 1 provides oligonucleoside mRNA target sequences of SLC25A5, together with the corresponding positions in transcript ENST00000317881.9. It is to be understood that SEQ ID NO: 1 to 276 refer to human (Homo sapiens) mRNA sequences. Table 1 SEQ ID NO Oligonucleotide mRNA target sequence Starting position on 5’ ^ 3’ ENST00000317881.9 SEQ ID NO: 1 ACUAUUUACUGGUUGAAAAUGGG 1072 SEQ ID NO: 2 UACAAAGGCAUUAUAGACUGCGU 223 SEQ ID NO: 3 UAUGAUGAAAUCAAGAAGUACAC 943 SEQ ID NO: 4 AUGAUGAUGGGACUCAAUUGUAU 1146 SEQ ID NO: 5 AGGCAUUAUAGACUGCGUGGUCC 228 SEQ ID NO: 6 CAGUCACUCCUGAUAAAUAACAA 1178 SEQ ID NO: 7 CAAUACAAAGGCAUUAUAGACUG 220 SEQ ID NO: 8 GAGCCGCCUACUUCGGUAUCUAU 635 SEQ ID NO: 9 CGAGCCGCCUACUUCGGUAUCUA 634 SEQ ID NO: 10 AUAGACUGCGUGGUCCGUAUUCC 235 SEQ ID NO: 11 AACACUCACAUCGUCAUCAGCUG 691 SEQ ID NO: 12 UAACUUCGCCUUCAAAGAUAAAU 333 SEQ ID NO: 13 GCCUACUUCGGUAUCUAUGACAC 640 SEQ ID NO: 14 UAUUUACUGGUUGAAAAUGGGAA 1074 SEQ ID NO: 15 UUUGCCCGUACCCGUCUAGCAGC 478 SEQ ID NO: 16 GCAGUCAGGGCGCAAAGGAACUG 792 SEQ ID NO: 17 AUUUACUGGUUGAAAAUGGGAAG 1075 SEQ ID NO: 18 CCGAGCCGCCUACUUCGGUAUCU 633 SEQ ID NO: 19 GGCCUCGGUGACUGCCUGGUUAA 538 SEQ ID NO: 20 CACAUCGUCAUCAGCUGGAUGAU 697 SEQ ID NO: 21 UAUUUCAGUCACUCCUGAUAAAU 1173 SEQ ID NO: 22 GCUGGAUGAUCGCACAGACUGUC 710 SEQ ID NO: 23 AAGCAAUACAAAGGCAUUAUAGA 217 SEQ ID NO: 24 AGGCCUCGGUGACUGCCUGGUUA 537 SEQ ID NO: 25 GGCUUUAACGUGUCUGUGCAGGG 598 SEQ ID NO: 26 ACAAAGGCAUUAUAGACUGCGUG 224 SEQ ID NO: 27 CUGUGAACAGGCAUGUUGUAUUA 993 SEQ ID NO: 28 UCAUCUGACCAGUUUUCUCUUAA 1107 SEQ ID NO: 29 CAAGGCUUUAACGUGUCUGUGCA 595 SEQ ID NO: 30 AUGCAGUCAGGGCGCAAAGGAAC 790 SEQ ID NO: 31 UGGAUGAUCGCACAGACUGUCAC 712 SEQ ID NO: 32 AAAGGCAUUAUAGACUGCGUGGU 226 SEQ ID NO: 33 GAUGAUCGCACAGACUGUCACUG 714 SEQ ID NO: 34 GACUGCGUGGUCCGUAUUCCCAA 238 SEQ ID NO: 35 AGCAAUACAAAGGCAUUAUAGAC 218 SEQ ID NO: 36 GUCAUCAGCUGGAUGAUCGCACA 703 SEQ ID NO: 37 GCAUUAUAGACUGCGUGGUCCGU 230 SEQ ID NO: 38 AUUUUGCCCGUACCCGUCUAGCA 476 SEQ ID NO: 39 UCACAUCGUCAUCAGCUGGAUGA 696 SEQ ID NO: 40 CCUCUUGAUUUUGCCCGUACCCG 469 SEQ ID NO: 41 UUAUAGACUGCGUGGUCCGUAUU 233 SEQ ID NO: 42 GCCGCCUACUUCGGUAUCUAUGA 637 SEQ ID NO: 43 UAGACUGCGUGGUCCGUAUUCCC 236 SEQ ID NO: 44 CGUCAUCAGCUGGAUGAUCGCAC 702 SEQ ID NO: 45 CAUUAUAGACUGCGUGGUCCGUA 231 SEQ ID NO: 46 CGCCUACUUCGGUAUCUAUGACA 639 SEQ ID NO: 47 UUUUAUUUCAGUCACUCCUGAUA 1170 SEQ ID NO: 48 UCGUCAUCAGCUGGAUGAUCGCA 701 SEQ ID NO: 49 UGAUUUUGCCCGUACCCGUCUAG 474 SEQ ID NO: 50 UGCAAAGGGAAUGCUUCCGGAUC 663 SEQ ID NO: 51 CCAAGGCUUUAACGUGUCUGUGC 594 SEQ ID NO: 52 CAAAGGCAUUAUAGACUGCGUGG 225 SEQ ID NO: 53 UCUUGAUUUUGCCCGUACCCGUC 471 SEQ ID NO: 54 ACCGAGCCGCCUACUUCGGUAUC 632 SEQ ID NO: 55 UUAUCAUCUACCGAGCCGCCUAC 623 SEQ ID NO: 56 CUUGAUUUUGCCCGUACCCGUCU 472 SEQ ID NO: 57 AUUAUCAUCUACCGAGCCGCCUA 622 SEQ ID NO: 58 AUCAUCUACCGAGCCGCCUACUU 625 SEQ ID NO: 59 GGCUCUUAACUUCGCCUUCAAAG 327 SEQ ID NO: 60 CCCCACCCAGGCUCUUAACUUCG 318 SEQ ID NO: 61 GUCCGUAUUCCCAAGGAGCAGGG 247 SEQ ID NO: 62 AGGAGCAGGGAGUUCUGUCCUUC 260 SEQ ID NO: 63 AUUCCCAAGGAGCAGGGAGUUCU 253 SEQ ID NO: 64 GGUCCGUAUUCCCAAGGAGCAGG 246 SEQ ID NO: 65 GAGCAGGGAGUUCUGUCCUUCUG 262 SEQ ID NO: 66 UGGUCCGUAUUCCCAAGGAGCAG 245 SEQ ID NO: 67 GGAGCAGGGAGUUCUGUCCUUCU 261 SEQ ID NO: 68 AAGGAGCAGGGAGUUCUGUCCUU 259 SEQ ID NO: 69 UAUUCCCAAGGAGCAGGGAGUUC 252 SEQ ID NO: 70 CAAGGAGCAGGGAGUUCUGUCCU 258 SEQ ID NO: 71 UCCCCACCCAGGCUCUUAACUUC 317 SEQ ID NO: 72 GCUCUUAACUUCGCCUUCAAAGA 328 SEQ ID NO: 73 AUUUCAGUCACUCCUGAUAAAUA 1174 SEQ ID NO: 74 UUCAGUCACUCCUGAUAAAUAAC 1176 SEQ ID NO: 75 UUUCAGUCACUCCUGAUAAAUAA 1175 SEQ ID NO: 76 GAUGAUGGGACUCAAUUGUAUUU 1148 SEQ ID NO: 77 AUGAUGGGACUCAAUUGUAUUUU 1149 SEQ ID NO: 78 GUCACUCCUGAUAAAUAACAAAU 1180 SEQ ID NO: 79 AUAUUCAUCUGACCAGUUUUCUC 1103 SEQ ID NO: 80 UGAACAGGCAUGUUGUAUUAUAU 996 SEQ ID NO: 81 AAAGGGAAUGCUUCCGGAUCCCA 666 SEQ ID NO: 82 AAGGGAAUGCUUCCGGAUCCCAA 667 SEQ ID NO: 83 UCCGAGGCCUCGGUGACUGCCUG 533 SEQ ID NO: 84 GAACAGGCAUGUUGUAUUAUAUA 997 SEQ ID NO: 85 GCAAUACAAAGGCAUUAUAGACU 219 SEQ ID NO: 86 UUAUUUCAGUCACUCCUGAUAAA 1172 SEQ ID NO: 87 UGAUGAUGGGACUCAAUUGUAUU 1147 SEQ ID NO: 88 AUCUGACCAGUUUUCUCUUAAAG 1109 SEQ ID NO: 89 UCUGACCAGUUUUCUCUUAAAGC 1110 SEQ ID NO: 90 CAGAUAAGCAAUACAAAGGCAUU 212 SEQ ID NO: 91 AGAUAAGCAAUACAAAGGCAUUA 213 SEQ ID NO: 92 CUUUAACGUGUCUGUGCAGGGUA 600 SEQ ID NO: 93 UUUAACGUGUCUGUGCAGGGUAU 601 SEQ ID NO: 94 ACUCACAUCGUCAUCAGCUGGAU 694 SEQ ID NO: 95 GAUGAUGAUGGGACUCAAUUGUA 1145 SEQ ID NO: 96 AGACUGCGUGGUCCGUAUUCCCA 237 SEQ ID NO: 97 GUGAACAGGCAUGUUGUAUUAUA 995 SEQ ID NO: 98 UUUAUUUCAGUCACUCCUGAUAA 1171 SEQ ID NO: 99 GAUAAGCAAUACAAAGGCAUUAU 214 SEQ ID NO: 100 ACACUCACAUCGUCAUCAGCUGG 692 SEQ ID NO: 101 AGCCGCCUACUUCGGUAUCUAUG 636 SEQ ID NO: 102 CUCACAUCGUCAUCAGCUGGAUG 695 SEQ ID NO: 103 CCGCCUACUUCGGUAUCUAUGAC 638 SEQ ID NO: 104 GCUUUAACGUGUCUGUGCAGGGU 599 SEQ ID NO: 105 GUUCGCCGCCGCAUGAUGAUGCA 772 SEQ ID NO: 106 GGCAUUAUAGACUGCGUGGUCCG 229 SEQ ID NO: 107 ACUGCGUGGUCCGUAUUCCCAAG 239 SEQ ID NO: 108 UCAUCUACCGAGCCGCCUACUUC 626 SEQ ID NO: 109 UUUUGCCCGUACCCGUCUAGCAG 477 SEQ ID NO: 110 CACUCACAUCGUCAUCAGCUGGA 693 SEQ ID NO: 111 AUUAUAGACUGCGUGGUCCGUAU 232 SEQ ID NO: 112 GAGGCCUCGGUGACUGCCUGGUU 536 SEQ ID NO: 113 CUGGAUGAUCGCACAGACUGUCA 711 SEQ ID NO: 114 UUGAUUUUGCCCGUACCCGUCUA 473 SEQ ID NO: 115 AUGAUCGCACAGACUGUCACUGC 715 SEQ ID NO: 116 GGAUGAUCGCACAGACUGUCACU 713 SEQ ID NO: 117 GAUUUUGCCCGUACCCGUCUAGC 475 SEQ ID NO: 118 UAUCAUCUACCGAGCCGCCUACU 624 SEQ ID NO: 119 UAUAGACUGCGUGGUCCGUAUUC 234 SEQ ID NO: 120 CACUGCAGAUAAGCAAUACAAAG 207 SEQ ID NO: 121 UCACUGCAGAUAAGCAAUACAAA 206 SEQ ID NO: 122 AUCACUGCAGAUAAGCAAUACAA 205 SEQ ID NO: 123 CAGCAAGCAGAUCACUGCAGAUA 195 SEQ ID NO: 124 AGAUCACUGCAGAUAAGCAAUAC 203 SEQ ID NO: 125 GAUCACUGCAGAUAAGCAAUACA 204 SEQ ID NO: 126 AAGCAGAUCACUGCAGAUAAGCA 199 SEQ ID NO: 127 AGCAGAUCACUGCAGAUAAGCAA 200 SEQ ID NO: 128 CCAGCAAGCAGAUCACUGCAGAU 194 SEQ ID NO: 129 CAGAUCACUGCAGAUAAGCAAUA 202 SEQ ID NO: 130 UGAUAAAUAACAAAUUUGGAGAA 1188 SEQ ID NO: 131 ACUCCUGAUAAAUAACAAAUUUG 1183 SEQ ID NO: 132 CUGAAAGGGAAUUCCGAGGCCUC 521 SEQ ID NO: 133 AUGUUGUAUUAUAUAACAUAUCU 1005 SEQ ID NO: 134 AAUUCCGAGGCCUCGGUGACUGC 530 SEQ ID NO: 135 UGAAAGGGAAUUCCGAGGCCUCG 522 SEQ ID NO: 136 GUUGUAUUAUAUAACAUAUCUUG 1007 SEQ ID NO: 137 GGAAUUCCGAGGCCUCGGUGACU 528 SEQ ID NO: 138 AAGGGAAUUCCGAGGCCUCGGUG 525 SEQ ID NO: 139 GGAGCUGAAAGGGAAUUCCGAGG 517 SEQ ID NO: 140 CUGGAGCUGAAAGGGAAUUCCGA 515 SEQ ID NO: 141 AGCUGAAAGGGAAUUCCGAGGCC 519 SEQ ID NO: 142 UGGAGCUGAAAGGGAAUUCCGAG 516 SEQ ID NO: 143 GAGCUGAAAGGGAAUUCCGAGGC 518 SEQ ID NO: 144 AGGCAUGUUGUAUUAUAUAACAU 1001 SEQ ID NO: 145 UGUUGUAUUAUAUAACAUAUCUU 1006 SEQ ID NO: 146 UUGUAUUAUAUAACAUAUCUUGA 1008 SEQ ID NO: 147 CAGGCAUGUUGUAUUAUAUAACA 1000 SEQ ID NO: 148 GAAAGGGAAUUCCGAGGCCUCGG 523 SEQ ID NO: 149 GGGAAUUCCGAGGCCUCGGUGAC 527 SEQ ID NO: 150 AAAGGGAAUUCCGAGGCCUCGGU 524 SEQ ID NO: 151 AGGGAAUUCCGAGGCCUCGGUGA 526 SEQ ID NO: 152 GUGCUUGUCUUGUAUGAUGAAAU 931 SEQ ID NO: 153 CUUCGCCUUCAAAGAUAAAUACA 336 SEQ ID NO: 154 CUGCCUGGUUAAGAUCUACAAAU 549 SEQ ID NO: 155 UAUCUAUGACACUGCAAAGGGAA 651 SEQ ID NO: 156 CUUUUGUGCUUGUCUUGUAUGAU 926 SEQ ID NO: 157 GGUGACUGCCUGGUUAAGAUCUA 544 SEQ ID NO: 158 AUGACACUGCAAAGGGAAUGCUU 656 SEQ ID NO: 159 UUCGGUAUCUAUGACACUGCAAA 646 SEQ ID NO: 160 UAUUCAUCUGACCAGUUUUCUCU 1104 SEQ ID NO: 161 ACUUCGGUAUCUAUGACACUGCA 644 SEQ ID NO: 162 CUGGUUAAGAUCUACAAAUCUGA 553 SEQ ID NO: 163 GUAUCUAUGACACUGCAAAGGGA 650 SEQ ID NO: 164 CAAGGGUGCAUGGUCCAAUGUUC 885 SEQ ID NO: 165 AGAUCUACAAAUCUGAUGGGAUU 560 SEQ ID NO: 166 UACUUCGGUAUCUAUGACACUGC 643 SEQ ID NO: 167 CAUGGGUGGUGCUUUUGUGCUUG 915 SEQ ID NO: 168 GGUAUUAUCAUCUACCGAGCCGC 619 SEQ ID NO: 169 GCGUGGUCCGUAUUCCCAAGGAG 242 SEQ ID NO: 170 AUCUAUGACACUGCAAAGGGAAU 652 SEQ ID NO: 171 UGCUUUUGUGCUUGUCUUGUAUG 924 SEQ ID NO: 172 UGUACCAAGGCUUUAACGUGUCU 590 SEQ ID NO: 173 GGGUGCAUGGUCCAAUGUUCUCA 888 SEQ ID NO: 174 CGCCUUCAAAGAUAAAUACAAGC 339 SEQ ID NO: 175 CAGGGUAUUAUCAUCUACCGAGC 616 SEQ ID NO: 176 CCUACUUCGGUAUCUAUGACACU 641 SEQ ID NO: 177 UGGUUAAGAUCUACAAAUCUGAU 554 SEQ ID NO: 178 UGUGCAGGGUAUUAUCAUCUACC 612 SEQ ID NO: 179 AAUCUGAUGGGAUUAAGGGCCUG 569 SEQ ID NO: 180 GUCUGUGCAGGGUAUUAUCAUCU 609 SEQ ID NO: 181 UCUGAUGGGAUUAAGGGCCUGUA 571 SEQ ID NO: 182 UACCAAGGCUUUAACGUGUCUGU 592 SEQ ID NO: 183 AAUAUUCAUCUGACCAGUUUUCU 1102 SEQ ID NO: 184 UGACUGCCUGGUUAAGAUCUACA 546 SEQ ID NO: 185 GGGUUGACUUCCUAUCCAUUUGA 745 SEQ ID NO: 186 UCUAUGACACUGCAAAGGGAAUG 653 SEQ ID NO: 187 GGUUAAGAUCUACAAAUCUGAUG 555 SEQ ID NO: 188 GCAGGGUAUUAUCAUCUACCGAG 615 SEQ ID NO: 189 ACUGCCUGGUUAAGAUCUACAAA 548 SEQ ID NO: 190 AUCUGAUGGGAUUAAGGGCCUGU 570 SEQ ID NO: 191 UCGGUAUCUAUGACACUGCAAAG 647 SEQ ID NO: 192 GUACCCGUCUAGCAGCUGAUGUG 485 SEQ ID NO: 193 GGUAUCUAUGACACUGCAAAGGG 649 SEQ ID NO: 194 AGCUGAUGUGGGUAAAGCUGGAG 498 SEQ ID NO: 195 CGUCUAGCAGCUGAUGUGGGUAA 490 SEQ ID NO: 196 AAGGGCCUGUACCAAGGCUUUAA 583 SEQ ID NO: 197 UGCCCGUACCCGUCUAGCAGCUG 480 SEQ ID NO: 198 AGCAGCUGAUGUGGGUAAAGCUG 495 SEQ ID NO: 199 GCCCGUACCCGUCUAGCAGCUGA 481 SEQ ID NO: 200 CAGCUGAUGUGGGUAAAGCUGGA 497 SEQ ID NO: 201 AGGGUAUUAUCAUCUACCGAGCC 617 SEQ ID NO: 202 UAUUAUCAUCUACCGAGCCGCCU 621 SEQ ID NO: 203 CCGUACCCGUCUAGCAGCUGAUG 483 SEQ ID NO: 204 CUGAUGGGAUUAAGGGCCUGUAC 572 SEQ ID NO: 205 GUGUCUGUGCAGGGUAUUAUCAU 607 SEQ ID NO: 206 CUGCGUGGUCCGUAUUCCCAAGG 240 SEQ ID NO: 207 UGCGUGGUCCGUAUUCCCAAGGA 241 SEQ ID NO: 208 CCUGGUUAAGAUCUACAAAUCUG 552 SEQ ID NO: 209 GUAUGAUGAAAUCAAGAAGUACA 942 SEQ ID NO: 210 AAGAUCUACAAAUCUGAUGGGAU 559 SEQ ID NO: 211 CUGUGCAGGGUAUUAUCAUCUAC 611 SEQ ID NO: 212 CUGUACCAAGGCUUUAACGUGUC 589 SEQ ID NO: 213 UAGCAGCUGAUGUGGGUAAAGCU 494 SEQ ID NO: 214 GCAUGGGUGGUGCUUUUGUGCUU 914 SEQ ID NO: 215 CUCGGUGACUGCCUGGUUAAGAU 541 SEQ ID NO: 216 GUCUAGCAGCUGAUGUGGGUAAA 491 SEQ ID NO: 217 UCUACAAAUCUGAUGGGAUUAAG 563 SEQ ID NO: 218 CUACUUCGGUAUCUAUGACACUG 642 SEQ ID NO: 219 GCAGCUGAUGUGGGUAAAGCUGG 496 SEQ ID NO: 220 CCCGUACCCGUCUAGCAGCUGAU 482 SEQ ID NO: 221 UGUCUGUGCAGGGUAUUAUCAUC 608 SEQ ID NO: 222 UGUGCUUGUCUUGUAUGAUGAAA 930 SEQ ID NO: 223 GUACCAAGGCUUUAACGUGUCUG 591 SEQ ID NO: 224 AAGGGUGCAUGGUCCAAUGUUCU 886 SEQ ID NO: 225 GUGACUGCCUGGUUAAGAUCUAC 545 SEQ ID NO: 226 CUGAUGUGGGUAAAGCUGGAGCU 500 SEQ ID NO: 227 CGUGGUCCGUAUUCCCAAGGAGC 243 SEQ ID NO: 228 UGACACUGCAAAGGGAAUGCUUC 657 SEQ ID NO: 229 GGGAUUAAGGGCCUGUACCAAGG 577 SEQ ID NO: 230 UCUGUGCAGGGUAUUAUCAUCUA 610 SEQ ID NO: 231 UUAACGUGUCUGUGCAGGGUAUU 602 SEQ ID NO: 232 AGGGCCUGUACCAAGGCUUUAAC 584 SEQ ID NO: 233 UAUGACACUGCAAAGGGAAUGCU 655 SEQ ID NO: 234 CCUCGGUGACUGCCUGGUUAAGA 540 SEQ ID NO: 235 GUGCUUUUGUGCUUGUCUUGUAU 923 SEQ ID NO: 236 UGGGUGGUGCUUUUGUGCUUGUC 917 SEQ ID NO: 237 CCCGUCUAGCAGCUGAUGUGGGU 488 SEQ ID NO: 238 UAAGGGCCUGUACCAAGGCUUUA 582 SEQ ID NO: 239 UUGUGCUUGUCUUGUAUGAUGAA 929 SEQ ID NO: 240 ACAAAUCUGAUGGGAUUAAGGGC 566 SEQ ID NO: 241 AUCUACAAAUCUGAUGGGAUUAA 562 SEQ ID NO: 242 UGCAGGGUAUUAUCAUCUACCGA 614 SEQ ID NO: 243 GCCUGUACCAAGGCUUUAACGUG 587 SEQ ID NO: 244 UAAGAUCUACAAAUCUGAUGGGA 558 SEQ ID NO: 245 GCUUUUGUGCUUGUCUUGUAUGA 925 SEQ ID NO: 246 CUACAAAUCUGAUGGGAUUAAGG 564 SEQ ID NO: 247 UUCAAGGGUGCAUGGUCCAAUGU 883 SEQ ID NO: 248 UGGGAUUAAGGGCCUGUACCAAG 576 SEQ ID NO: 249 CUUCGGUAUCUAUGACACUGCAA 645 SEQ ID NO: 250 ACCAAGGCUUUAACGUGUCUGUG 593 SEQ ID NO: 251 GGCAUGGGUGGUGCUUUUGUGCU 913 SEQ ID NO: 252 GUUAAGAUCUACAAAUCUGAUGG 556 SEQ ID NO: 253 UACCCGUCUAGCAGCUGAUGUGG 486 SEQ ID NO: 254 CUAUGACACUGCAAAGGGAAUGC 654 SEQ ID NO: 255 UCUAGCAGCUGAUGUGGGUAAAG 492 SEQ ID NO: 256 CUGCAAAGGGAAUGCUUCCGGAU 662 SEQ ID NO: 257 UUGCCCGUACCCGUCUAGCAGCU 479 SEQ ID NO: 258 GGGUAUUAUCAUCUACCGAGCCG 618 SEQ ID NO: 259 CCCUCUUGAUUUUGCCCGUACCC 468 SEQ ID NO: 260 CGUACCCGUCUAGCAGCUGAUGU 484 SEQ ID NO: 261 UACAAAUCUGAUGGGAUUAAGGG 565 SEQ ID NO: 262 GUGUACCCUCUUGAUUUUGCCCG 463 SEQ ID NO: 263 GGCCUGUACCAAGGCUUUAACGU 586 SEQ ID NO: 264 GAUGGGAUUAAGGGCCUGUACCA 574 SEQ ID NO: 265 GUAUUAUCAUCUACCGAGCCGCC 620 SEQ ID NO: 266 GGGCCUGUACCAAGGCUUUAACG 585 SEQ ID NO: 267 UGAUGGGAUUAAGGGCCUGUACC 573 SEQ ID NO: 268 UAACGUGUCUGUGCAGGGUAUUA 603 SEQ ID NO: 269 AAGGCAUUAUAGACUGCGUGGUC 227 SEQ ID NO: 270 ACUUCCCCACCCAGGCUCUUAAC 314 SEQ ID NO: 271 CAAUGUCAUCAGAUACUUCCCCA 300 SEQ ID NO: 272 AUGUCAUCAGAUACUUCCCCACC 302 SEQ ID NO: 273 AAUGUCAUCAGAUACUUCCCCAC 301 SEQ ID NO: 274 CCAAUGUCAUCAGAUACUUCCCC 299 SEQ ID NO: 275 UACUUCCCCACCCAGGCUCUUAA 313 SEQ ID NO: 276 AUCUACCGAGCCGCCUACUUCGG 628 It is to be understood that SEQ ID NOs: 1 to 276 relate to human (Homo sapiens) mRNA sequences. DISEASE/CONDITIONS The present invention further provides methods of treatment of a subject in need thereof. The treatment methods of the invention include administering a nucleic acid such as an siRNA of the invention to a subject, e.g., a subject that would benefit from a reduction or inhibition of the expression of SLC25A5 gene, in a therapeutically effective amount e.g. a nucleic acid such as an siRNA targeting SLC25A5 or a pharmaceutical composition comprising the nucleic acid targeting SLC25A5. The disease to be treated is related to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or adipogenesis. The disease to be treated is related to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or adipogenesis. The inhibitor according to the invention may be used in the prevention and/or treatment of a metabolic disease or disorder. As used herein, the term "metabolic disease" refers to a disease or condition affecting a metabolic process in a subject and is often caused by disruption of normal metabolism. The patient to be treated may be a patient that already has a metabolic disease or disorder or that is at risk of developing a metabolic disease or disorder. That is, in certain embodiments, the inhibitor of the present invention may be used in the treatment and/or management of an existing metabolic disease or disorder. Treatment and/or management of an existing metabolic disease or disorder with the inhibitor of the present invention may prevent worsening of the metabolic disease or disorder and/or reverse the metabolic disease or disorder. In some instances, treatment of an existing metabolic disease or disorder with the inhibitor of the present invention may even cure the metabolic disease or disorder. In certain embodiments, the inhibitor of the present invention may be used to prevent manifestation of a metabolic disease or disorder in a patient that is at risk of developing a metabolic disease or disorder. The skilled person is capable of diagnosing whether a patient has a metabolic disease or disorder or is at risk of developing a metabolic disease or disorder. For example, a metabolic disease or disorder may be diagnosed based weight gain and/or one or more blood markers, including, without limitation, blood glucose levels, blood insulin levels, blood free fatty acid levels, blood HbA1c levels, blood fibrinogen levels, blood cholesterol levels and blood triglyceride levels. The skilled person is aware of threshold values of one or more blood markers that indicate the presence of a metabolic disease or disorder or the risk of developing a metabolic disease or disorder. In certain embodiments, the metabolic disease is fatty liver disease, in particular non-alcoholic fatty liver disease (NAFLD). As used herein “fatty-liver disease” refers to a disease wherein fat is excessively accumulated in the liver and can cause severe diseases such as chronic hepatitis and hepatic cirrhosis. In patients with fatty liver disease, lipids, particularly neutral fat, accumulate in hepatocytes to the extent that the amount exceeds the physiologically permissible range. From a biochemical point of view, a standard for judgment of fatty liver is that the weight of neutral fat is about 10% (100 mg/g wet weight) or more of the wet weight of hepatic tissue. Fatty liver disease is generally detected by observation of elevated serum levels of liver-specific enzymes such as the transaminases ALT and AST, which serve as indices of hepatocyte injury, as well as by presentation of symptoms, which include fatigue and pain in the region of the liver, though definitive diagnosis often requires a biopsy and may be supported by imaging such as ultrasound and/or MRI. The term “NAFLD” or “non-alcoholic fatty liver disease”, as used herein, relates to a condition occurring when fat is deposited in the liver (steatosis) not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome. In a preferred embodiment, the fatty liver disease is Non-Alcoholic SteatoHepatitis (NASH). NASH, as used herein, refers to a liver disease characterized by an accumulation of fat (lipid droplets), along with inflammation and degeneration of hepatocytes. Once initiated, the disease is accompanied with a high risk of cirrhosis, a state wherein liver functions are altered that can progress to liver insufficiency. Thereafter, NASH often progresses to liver cancer. In certain embodiments, the invention relates to the inhibitor according to the invention for use in reducing one or more of steatosis, lobular inflammation, and/or hepatocytic ballooning. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a disease or disorder associated with increased steatosis, increased lobular inflammation, and/or increased hepatocytic ballooning. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment and/or prevention of fatty liver disease, such as NAFLD or NASH, wherein the inhibitor according to the invention results in one or more of: reduced steatosis, reduced lobular inflammation, and/or reduced hepatocytic ballooning. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment and/or prevention of liver steatosis. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment and/or prevention of lobular inflammation of the liver. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment and/or prevention of hepatocytic ballooning of the liver. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment or prevention of liver fibrosis in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a disease or disorder associated with liver fibrosis. In certain embodiments, the invention relates to the inhibitor according to the invention for use in the treatment and/or prevention of fatty liver disease, such as NAFLD or NASH, wherein the inhibitor according to the invention reduces fibrosis stage. The person skilled in the art is aware of method to determine the level of liver steatosis, lobular inflammation, hepatocytic ballooning or fibrosis stage in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in reducing the levels of one or more of Alanine transaminase (ALT), Aspartate transaminase (AST), Tissue inhibitor of metalloproteinases-1 (TIMP-1) and/or Type III Procollagen Peptide (PIIINP) in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a disease associated with elevated levels of one or more of Alanine transaminase (ALT), Aspartate transaminase (AST), Tissue inhibitor of metalloproteinases-1 (TIMP-1) and/or Type III Procollagen Peptide (PIIINP) in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a metabolic disease or disorder associated with elevated levels of one or more of Alanine transaminase (ALT), Aspartate transaminase (AST), Tissue inhibitor of metalloproteinases-1 (TIMP-1) and/or Type III Procollagen Peptide (PIIINP) in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a metabolic disease or disorder, wherein the inhibitor according to the invention reduces the levels of one or more of Alanine transaminase (ALT), Aspartate transaminase (AST), Tissue inhibitor of metalloproteinases-1 (TIMP-1) and/or Type III Procollagen Peptide (PIIINP) in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a fatty liver disease, such as NAFLD or NASH, wherein the inhibitor according to the invention reduces the levels of one or more of Alanine transaminase (ALT), Aspartate transaminase (AST), Tissue inhibitor of metalloproteinases-1 (TIMP-1) and/or Type III Procollagen Peptide (PIIINP) in a patient. The skilled person is aware of methods and commercial kits to determine the levels of ALT, AST, TIMP-1 and PIIINP in a patient. In certain In certain embodiments, the invention relates to the inhibitor according to the invention for use in reducing the ratio between liver weight and body weight. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a disease or disorder associated with increased liver weight. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a metabolic disease or disorder associated with increased liver weight. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a metabolic disease or disorder, wherein the inhibitor according to the invention reduces the ratio between liver weight and body weight in a patient. In certain embodiments, the invention relates to the inhibitor according to the invention for use in treating and/or preventing a fatty liver disease, such as NAFLD or NASH, wherein the inhibitor according to the invention reduces the ratio between liver weight and body weight in a patient. In certain embodiments, the metabolic disease is obesity. The term “obesity” as used herein refers to a condition in which the natural energy reserve, stored in the fatty tissue of animals, in particular humans and other mammals, is increased to a point where it is associated with certain health conditions or increased mortality. The term “obese” as used herein is defined for an adult human as having a body mass index (BMI) greater than 30. Obesity is commonly associated with excessive body weight gain, in particular diet-induced body weight gain. "(Diet-induced) body weight gain" is defined herein as body weight gain resulting from an excessive dietary intake, including an excessive dietary intake of fat, in particular saturated fat, and optionally an excessive dietary intake of simple sugars, including sucrose and fructose. For a given subject, an excessive dietary intake, in particular of fat and optionally of simple sugars, refers to the consumption of an amount of diet, in particular of fat and optionally of simple sugars, higher than the amount necessary to meet the physiological needs and maintain the energy balance of said subject. The effect of a treatment on reduction of - or prevention - of diet-induced body weight gain in a subject can be assessed by comparing body weight gain observed in a subject receiving the treatment with those observed in the same subject without treatment receiving the same diet and having the same level of physical activity. In certain embodiments, a patient is at risk of developing obesity if the patient has a BMI greater than 25. In certain embodiments, a patient is obese if the patient has a BMI greater than 30. The term “body mass index” as used herein means the ratio of weight in kg divided by the height in metres, squared. A “disease associated with adipogenesis” refers to a medical condition characterized by the abnormal proliferation and differentiation of adipocytes (fat cells) within the body, leading to an excessive accumulation of adipose tissue. This condition often results in health complications such as obesity, metabolic disorders, and associated comorbidities. Within the present invention, a “reduction of adipogenesis” refers to a medical or pharmaceutical intervention designed to decrease the formation and accumulation of adipocytes within the body. A reduction in adipogenesis may be determined and/or quantified based on the size and/or number of adipocytes in a tissue sample obtained from a patient. Alternatively, or in addition, a reduction in adipogenesis may be determined and/or quantified by gene expression analysis, measurement of adipogenic markers (i.e., by ELISA), assessment of lipid accumulation in a sample and/or measurement of triglyceride levels in cells or tissues. Thus, in a particular embodiment, the invention relates to an inhibitor suitable for use, or for use, in prevention and/or treatment of metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or for use in reducing adipogenesis. INHIBITORS Inhibitors of the invention include nucleic acids such as siRNAs, antibodies and antigen binding fragments thereof, e.g., monoclonal antibodies, polypeptides, antibody–drug conjugates, and small molecules. Preferred are nucleic acids such as siRNA. Certain preferred features of inhibitors of the invention, where these are oligonucelosides such as siRNA, are given below. In certain embodiments, the nucleic acid comprises a first strand comprising a sequence that is at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene (SEQ ID NO:1381). In a preferred embodiment, the nucleic acid comprises a first strand comprising a sequence that is at least partially complementary to an SLC25A5 mRNA. In certain embodiments, the nucleic acid for inhibiting expression of the SLC25A5 gene comprises a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO:277-552. In certain embodiments, the first strand comprises nucleosides 2-18 of any one of the sequences set forth in SEQ ID NO: 277-552. In certain embodiments, the first strand comprises any one of SEQ ID NO: 277-552. In certain embodiments, the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 553-828; wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises any one of SEQ ID NO: 553-828. In certain embodiments, the nucleic acid for inhibiting expression of the SLC25A5 gene comprises a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 21 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 277-552. In certain embodiments, the first strand comprises nucleosides 2-22 of any one of the sequences set forth in SEQ ID NO: 277-552. In certain embodiments, the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO:553-828; wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises any one of SEQ ID NO: 553-828. In certain embodiments, the second strand comprises a nucleoside sequence of at least 19 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 553-828; wherein the second strand has a region of at least 85% complementarity over the 19 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises a nucleoside sequence of at least 21 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 553-828; wherein the second strand has a region of at least 85% complementarity over the 21 contiguous nucleosides to the first strand. In certain embodiments, the nucleic acid comprises a first strand that comprises, consists of, or consists essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of SEQ ID NO: 277-552; and a second strand that comprises, consists of, or consists essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of SEQ ID NO: 553-828. It is preferred herein that the duplex region is formed between a first (antisense) strand and a complementary second (sense) strand. Exemplary pairs of complementary antisense and sense strands are listed in Table 2 below. Table 2 provides the unmodified first (antisense) and corresponding unmodified second (sense) strand sequences for siRNA oligonucleosides according to the present invention, together with the corresponding positions in the overall gene sequence of SEQ ID NO:1381 as follows. Table 2: SEQ ID Antisense Strand Base Sequence SEQ ID Sense Strand Base Sequence Corresponding NO (AS) 5’ ^ 3’ NO (SS) 5’ ^ 3’ positions on (Shown as an Unmodified (Shown as an Unmodified ENST00000317 Nucleotide Sequence) Nucleotide Sequence) 881.9 SEQ ID UUAAGAGAAAACUGGUCAG SEQ ID AUCUGACCAGUUUUCU 1107-1130 NO: 304 AUGA NO: 580 CUUAA SEQ ID UAUCAGGAGUGACUGAAAU SEQ ID UUAUUUCAGUCACUCC 1170-1193 NO: 323 AAAA NO: 599 UGAUA SEQ ID UCCCUUUGCAGUGUCAUAG SEQ ID AUCUAUGACACUGCAA 650-673 NO: 439 AUAC NO: 715 AGGGA SEQ ID AUCAGAUUUGUAGAUCUUA SEQ ID GUUAAGAUCUACAAAU 554-577 NO: 453 ACCA NO: 729 CUGAU SEQ ID AUCAGCUGCUAGACGGGUA SEQ ID CGUACCCGUCUAGCAG 482-505 NO: 496 CGGG NO: 772 CUGAU SEQ ID CCCAUUUUCAACCAGUAAA SEQ ID UAUUUACUGGUUGAAA 1072-1095 NO: 277 UAGU NO: 553 AUGGG SEQ ID ACGCAGUCUAUAAUGCCUU SEQ ID CAAAGGCAUUAUAGAC 223-246 NO: 278 UGUA NO: 554 UGCGU SEQ ID GUGUACUUCUUGAUUUCAU SEQ ID UGAUGAAAUCAAGAAG 943-966 NO: 279 CAUA NO: 555 UACAC SEQ ID AUACAAUUGAGUCCCAUCA SEQ ID GAUGAUGGGACUCAAU 1146-1169 NO: 280 UCAU NO: 556 UGUAU SEQ ID GGACCACGCAGUCUAUAAU SEQ ID GCAUUAUAGACUGCGU 228-251 NO: 281 GCCU NO: 557 GGUCC SEQ ID UUGUUAUUUAUCAGGAGUG SEQ ID GUCACUCCUGAUAAAU 1178-1201 NO: 282 ACUG NO: 558 AACAA SEQ ID CAGUCUAUAAUGCCUUUGU SEQ ID AUACAAAGGCAUUAUA 220-243 NO: 283 AUUG NO: 559 GACUG SEQ ID AUAGAUACCGAAGUAGGCG SEQ ID GCCGCCUACUUCGGUA 635-658 NO: 284 GCUC NO: 560 UCUAU SEQ ID UAGAUACCGAAGUAGGCGG SEQ ID AGCCGCCUACUUCGGU 634-657 NO: 285 CUCG NO: 561 AUCUA SEQ ID GGAAUACGGACCACGCAGU SEQ ID AGACUGCGUGGUCCGU 235-258 NO: 286 CUAU NO: 562 AUUCC SEQ ID CAGCUGAUGACGAUGUGAG SEQ ID CACUCACAUCGUCAUC 691-714 NO: 287 UGUU NO: 563 AGCUG SEQ ID AUUUAUCUUUGAAGGCGAA SEQ ID ACUUCGCCUUCAAAGA 333-356 NO: 288 GUUA NO: 564 UAAAU SEQ ID GUGUCAUAGAUACCGAAGU SEQ ID CUACUUCGGUAUCUAU 640-663 NO: 289 AGGC NO: 565 GACAC SEQ ID UUCCCAUUUUCAACCAGUA SEQ ID UUUACUGGUUGAAAAU 1074-1097 NO: 290 AAUA NO: 566 GGGAA SEQ ID GCUGCUAGACGGGUACGGG SEQ ID UGCCCGUACCCGUCUA 478-501 NO: 291 CAAA NO: 567 GCAGC SEQ ID CAGUUCCUUUGCGCCCUGA SEQ ID AGUCAGGGCGCAAAGG 792-815 NO: 292 CUGC NO: 568 AACUG SEQ ID CUUCCCAUUUUCAACCAGU SEQ ID UUACUGGUUGAAAAUG 1075-1098 NO: 293 AAAU NO: 569 GGAAG SEQ ID AGAUACCGAAGUAGGCGGC SEQ ID GAGCCGCCUACUUCGG 633-656 NO: 294 UCGG NO: 570 UAUCU SEQ ID UUAACCAGGCAGUCACCGA SEQ ID CCUCGGUGACUGCCUG 538-561 NO: 295 GGCC NO: 571 GUUAA SEQ ID AUCAUCCAGCUGAUGACGA SEQ ID CAUCGUCAUCAGCUGG 697-720 NO: 296 UGUG NO: 572 AUGAU SEQ ID AUUUAUCAGGAGUGACUGA SEQ ID UUUCAGUCACUCCUGA 1173-1196 NO: 297 AAUA NO: 573 UAAAU SEQ ID GACAGUCUGUGCGAUCAUC SEQ ID UGGAUGAUCGCACAGA 710-733 NO: 298 CAGC NO: 574 CUGUC SEQ ID UCUAUAAUGCCUUUGUAUU SEQ ID GCAAUACAAAGGCAUU 217-240 NO: 299 GCUU NO: 575 AUAGA SEQ ID UAACCAGGCAGUCACCGAG SEQ ID GCCUCGGUGACUGCCU 537-560 NO: 300 GCCU NO: 576 GGUUA SEQ ID CCCUGCACAGACACGUUAA SEQ ID CUUUAACGUGUCUGUG 598-621 NO: 301 AGCC NO: 577 CAGGG SEQ ID CACGCAGUCUAUAAUGCCU SEQ ID AAAGGCAUUAUAGACU 224-247 NO: 302 UUGU NO: 578 GCGUG SEQ ID UAAUACAACAUGCCUGUUC SEQ ID GUGAACAGGCAUGUUG 993-1016 NO: 303 ACAG NO: 579 UAUUA SEQ ID UGCACAGACACGUUAAAGC SEQ ID AGGCUUUAACGUGUCU 595-618 NO: 305 CUUG NO: 581 GUGCA SEQ ID GUUCCUUUGCGCCCUGACU SEQ ID GCAGUCAGGGCGCAAA 790-813 NO: 306 GCAU NO: 582 GGAAC SEQ ID GUGACAGUCUGUGCGAUCA SEQ ID GAUGAUCGCACAGACU 712-735 NO: 307 UCCA NO: 583 GUCAC SEQ ID ACCACGCAGUCUAUAAUGC SEQ ID AGGCAUUAUAGACUGC 226-249 NO: 308 CUUU NO: 584 GUGGU SEQ ID CAGUGACAGUCUGUGCGAU SEQ ID UGAUCGCACAGACUGU 714-737 NO: 309 CAUC NO: 585 CACUG SEQ ID UUGGGAAUACGGACCACGC SEQ ID CUGCGUGGUCCGUAUU 238-261 NO: 310 AGUC NO: 586 CCCAA SEQ ID GUCUAUAAUGCCUUUGUAU SEQ ID CAAUACAAAGGCAUUA 218-241 NO: 311 UGCU NO: 587 UAGAC SEQ ID UGUGCGAUCAUCCAGCUGA SEQ ID CAUCAGCUGGAUGAUC 703-726 NO: 312 UGAC NO: 588 GCACA SEQ ID ACGGACCACGCAGUCUAUA SEQ ID AUUAUAGACUGCGUGG 230-253 NO: 313 AUGC NO: 589 UCCGU SEQ ID UGCUAGACGGGUACGGGCA SEQ ID UUUGCCCGUACCCGUC 476-499 NO: 314 AAAU NO: 590 UAGCA SEQ ID UCAUCCAGCUGAUGACGAU SEQ ID ACAUCGUCAUCAGCUG 696-719 NO: 315 GUGA NO: 591 GAUGA SEQ ID CGGGUACGGGCAAAAUCAA SEQ ID UCUUGAUUUUGCCCGU 469-492 NO: 316 GAGG NO: 592 ACCCG SEQ ID AAUACGGACCACGCAGUCU SEQ ID AUAGACUGCGUGGUCC 233-256 NO: 317 AUAA NO: 593 GUAUU SEQ ID UCAUAGAUACCGAAGUAGG SEQ ID CGCCUACUUCGGUAUC 637-660 NO: 318 CGGC NO: 594 UAUGA SEQ ID GGGAAUACGGACCACGCAG SEQ ID GACUGCGUGGUCCGUA 236-259 NO: 319 UCUA NO: 595 UUCCC SEQ ID GUGCGAUCAUCCAGCUGAU SEQ ID UCAUCAGCUGGAUGAU 702-725 NO: 320 GACG NO: 596 CGCAC SEQ ID UACGGACCACGCAGUCUAU SEQ ID UUAUAGACUGCGUGGU 231-254 NO: 321 AAUG NO: 597 CCGUA SEQ ID UGUCAUAGAUACCGAAGUA SEQ ID CCUACUUCGGUAUCUA 639-662 NO: 322 GGCG NO: 598 UGACA SEQ ID UGCGAUCAUCCAGCUGAUG SEQ ID GUCAUCAGCUGGAUGA 701-724 NO: 324 ACGA NO: 600 UCGCA SEQ ID CUAGACGGGUACGGGCAAA SEQ ID AUUUUGCCCGUACCCG 474-497 NO: 325 AUCA NO: 601 UCUAG SEQ ID GAUCCGGAAGCAUUCCCUU SEQ ID CAAAGGGAAUGCUUCC 663-686 NO: 326 UGCA NO: 602 GGAUC SEQ ID GCACAGACACGUUAAAGCC SEQ ID AAGGCUUUAACGUGUC 594-617 NO: 327 UUGG NO: 603 UGUGC SEQ ID CCACGCAGUCUAUAAUGCC SEQ ID AAGGCAUUAUAGACUG 225-248 NO: 328 UUUG NO: 604 CGUGG SEQ ID GACGGGUACGGGCAAAAUC SEQ ID UUGAUUUUGCCCGUAC 471-494 NO: 329 AAGA NO: 605 CCGUC SEQ ID GAUACCGAAGUAGGCGGCU SEQ ID CGAGCCGCCUACUUCG 632-655 NO: 330 CGGU NO: 606 GUAUC SEQ ID GUAGGCGGCUCGGUAGAUG SEQ ID AUCAUCUACCGAGCCG 623-646 NO: 331 AUAA NO: 607 CCUAC SEQ ID AGACGGGUACGGGCAAAAU SEQ ID UGAUUUUGCCCGUACC 472-495 NO: 332 CAAG NO: 608 CGUCU SEQ ID UAGGCGGCUCGGUAGAUGA SEQ ID UAUCAUCUACCGAGCC 622-645 NO: 333 UAAU NO: 609 GCCUA SEQ ID AAGUAGGCGGCUCGGUAGA SEQ ID CAUCUACCGAGCCGCC 625-648 NO: 334 UGAU NO: 610 UACUU SEQ ID CUUUGAAGGCGAAGUUAAG SEQ ID CUCUUAACUUCGCCUU 327-350 NO: 335 AGCC NO: 611 CAAAG SEQ ID CGAAGUUAAGAGCCUGGGU SEQ ID CCACCCAGGCUCUUAA 318-341 NO: 336 GGGG NO: 612 CUUCG SEQ ID CCCUGCUCCUUGGGAAUAC SEQ ID CCGUAUUCCCAAGGAG 247-270 NO: 337 GGAC NO: 613 CAGGG SEQ ID GAAGGACAGAACUCCCUGC SEQ ID GAGCAGGGAGUUCUGU 260-283 NO: 338 UCCU NO: 614 CCUUC SEQ ID AGAACUCCCUGCUCCUUGG SEQ ID UCCCAAGGAGCAGGGA 253-276 NO: 339 GAAU NO: 615 GUUCU SEQ ID CCUGCUCCUUGGGAAUACG SEQ ID UCCGUAUUCCCAAGGA 246-269 NO: 340 GACC NO: 616 GCAGG SEQ ID CAGAAGGACAGAACUCCCU SEQ ID GCAGGGAGUUCUGUCC 262-285 NO: 341 GCUC NO: 617 UUCUG SEQ ID CUGCUCCUUGGGAAUACGG SEQ ID GUCCGUAUUCCCAAGG 245-268 NO: 342 ACCA NO: 618 AGCAG SEQ ID AGAAGGACAGAACUCCCUG SEQ ID AGCAGGGAGUUCUGUC 261-284 NO: 343 CUCC NO: 619 CUUCU SEQ ID AAGGACAGAACUCCCUGCU SEQ ID GGAGCAGGGAGUUCUG 259-282 NO: 344 CCUU NO: 620 UCCUU SEQ ID GAACUCCCUGCUCCUUGGG SEQ ID UUCCCAAGGAGCAGGG 252-275 NO: 345 AAUA NO: 621 AGUUC SEQ ID AGGACAGAACUCCCUGCUC SEQ ID AGGAGCAGGGAGUUCU 258-281 NO: 346 CUUG NO: 622 GUCCU SEQ ID GAAGUUAAGAGCCUGGGUG SEQ ID CCCACCCAGGCUCUUA 317-340 NO: 347 GGGA NO: 623 ACUUC SEQ ID UCUUUGAAGGCGAAGUUAA SEQ ID UCUUAACUUCGCCUUC 328-351 NO: 348 GAGC NO: 624 AAAGA SEQ ID UAUUUAUCAGGAGUGACUG SEQ ID UUCAGUCACUCCUGAU 1174-1197 NO: 349 AAAU NO: 625 AAAUA SEQ ID GUUAUUUAUCAGGAGUGAC SEQ ID CAGUCACUCCUGAUAA 1176-1199 NO: 350 UGAA NO: 626 AUAAC SEQ ID UUAUUUAUCAGGAGUGACU SEQ ID UCAGUCACUCCUGAUA 1175-1198 NO: 351 GAAA NO: 627 AAUAA SEQ ID AAAUACAAUUGAGUCCCAU SEQ ID UGAUGGGACUCAAUUG 1148-1171 NO: 352 CAUC NO: 628 UAUUU SEQ ID AAAAUACAAUUGAGUCCCA SEQ ID GAUGGGACUCAAUUGU 1149-1172 NO: 353 UCAU NO: 629 AUUUU SEQ ID AUUUGUUAUUUAUCAGGAG SEQ ID CACUCCUGAUAAAUAA 1180-1203 NO: 354 UGAC NO: 630 CAAAU SEQ ID GAGAAAACUGGUCAGAUGA SEQ ID AUUCAUCUGACCAGUU 1103-1126 NO: 355 AUAU NO: 631 UUCUC SEQ ID AUAUAAUACAACAUGCCUG SEQ ID AACAGGCAUGUUGUAU 996-1019 NO: 356 UUCA NO: 632 UAUAU SEQ ID UGGGAUCCGGAAGCAUUCC SEQ ID AGGGAAUGCUUCCGGA 666-689 NO: 357 CUUU NO: 633 UCCCA SEQ ID UUGGGAUCCGGAAGCAUUC SEQ ID GGGAAUGCUUCCGGAU 667-690 NO: 358 CCUU NO: 634 CCCAA SEQ ID CAGGCAGUCACCGAGGCCU SEQ ID CGAGGCCUCGGUGACU 533-556 NO: 359 CGGA NO: 635 GCCUG SEQ ID UAUAUAAUACAACAUGCCU SEQ ID ACAGGCAUGUUGUAUU 997-1020 NO: 360 GUUC NO: 636 AUAUA SEQ ID AGUCUAUAAUGCCUUUGUA SEQ ID AAUACAAAGGCAUUAU 219-242 NO: 361 UUGC NO: 637 AGACU SEQ ID UUUAUCAGGAGUGACUGAA SEQ ID AUUUCAGUCACUCCUG 1172-1195 NO: 362 AUAA NO: 638 AUAAA SEQ ID AAUACAAUUGAGUCCCAUC SEQ ID AUGAUGGGACUCAAUU 1147-1170 NO: 363 AUCA NO: 639 GUAUU SEQ ID CUUUAAGAGAAAACUGGUC SEQ ID CUGACCAGUUUUCUCU 1109-1132 NO: 364 AGAU NO: 640 UAAAG SEQ ID GCUUUAAGAGAAAACUGGU SEQ ID UGACCAGUUUUCUCUU 1110-1133 NO: 365 CAGA NO: 641 AAAGC SEQ ID AAUGCCUUUGUAUUGCUUA SEQ ID GAUAAGCAAUACAAAG 212-235 NO: 366 UCUG NO: 642 GCAUU SEQ ID UAAUGCCUUUGUAUUGCUU SEQ ID AUAAGCAAUACAAAGG 213-236 NO: 367 AUCU NO: 643 CAUUA SEQ ID UACCCUGCACAGACACGUU SEQ ID UUAACGUGUCUGUGCA 600-623 NO: 368 AAAG NO: 644 GGGUA SEQ ID AUACCCUGCACAGACACGU SEQ ID UAACGUGUCUGUGCAG 601-624 NO: 369 UAAA NO: 645 GGUAU SEQ ID AUCCAGCUGAUGACGAUGU SEQ ID UCACAUCGUCAUCAGC 694-717 NO: 370 GAGU NO: 646 UGGAU SEQ ID UACAAUUGAGUCCCAUCAU SEQ ID UGAUGAUGGGACUCAA 1145-1168 NO: 371 CAUC NO: 647 UUGUA SEQ ID UGGGAAUACGGACCACGCA SEQ ID ACUGCGUGGUCCGUAU 237-260 NO: 372 GUCU NO: 648 UCCCA SEQ ID UAUAAUACAACAUGCCUGU SEQ ID GAACAGGCAUGUUGUA 995-1018 NO: 373 UCAC NO: 649 UUAUA SEQ ID UUAUCAGGAGUGACUGAAA SEQ ID UAUUUCAGUCACUCCU 1171-1194 NO: 374 UAAA NO: 650 GAUAA SEQ ID AUAAUGCCUUUGUAUUGCU SEQ ID UAAGCAAUACAAAGGC 214-237 NO: 375 UAUC NO: 651 AUUAU SEQ ID CCAGCUGAUGACGAUGUGA SEQ ID ACUCACAUCGUCAUCA 692-715 NO: 376 GUGU NO: 652 GCUGG SEQ ID CAUAGAUACCGAAGUAGGC SEQ ID CCGCCUACUUCGGUAU 636-659 NO: 377 GGCU NO: 653 CUAUG SEQ ID CAUCCAGCUGAUGACGAUG SEQ ID CACAUCGUCAUCAGCU 695-718 NO: 378 UGAG NO: 654 GGAUG SEQ ID GUCAUAGAUACCGAAGUAG SEQ ID GCCUACUUCGGUAUCU 638-661 NO: 379 GCGG NO: 655 AUGAC SEQ ID ACCCUGCACAGACACGUUA SEQ ID UUUAACGUGUCUGUGC 599-622 NO: 380 AAGC NO: 656 AGGGU SEQ ID UGCAUCAUCAUGCGGCGGC SEQ ID UCGCCGCCGCAUGAUG 772-795 NO: 381 GAAC NO: 657 AUGCA SEQ ID CGGACCACGCAGUCUAUAA SEQ ID CAUUAUAGACUGCGUG 229-252 NO: 382 UGCC NO: 658 GUCCG SEQ ID CUUGGGAAUACGGACCACG SEQ ID UGCGUGGUCCGUAUUC 239-262 NO: 383 CAGU NO: 659 CCAAG SEQ ID GAAGUAGGCGGCUCGGUAG SEQ ID AUCUACCGAGCCGCCU 626-649 NO: 384 AUGA NO: 660 ACUUC SEQ ID CUGCUAGACGGGUACGGGC SEQ ID UUGCCCGUACCCGUCU 477-500 NO: 385 AAAA NO: 661 AGCAG SEQ ID UCCAGCUGAUGACGAUGUG SEQ ID CUCACAUCGUCAUCAG 693-716 NO: 386 AGUG NO: 662 CUGGA SEQ ID AUACGGACCACGCAGUCUA SEQ ID UAUAGACUGCGUGGUC 232-255 NO: 387 UAAU NO: 663 CGUAU SEQ ID AACCAGGCAGUCACCGAGG SEQ ID GGCCUCGGUGACUGCC 536-559 NO: 388 CCUC NO: 664 UGGUU SEQ ID UGACAGUCUGUGCGAUCAU SEQ ID GGAUGAUCGCACAGAC 711-734 NO: 389 CCAG NO: 665 UGUCA SEQ ID UAGACGGGUACGGGCAAAA SEQ ID GAUUUUGCCCGUACCC 473-496 NO: 390 UCAA NO: 666 GUCUA SEQ ID GCAGUGACAGUCUGUGCGA SEQ ID GAUCGCACAGACUGUC 715-738 NO: 391 UCAU NO: 667 ACUGC SEQ ID AGUGACAGUCUGUGCGAUC SEQ ID AUGAUCGCACAGACUG 713-736 NO: 392 AUCC NO: 668 UCACU SEQ ID GCUAGACGGGUACGGGCAA SEQ ID UUUUGCCCGUACCCGU 475-498 NO: 393 AAUC NO: 669 CUAGC SEQ ID AGUAGGCGGCUCGGUAGAU SEQ ID UCAUCUACCGAGCCGC 624-647 NO: 394 GAUA NO: 670 CUACU SEQ ID GAAUACGGACCACGCAGUC SEQ ID UAGACUGCGUGGUCCG 234-257 NO: 395 UAUA NO: 671 UAUUC SEQ ID CUUUGUAUUGCUUAUCUGC SEQ ID CUGCAGAUAAGCAAUA 207-230 NO: 396 AGUG NO: 672 CAAAG SEQ ID UUUGUAUUGCUUAUCUGCA SEQ ID ACUGCAGAUAAGCAAU 206-229 NO: 397 GUGA NO: 673 ACAAA SEQ ID UUGUAUUGCUUAUCUGCAG SEQ ID CACUGCAGAUAAGCAA 205-228 NO: 398 UGAU NO: 674 UACAA SEQ ID UAUCUGCAGUGAUCUGCUU SEQ ID GCAAGCAGAUCACUGC 195-218 NO: 399 GCUG NO: 675 AGAUA SEQ ID GUAUUGCUUAUCUGCAGUG SEQ ID AUCACUGCAGAUAAGC 203-226 NO: 400 AUCU NO: 676 AAUAC SEQ ID UGUAUUGCUUAUCUGCAGU SEQ ID UCACUGCAGAUAAGCA 204-227 NO: 401 GAUC NO: 677 AUACA SEQ ID UGCUUAUCUGCAGUGAUCU SEQ ID GCAGAUCACUGCAGAU 199-222 NO: 402 GCUU NO: 678 AAGCA SEQ ID UUGCUUAUCUGCAGUGAUC SEQ ID CAGAUCACUGCAGAUA 200-223 NO: 403 UGCU NO: 679 AGCAA SEQ ID AUCUGCAGUGAUCUGCUUG SEQ ID AGCAAGCAGAUCACUG 194-217 NO: 404 CUGG NO: 680 CAGAU SEQ ID UAUUGCUUAUCUGCAGUGA SEQ ID GAUCACUGCAGAUAAG 202-225 NO: 405 UCUG NO: 681 CAAUA SEQ ID UUCUCCAAAUUUGUUAUUU SEQ ID AUAAAUAACAAAUUUG 1188-1211 NO: 406 AUCA NO: 682 GAGAA SEQ ID CAAAUUUGUUAUUUAUCAG SEQ ID UCCUGAUAAAUAACAA 1183-1206 NO: 407 GAGU NO: 683 AUUUG SEQ ID GAGGCCUCGGAAUUCCCUU SEQ ID GAAAGGGAAUUCCGAG 521-544 NO: 408 UCAG NO: 684 GCCUC SEQ ID AGAUAUGUUAUAUAAUACA SEQ ID GUUGUAUUAUAUAACA 1005-1028 NO: 409 ACAU NO: 685 UAUCU SEQ ID GCAGUCACCGAGGCCUCGG SEQ ID UUCCGAGGCCUCGGUG 530-553 NO: 410 AAUU NO: 686 ACUGC SEQ ID CGAGGCCUCGGAAUUCCCU SEQ ID AAAGGGAAUUCCGAGG 522-545 NO: 411 UUCA NO: 687 CCUCG SEQ ID CAAGAUAUGUUAUAUAAUA SEQ ID UGUAUUAUAUAACAUA 1007-1030 NO: 412 CAAC NO: 688 UCUUG SEQ ID AGUCACCGAGGCCUCGGAA SEQ ID AAUUCCGAGGCCUCGG 528-551 NO: 413 UUCC NO: 689 UGACU SEQ ID CACCGAGGCCUCGGAAUUC SEQ ID GGGAAUUCCGAGGCCU 525-548 NO: 414 CCUU NO: 690 CGGUG SEQ ID CCUCGGAAUUCCCUUUCAG SEQ ID AGCUGAAAGGGAAUUC 517-540 NO: 415 CUCC NO: 691 CGAGG SEQ ID UCGGAAUUCCCUUUCAGCU SEQ ID GGAGCUGAAAGGGAAU 515-538 NO: 416 CCAG NO: 692 UCCGA SEQ ID GGCCUCGGAAUUCCCUUUC SEQ ID CUGAAAGGGAAUUCCG 519-542 NO: 417 AGCU NO: 693 AGGCC SEQ ID CUCGGAAUUCCCUUUCAGC SEQ ID GAGCUGAAAGGGAAUU 516-539 NO: 418 UCCA NO: 694 CCGAG SEQ ID GCCUCGGAAUUCCCUUUCA SEQ ID GCUGAAAGGGAAUUCC 518-541 NO: 419 GCUC NO: 695 GAGGC SEQ ID AUGUUAUAUAAUACAACAU SEQ ID GCAUGUUGUAUUAUAU 1001-1024 NO: 420 GCCU NO: 696 AACAU SEQ ID AAGAUAUGUUAUAUAAUAC SEQ ID UUGUAUUAUAUAACAU 1006-1029 NO: 421 AACA NO: 697 AUCUU SEQ ID UCAAGAUAUGUUAUAUAAU SEQ ID GUAUUAUAUAACAUAU 1008-1031 NO: 422 ACAA NO: 698 CUUGA SEQ ID UGUUAUAUAAUACAACAUG SEQ ID GGCAUGUUGUAUUAUA 1000-1023 NO: 423 CCUG NO: 699 UAACA SEQ ID CCGAGGCCUCGGAAUUCCC SEQ ID AAGGGAAUUCCGAGGC 523-546 NO: 424 UUUC NO: 700 CUCGG SEQ ID GUCACCGAGGCCUCGGAAU SEQ ID GAAUUCCGAGGCCUCG 527-550 NO: 425 UCCC NO: 701 GUGAC SEQ ID ACCGAGGCCUCGGAAUUCC SEQ ID AGGGAAUUCCGAGGCC 524-547 NO: 426 CUUU NO: 702 UCGGU SEQ ID UCACCGAGGCCUCGGAAUU SEQ ID GGAAUUCCGAGGCCUC 526-549 NO: 427 CCCU NO: 703 GGUGA SEQ ID AUUUCAUCAUACAAGACAA SEQ ID GCUUGUCUUGUAUGAU 931-954 NO: 428 GCAC NO: 704 GAAAU SEQ ID UGUAUUUAUCUUUGAAGGC SEQ ID UCGCCUUCAAAGAUAA 336-359 NO: 429 GAAG NO: 705 AUACA SEQ ID AUUUGUAGAUCUUAACCAG SEQ ID GCCUGGUUAAGAUCUA 549-572 NO: 430 GCAG NO: 706 CAAAU SEQ ID UUCCCUUUGCAGUGUCAUA SEQ ID UCUAUGACACUGCAAA 651-674 NO: 431 GAUA NO: 707 GGGAA SEQ ID AUCAUACAAGACAAGCACA SEQ ID UUUGUGCUUGUCUUGU 926-949 NO: 432 AAAG NO: 708 AUGAU SEQ ID UAGAUCUUAACCAGGCAGU SEQ ID UGACUGCCUGGUUAAG 544-567 NO: 433 CACC NO: 709 AUCUA SEQ ID AAGCAUUCCCUUUGCAGUG SEQ ID GACACUGCAAAGGGAA 656-679 NO: 434 UCAU NO: 710 UGCUU SEQ ID UUUGCAGUGUCAUAGAUAC SEQ ID CGGUAUCUAUGACACU 646-669 NO: 435 CGAA NO: 711 GCAAA SEQ ID AGAGAAAACUGGUCAGAUG SEQ ID UUCAUCUGACCAGUUU 1104-1127 NO: 436 AAUA NO: 712 UCUCU SEQ ID UGCAGUGUCAUAGAUACCG SEQ ID UUCGGUAUCUAUGACA 644-667 NO: 437 AAGU NO: 713 CUGCA SEQ ID UCAGAUUUGUAGAUCUUAA SEQ ID GGUUAAGAUCUACAAA 553-576 NO: 438 CCAG NO: 714 UCUGA SEQ ID GAACAUUGGACCAUGCACC SEQ ID AGGGUGCAUGGUCCAA 885-908 NO: 440 CUUG NO: 716 UGUUC SEQ ID AAUCCCAUCAGAUUUGUAG SEQ ID AUCUACAAAUCUGAUG 560-583 NO: 441 AUCU NO: 717 GGAUU SEQ ID GCAGUGUCAUAGAUACCGA SEQ ID CUUCGGUAUCUAUGAC 643-666 NO: 442 AGUA NO: 718 ACUGC SEQ ID CAAGCACAAAAGCACCACC SEQ ID UGGGUGGUGCUUUUGU 915-938 NO: 443 CAUG NO: 719 GCUUG SEQ ID GCGGCUCGGUAGAUGAUAA SEQ ID UAUUAUCAUCUACCGA 619-642 NO: 444 UACC NO: 720 GCCGC SEQ ID CUCCUUGGGAAUACGGACC SEQ ID GUGGUCCGUAUUCCCA 242-265 NO: 445 ACGC NO: 721 AGGAG SEQ ID AUUCCCUUUGCAGUGUCAU SEQ ID CUAUGACACUGCAAAG 652-675 NO: 446 AGAU NO: 722 GGAAU SEQ ID CAUACAAGACAAGCACAAA SEQ ID CUUUUGUGCUUGUCUU 924-947 NO: 447 AGCA NO: 723 GUAUG SEQ ID AGACACGUUAAAGCCUUGG SEQ ID UACCAAGGCUUUAACG 590-613 NO: 448 UACA NO: 724 UGUCU SEQ ID UGAGAACAUUGGACCAUGC SEQ ID GUGCAUGGUCCAAUGU 888-911 NO: 449 ACCC NO: 725 UCUCA SEQ ID GCUUGUAUUUAUCUUUGAA SEQ ID CCUUCAAAGAUAAAUA 339-362 NO: 450 GGCG NO: 726 CAAGC SEQ ID GCUCGGUAGAUGAUAAUAC SEQ ID GGGUAUUAUCAUCUAC 616-639 NO: 451 CCUG NO: 727 CGAGC SEQ ID AGUGUCAUAGAUACCGAAG SEQ ID UACUUCGGUAUCUAUG 641-664 NO: 452 UAGG NO: 728 ACACU SEQ ID GGUAGAUGAUAAUACCCUG SEQ ID UGCAGGGUAUUAUCAU 612-635 NO: 454 CACA NO: 730 CUACC SEQ ID CAGGCCCUUAAUCCCAUCA SEQ ID UCUGAUGGGAUUAAGG 569-592 NO: 455 GAUU NO: 731 GCCUG SEQ ID AGAUGAUAAUACCCUGCAC SEQ ID CUGUGCAGGGUAUUAU 609-632 NO: 456 AGAC NO: 732 CAUCU SEQ ID UACAGGCCCUUAAUCCCAU SEQ ID UGAUGGGAUUAAGGGC 571-594 NO: 457 CAGA NO: 733 CUGUA SEQ ID ACAGACACGUUAAAGCCUU SEQ ID CCAAGGCUUUAACGUG 592-615 NO: 458 GGUA NO: 734 UCUGU SEQ ID AGAAAACUGGUCAGAUGAA SEQ ID UAUUCAUCUGACCAGU 1102-1125 NO: 459 UAUU NO: 735 UUUCU SEQ ID UGUAGAUCUUAACCAGGCA SEQ ID ACUGCCUGGUUAAGAU 546-569 NO: 460 GUCA NO: 736 CUACA SEQ ID UCAAAUGGAUAGGAAGUCA SEQ ID GUUGACUUCCUAUCCA 745-768 NO: 461 ACCC NO: 737 UUUGA SEQ ID CAUUCCCUUUGCAGUGUCA SEQ ID UAUGACACUGCAAAGG 653-676 NO: 462 UAGA NO: 738 GAAUG SEQ ID CAUCAGAUUUGUAGAUCUU SEQ ID UUAAGAUCUACAAAUC 555-578 NO: 463 AACC NO: 739 UGAUG SEQ ID CUCGGUAGAUGAUAAUACC SEQ ID AGGGUAUUAUCAUCUA 615-638 NO: 464 CUGC NO: 740 CCGAG SEQ ID UUUGUAGAUCUUAACCAGG SEQ ID UGCCUGGUUAAGAUCU 548-571 NO: 465 CAGU NO: 741 ACAAA SEQ ID ACAGGCCCUUAAUCCCAUC SEQ ID CUGAUGGGAUUAAGGG 570-593 NO: 466 AGAU NO: 742 CCUGU SEQ ID CUUUGCAGUGUCAUAGAUA SEQ ID GGUAUCUAUGACACUG 647-670 NO: 467 CCGA NO: 743 CAAAG SEQ ID CACAUCAGCUGCUAGACGG SEQ ID ACCCGUCUAGCAGCUG 485-508 NO: 468 GUAC NO: 744 AUGUG SEQ ID CCCUUUGCAGUGUCAUAGA SEQ ID UAUCUAUGACACUGCA 649-672 NO: 469 UACC NO: 745 AAGGG SEQ ID CUCCAGCUUUACCCACAUC SEQ ID CUGAUGUGGGUAAAGC 498-521 NO: 470 AGCU NO: 746 UGGAG SEQ ID UUACCCACAUCAGCUGCUA SEQ ID UCUAGCAGCUGAUGUG 490-513 NO: 471 GACG NO: 747 GGUAA SEQ ID UUAAAGCCUUGGUACAGGC SEQ ID GGGCCUGUACCAAGGC 583-606 NO: 472 CCUU NO: 748 UUUAA SEQ ID CAGCUGCUAGACGGGUACG SEQ ID CCCGUACCCGUCUAGC 480-503 NO: 473 GGCA NO: 749 AGCUG SEQ ID CAGCUUUACCCACAUCAGC SEQ ID CAGCUGAUGUGGGUAA 495-518 NO: 474 UGCU NO: 750 AGCUG SEQ ID UCAGCUGCUAGACGGGUAC SEQ ID CCGUACCCGUCUAGCA 481-504 NO: 475 GGGC NO: 751 GCUGA SEQ ID UCCAGCUUUACCCACAUCA SEQ ID GCUGAUGUGGGUAAAG 497-520 NO: 476 GCUG NO: 752 CUGGA SEQ ID GGCUCGGUAGAUGAUAAUA SEQ ID GGUAUUAUCAUCUACC 617-640 NO: 477 CCCU NO: 753 GAGCC SEQ ID AGGCGGCUCGGUAGAUGAU SEQ ID UUAUCAUCUACCGAGC 621-644 NO: 478 AAUA NO: 754 CGCCU SEQ ID CAUCAGCUGCUAGACGGGU SEQ ID GUACCCGUCUAGCAGC 483-506 NO: 479 ACGG NO: 755 UGAUG SEQ ID GUACAGGCCCUUAAUCCCA SEQ ID GAUGGGAUUAAGGGCC 572-595 NO: 480 UCAG NO: 756 UGUAC SEQ ID AUGAUAAUACCCUGCACAG SEQ ID GUCUGUGCAGGGUAUU 607-630 NO: 481 ACAC NO: 757 AUCAU SEQ ID CCUUGGGAAUACGGACCAC SEQ ID GCGUGGUCCGUAUUCC 240-263 NO: 482 GCAG NO: 758 CAAGG SEQ ID UCCUUGGGAAUACGGACCA SEQ ID CGUGGUCCGUAUUCCC 241-264 NO: 483 CGCA NO: 759 AAGGA SEQ ID CAGAUUUGUAGAUCUUAAC SEQ ID UGGUUAAGAUCUACAA 552-575 NO: 484 CAGG NO: 760 AUCUG SEQ ID UGUACUUCUUGAUUUCAUC SEQ ID AUGAUGAAAUCAAGAA 942-965 NO: 485 AUAC NO: 761 GUACA SEQ ID AUCCCAUCAGAUUUGUAGA SEQ ID GAUCUACAAAUCUGAU 559-582 NO: 486 UCUU NO: 762 GGGAU SEQ ID GUAGAUGAUAAUACCCUGC SEQ ID GUGCAGGGUAUUAUCA 611-634 NO: 487 ACAG NO: 763 UCUAC SEQ ID GACACGUUAAAGCCUUGGU SEQ ID GUACCAAGGCUUUAAC 589-612 NO: 488 ACAG NO: 764 GUGUC SEQ ID AGCUUUACCCACAUCAGCU SEQ ID GCAGCUGAUGUGGGUA 494-517 NO: 489 GCUA NO: 765 AAGCU SEQ ID AAGCACAAAAGCACCACCC SEQ ID AUGGGUGGUGCUUUUG 914-937 NO: 490 AUGC NO: 766 UGCUU SEQ ID AUCUUAACCAGGCAGUCAC SEQ ID CGGUGACUGCCUGGUU 541-564 NO: 491 CGAG NO: 767 AAGAU SEQ ID UUUACCCACAUCAGCUGCU SEQ ID CUAGCAGCUGAUGUGG 491-514 NO: 492 AGAC NO: 768 GUAAA SEQ ID CUUAAUCCCAUCAGAUUUG SEQ ID UACAAAUCUGAUGGGA 563-586 NO: 493 UAGA NO: 769 UUAAG SEQ ID CAGUGUCAUAGAUACCGAA SEQ ID ACUUCGGUAUCUAUGA 642-665 NO: 494 GUAG NO: 770 CACUG SEQ ID CCAGCUUUACCCACAUCAG SEQ ID AGCUGAUGUGGGUAAA 496-519 NO: 495 CUGC NO: 771 GCUGG SEQ ID GAUGAUAAUACCCUGCACA SEQ ID UCUGUGCAGGGUAUUA 608-631 NO: 497 GACA NO: 773 UCAUC SEQ ID UUUCAUCAUACAAGACAAG SEQ ID UGCUUGUCUUGUAUGA 930-953 NO: 498 CACA NO: 774 UGAAA SEQ ID CAGACACGUUAAAGCCUUG SEQ ID ACCAAGGCUUUAACGU 591-614 NO: 499 GUAC NO: 775 GUCUG SEQ ID AGAACAUUGGACCAUGCAC SEQ ID GGGUGCAUGGUCCAAU 886-909 NO: 500 CCUU NO: 776 GUUCU SEQ ID GUAGAUCUUAACCAGGCAG SEQ ID GACUGCCUGGUUAAGA 545-568 NO: 501 UCAC NO: 777 UCUAC SEQ ID AGCUCCAGCUUUACCCACA SEQ ID GAUGUGGGUAAAGCUG 500-523 NO: 502 UCAG NO: 778 GAGCU SEQ ID GCUCCUUGGGAAUACGGAC SEQ ID UGGUCCGUAUUCCCAA 243-266 NO: 503 CACG NO: 779 GGAGC SEQ ID GAAGCAUUCCCUUUGCAGU SEQ ID ACACUGCAAAGGGAAU 657-680 NO: 504 GUCA NO: 780 GCUUC SEQ ID CCUUGGUACAGGCCCUUAA SEQ ID GAUUAAGGGCCUGUAC 577-600 NO: 505 UCCC NO: 781 CAAGG SEQ ID UAGAUGAUAAUACCCUGCA SEQ ID UGUGCAGGGUAUUAUC 610-633 NO: 506 CAGA NO: 782 AUCUA SEQ ID AAUACCCUGCACAGACACG SEQ ID AACGUGUCUGUGCAGG 602-625 NO: 507 UUAA NO: 783 GUAUU SEQ ID GUUAAAGCCUUGGUACAGG SEQ ID GGCCUGUACCAAGGCU 584-607 NO: 508 CCCU NO: 784 UUAAC SEQ ID AGCAUUCCCUUUGCAGUGU SEQ ID UGACACUGCAAAGGGA 655-678 NO: 509 CAUA NO: 785 AUGCU SEQ ID UCUUAACCAGGCAGUCACC SEQ ID UCGGUGACUGCCUGGU 540-563 NO: 510 GAGG NO: 786 UAAGA SEQ ID AUACAAGACAAGCACAAAA SEQ ID GCUUUUGUGCUUGUCU 923-946 NO: 511 GCAC NO: 787 UGUAU SEQ ID GACAAGCACAAAAGCACCA SEQ ID GGUGGUGCUUUUGUGC 917-940 NO: 512 CCCA NO: 788 UUGUC SEQ ID ACCCACAUCAGCUGCUAGA SEQ ID CGUCUAGCAGCUGAUG 488-511 NO: 513 CGGG NO: 789 UGGGU SEQ ID UAAAGCCUUGGUACAGGCC SEQ ID AGGGCCUGUACCAAGG 582-605 NO: 514 CUUA NO: 790 CUUUA SEQ ID UUCAUCAUACAAGACAAGC SEQ ID GUGCUUGUCUUGUAUG 929-952 NO: 515 ACAA NO: 791 AUGAA SEQ ID GCCCUUAAUCCCAUCAGAU SEQ ID AAAUCUGAUGGGAUUA 566-589 NO: 516 UUGU NO: 792 AGGGC SEQ ID UUAAUCCCAUCAGAUUUGU SEQ ID CUACAAAUCUGAUGGG 562-585 NO: 517 AGAU NO: 793 AUUAA SEQ ID UCGGUAGAUGAUAAUACCC SEQ ID CAGGGUAUUAUCAUCU 614-637 NO: 518 UGCA NO: 794 ACCGA SEQ ID CACGUUAAAGCCUUGGUAC SEQ ID CUGUACCAAGGCUUUA 587-610 NO: 519 AGGC NO: 795 ACGUG SEQ ID UCCCAUCAGAUUUGUAGAU SEQ ID AGAUCUACAAAUCUGA 558-581 NO: 520 CUUA NO: 796 UGGGA SEQ ID UCAUACAAGACAAGCACAA SEQ ID UUUUGUGCUUGUCUUG 925-948 NO: 521 AAGC NO: 797 UAUGA SEQ ID CCUUAAUCCCAUCAGAUUU SEQ ID ACAAAUCUGAUGGGAU 564-587 NO: 522 GUAG NO: 798 UAAGG SEQ ID ACAUUGGACCAUGCACCCU SEQ ID CAAGGGUGCAUGGUCC 883-906 NO: 523 UGAA NO: 799 AAUGU SEQ ID CUUGGUACAGGCCCUUAAU SEQ ID GGAUUAAGGGCCUGUA 576-599 NO: 524 CCCA NO: 800 CCAAG SEQ ID UUGCAGUGUCAUAGAUACC SEQ ID UCGGUAUCUAUGACAC 645-668 NO: 525 GAAG NO: 801 UGCAA SEQ ID CACAGACACGUUAAAGCCU SEQ ID CAAGGCUUUAACGUGU 593-616 NO: 526 UGGU NO: 802 CUGUG SEQ ID AGCACAAAAGCACCACCCA SEQ ID CAUGGGUGGUGCUUUU 913-936 NO: 527 UGCC NO: 803 GUGCU SEQ ID CCAUCAGAUUUGUAGAUCU SEQ ID UAAGAUCUACAAAUCU 556-579 NO: 528 UAAC NO: 804 GAUGG SEQ ID CCACAUCAGCUGCUAGACG SEQ ID CCCGUCUAGCAGCUGA 486-509 NO: 529 GGUA NO: 805 UGUGG SEQ ID GCAUUCCCUUUGCAGUGUC SEQ ID AUGACACUGCAAAGGG 654-677 NO: 530 AUAG NO: 806 AAUGC SEQ ID CUUUACCCACAUCAGCUGC SEQ ID UAGCAGCUGAUGUGGG 492-515 NO: 531 UAGA NO: 807 UAAAG SEQ ID AUCCGGAAGCAUUCCCUUU SEQ ID GCAAAGGGAAUGCUUC 662-685 NO: 532 GCAG NO: 808 CGGAU SEQ ID AGCUGCUAGACGGGUACGG SEQ ID GCCCGUACCCGUCUAG 479-502 NO: 533 GCAA NO: 809 CAGCU SEQ ID CGGCUCGGUAGAUGAUAAU SEQ ID GUAUUAUCAUCUACCG 618-641 NO: 534 ACCC NO: 810 AGCCG SEQ ID GGGUACGGGCAAAAUCAAG SEQ ID CUCUUGAUUUUGCCCG 468-491 NO: 535 AGGG NO: 811 UACCC SEQ ID ACAUCAGCUGCUAGACGGG SEQ ID UACCCGUCUAGCAGCU 484-507 NO: 536 UACG NO: 812 GAUGU SEQ ID CCCUUAAUCCCAUCAGAUU SEQ ID CAAAUCUGAUGGGAUU 565-588 NO: 537 UGUA NO: 813 AAGGG SEQ ID CGGGCAAAAUCAAGAGGGU SEQ ID GUACCCUCUUGAUUUU 463-486 NO: 538 ACAC NO: 814 GCCCG SEQ ID ACGUUAAAGCCUUGGUACA SEQ ID CCUGUACCAAGGCUUU 586-609 NO: 539 GGCC NO: 815 AACGU SEQ ID UGGUACAGGCCCUUAAUCC SEQ ID UGGGAUUAAGGGCCUG 574-597 NO: 540 CAUC NO: 816 UACCA SEQ ID GGCGGCUCGGUAGAUGAUA SEQ ID AUUAUCAUCUACCGAG 620-643 NO: 541 AUAC NO: 817 CCGCC SEQ ID CGUUAAAGCCUUGGUACAG SEQ ID GCCUGUACCAAGGCUU 585-608 NO: 542 GCCC NO: 818 UAACG SEQ ID GGUACAGGCCCUUAAUCCC SEQ ID AUGGGAUUAAGGGCCU 573-596 NO: 543 AUCA NO: 819 GUACC SEQ ID UAAUACCCUGCACAGACAC SEQ ID ACGUGUCUGUGCAGGG 603-626 NO: 544 GUUA NO: 820 UAUUA SEQ ID GACCACGCAGUCUAUAAUG SEQ ID GGCAUUAUAGACUGCG 227-250 NO: 545 CCUU NO: 821 UGGUC SEQ ID GUUAAGAGCCUGGGUGGGG SEQ ID UUCCCCACCCAGGCUC 314-337 NO: 546 AAGU NO: 822 UUAAC SEQ ID UGGGGAAGUAUCUGAUGAC SEQ ID AUGUCAUCAGAUACUU 300-323 NO: 547 AUUG NO: 823 CCCCA SEQ ID GGUGGGGAAGUAUCUGAUG SEQ ID GUCAUCAGAUACUUCC 302-325 NO: 548 ACAU NO: 824 CCACC SEQ ID GUGGGGAAGUAUCUGAUGA SEQ ID UGUCAUCAGAUACUUC 301-324 NO: 549 CAUU NO: 825 CCCAC SEQ ID GGGGAAGUAUCUGAUGACA SEQ ID AAUGUCAUCAGAUACU 299-322 NO: 550 UUGG NO: 826 UCCCC SEQ ID UUAAGAGCCUGGGUGGGGA SEQ ID CUUCCCCACCCAGGCU 313-336 NO: 551 AGUA NO: 827 CUUAA SEQ ID CCGAAGUAGGCGGCUCGGU SEQ ID CUACCGAGCCGCCUAC 628-651 NO: 552 AGAU NO: 828 UUCGG In a particular embodiment, the invention relates to a nucleic acid comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO:304 SEQ ID NO:580 SEQ ID NO:323 SEQ ID NO:599 SEQ ID NO:439 SEQ ID NO:715 SEQ ID NO:453 SEQ ID NO:729 SEQ ID NO:496 SEQ ID NO:772 In a particularly preferred embodiment, the invention relates to a nucleic acid comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO:304 SEQ ID NO:580 In certain embodiments, the nucleic acid for inhibiting expression of the SLC25A5 gene comprises a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO:829-1104. In certain embodiments, the first strand comprises nucleosides 2-18 of any one of the sequences set forth in SEQ ID NO: 829-1104. In certain embodiments, the nucleic acid for inhibiting expression of the SLC25A5 gene comprises a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 21 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 829-1104. In certain embodiments, the first strand comprises nucleosides 2-22 of any one of the sequences set forth in SEQ ID NO: 829-1104. In certain embodiments, the first strand comprises any one of SEQ ID NO: 829-1104. The modification pattern of the nucleic acids as set forth in SEQ ID NO: 829-1104 is summarized in Table 3 below: Table 3 provides the modified first (antisense) sequences, together with the corresponding unmodified first (antisense) sequences for siRNA oligonucleosides according to the present invention as follows. Table 3 Antisense Modified Antisense Strand SEQ ID Underlying Base SEQ ID strand ID 5’ ^ 3’ NO (AS - Sequence NO (AS - mod) 5’ ^ 3’ unmod) (Shown as an Unmodified Nucleotide Sequence) ETX- UmsUfsAmAmGmAfGmAmAmAmAmCm SEQ ID UUAAGAGAAAAC SEQ ID S00003198 UmGfGmUfCmAfGmAmUmsGmsAm NO: 856 UGGUCAGAUGA NO: 304 ETX- UmsAfsUmCmAmGfGmAmGmUmGmAm SEQ ID UAUCAGGAGUGA SEQ ID S00003274 CmUfGmAfAmAfUmAmAmsAmsAm NO: 875 CUGAAAUAAAA NO: 323 ETX- UmsCfsCmCmUmUfUmGmCmAmGmUm SEQ ID UCCCUUUGCAGU SEQ ID S00003738 GmUfCmAfUmAfGmAmUmsAmsCm NO: 991 GUCAUAGAUAC NO: 439 ETX- AmsUfsCmAmGmAfUmUmUmGmUmAm SEQ ID AUCAGAUUUGUA SEQ ID S00003794 GmAfUmCfUmUfAmAmCmsCmsAm NO: 1005 GAUCUUAACCA NO: 453 ETX- AmsUfsCmAmGmCfUmGmCmUmAmGm SEQ ID AUCAGCUGCUAG SEQ ID S00003966 AmCfGmGfGmUfAmCmGmsGmsGm NO: 1048 ACGGGUACGGG NO: 496 ETX- CmsCfsCmAmUmUfUmUmCmAmAmCm SEQ ID CCCAUUUUCAAC SEQ ID S00003090 CmAfGmUfAmAfAmUmAmsGmsUm NO: 829 CAGUAAAUAGU NO: 277 ETX- AmsCfsGmCmAmGfUmCmUmAmUmAm SEQ ID ACGCAGUCUAUA SEQ ID S00003094 AmUfGmCfCmUfUmUmGmsUmsAm NO: 830 AUGCCUUUGUA NO: 278 ETX- GmsUfsGmUmAmCfUmUmCmUmUmGm SEQ ID GUGUACUUCUUG SEQ ID S00003098 AmUfUmUfCmAfUmCmAmsUmsAm NO: 831 AUUUCAUCAUA NO: 279 ETX- AmsUfsAmCmAmAfUmUmGmAmGmUm SEQ ID AUACAAUUGAGU SEQ ID S00003102 CmCfCmAfUmCfAmUmCmsAmsUm NO: 832 CCCAUCAUCAU NO: 280 ETX- GmsGfsAmCmCmAfCmGmCmAmGmUm SEQ ID GGACCACGCAGU SEQ ID S00003106 CmUfAmUfAmAfUmGmCmsCmsUm NO: 833 CUAUAAUGCCU NO: 281 ETX- UmsUfsGmUmUmAfUmUmUmAmUmCm SEQ ID UUGUUAUUUAUC SEQ ID S00003110 AmGfGmAfGmUfGmAmCmsUmsGm NO: 834 AGGAGUGACUG NO: 282 ETX- CmsAfsGmUmCmUfAmUmAmAmUmGm SEQ ID CAGUCUAUAAUG SEQ ID S00003114 CmCfUmUfUmGfUmAmUmsUmsGm NO: 835 CCUUUGUAUUG NO: 283 ETX- AmsUfsAmGmAmUfAmCmCmGmAmAm SEQ ID AUAGAUACCGAA SEQ ID S00003118 GmUfAmGfGmCfGmGmCmsUmsCm NO: 836 GUAGGCGGCUC NO: 284 ETX- UmsAfsGmAmUmAfCmCmGmAmAmGm SEQ ID UAGAUACCGAAG SEQ ID S00003122 UmAfGmGfCmGfGmCmUmsCmsGm NO: 837 UAGGCGGCUCG NO: 285 ETX- GmsGfsAmAmUmAfCmGmGmAmCmCm SEQ ID GGAAUACGGACC SEQ ID S00003126 AmCfGmCfAmGfUmCmUmsAmsUm NO: 838 ACGCAGUCUAU NO: 286 ETX- CmsAfsGmCmUmGfAmUmGmAmCmGm SEQ ID CAGCUGAUGACG SEQ ID S00003130 AmUfGmUfGmAfGmUmGmsUmsUm NO: 839 AUGUGAGUGUU NO: 287 ETX- AmsUfsUmUmAmUfCmUmUmUmGmAm SEQ ID AUUUAUCUUUGA SEQ ID S00003134 AmGfGmCfGmAfAmGmUmsUmsAm NO: 840 AGGCGAAGUUA NO: 288 ETX- GmsUfsGmUmCmAfUmAmGmAmUmAm SEQ ID GUGUCAUAGAUA SEQ ID S00003138 CmCfGmAfAmGfUmAmGmsGmsCm NO: 841 CCGAAGUAGGC NO: 289 ETX- UmsUfsCmCmCmAfUmUmUmUmCmAm SEQ ID UUCCCAUUUUCA SEQ ID S00003142 AmCfCmAfGmUfAmAmAmsUmsAm NO: 842 ACCAGUAAAUA NO: 290 ETX- GmsCfsUmGmCmUfAmGmAmCmGmGm SEQ ID GCUGCUAGACGG SEQ ID S00003146 GmUfAmCfGmGfGmCmAmsAmsAm NO: 843 GUACGGGCAAA NO: 291 ETX- CmsAfsGmUmUmCfCmUmUmUmGmCm SEQ ID CAGUUCCUUUGC SEQ ID S00003150 GmCfCmCfUmGfAmCmUmsGmsCm NO: 844 GCCCUGACUGC NO: 292 ETX- CmsUfsUmCmCmCfAmUmUmUmUmCm SEQ ID CUUCCCAUUUUC SEQ ID S00003154 AmAfCmCfAmGfUmAmAmsAmsUm NO: 845 AACCAGUAAAU NO: 293 ETX- AmsGfsAmUmAmCfCmGmAmAmGmUm SEQ ID AGAUACCGAAGU SEQ ID S00003158 AmGfGmCfGmGfCmUmCmsGmsGm NO: 846 AGGCGGCUCGG NO: 294 ETX- UmsUfsAmAmCmCfAmGmGmCmAmGm SEQ ID UUAACCAGGCAG SEQ ID S00003162 UmCfAmCfCmGfAmGmGmsCmsCm NO: 847 UCACCGAGGCC NO: 295 ETX- AmsUfsCmAmUmCfCmAmGmCmUmGm SEQ ID AUCAUCCAGCUG SEQ ID S00003166 AmUfGmAfCmGfAmUmGmsUmsGm NO: 848 AUGACGAUGUG NO: 296 ETX- AmsUfsUmUmAmUfCmAmGmGmAmGm SEQ ID AUUUAUCAGGAG SEQ ID S00003170 UmGfAmCfUmGfAmAmAmsUmsAm NO: 849 UGACUGAAAUA NO: 297 ETX- GmsAfsCmAmGmUfCmUmGmUmGmCm SEQ ID GACAGUCUGUGC SEQ ID S00003174 GmAfUmCfAmUfCmCmAmsGmsCm NO: 850 GAUCAUCCAGC NO: 298 ETX- UmsCfsUmAmUmAfAmUmGmCmCmUm SEQ ID UCUAUAAUGCCU SEQ ID S00003178 UmUfGmUfAmUfUmGmCmsUmsUm NO: 851 UUGUAUUGCUU NO: 299 ETX- UmsAfsAmCmCmAfGmGmCmAmGmUm SEQ ID UAACCAGGCAGU SEQ ID S00003182 CmAfCmCfGmAfGmGmCmsCmsUm NO: 852 CACCGAGGCCU NO: 300 ETX- CmsCfsCmUmGmCfAmCmAmGmAmCm SEQ ID CCCUGCACAGAC SEQ ID S00003186 AmCfGmUfUmAfAmAmGmsCmsCm NO: 853 ACGUUAAAGCC NO: 301 ETX- CmsAfsCmGmCmAfGmUmCmUmAmUm SEQ ID CACGCAGUCUAU SEQ ID S00003190 AmAfUmGfCmCfUmUmUmsGmsUm NO: 854 AAUGCCUUUGU NO: 302 ETX- UmsAfsAmUmAmCfAmAmCmAmUmGm SEQ ID UAAUACAACAUG SEQ ID S00003194 CmCfUmGfUmUfCmAmCmsAmsGm NO: 855 CCUGUUCACAG NO: 303 ETX- UmsGfsCmAmCmAfGmAmCmAmCmGm SEQ ID UGCACAGACACG SEQ ID S00003202 UmUfAmAfAmGfCmCmUmsUmsGm NO: 857 UUAAAGCCUUG NO: 305 ETX- GmsUfsUmCmCmUfUmUmGmCmGmCm SEQ ID GUUCCUUUGCGC SEQ ID S00003206 CmCfUmGfAmCfUmGmCmsAmsUm NO: 858 CCUGACUGCAU NO: 306 ETX- GmsUfsGmAmCmAfGmUmCmUmGmUm SEQ ID GUGACAGUCUGU SEQ ID S00003210 GmCfGmAfUmCfAmUmCmsCmsAm NO: 859 GCGAUCAUCCA NO: 307 ETX- AmsCfsCmAmCmGfCmAmGmUmCmUm SEQ ID ACCACGCAGUCU SEQ ID S00003214 AmUfAmAfUmGfCmCmUmsUmsUm NO: 860 AUAAUGCCUUU NO: 308 ETX- CmsAfsGmUmGmAfCmAmGmUmCmUm SEQ ID CAGUGACAGUCU SEQ ID S00003218 GmUfGmCfGmAfUmCmAmsUmsCm NO: 861 GUGCGAUCAUC NO: 309 ETX- UmsUfsGmGmGmAfAmUmAmCmGmGm SEQ ID UUGGGAAUACGG SEQ ID S00003222 AmCfCmAfCmGfCmAmGmsUmsCm NO: 862 ACCACGCAGUC NO: 310 ETX- GmsUfsCmUmAmUfAmAmUmGmCmCm SEQ ID GUCUAUAAUGCC SEQ ID S00003226 UmUfUmGfUmAfUmUmGmsCmsUm NO: 863 UUUGUAUUGCU NO: 311 ETX- UmsGfsUmGmCmGfAmUmCmAmUmCm SEQ ID UGUGCGAUCAUC SEQ ID S00003230 CmAfGmCfUmGfAmUmGmsAmsCm NO: 864 CAGCUGAUGAC NO: 312 ETX- AmsCfsGmGmAmCfCmAmCmGmCmAm SEQ ID ACGGACCACGCA SEQ ID S00003234 GmUfCmUfAmUfAmAmUmsGmsCm NO: 865 GUCUAUAAUGC NO: 313 ETX- UmsGfsCmUmAmGfAmCmGmGmGmUm SEQ ID UGCUAGACGGGU SEQ ID S00003238 AmCfGmGfGmCfAmAmAmsAmsUm NO: 866 ACGGGCAAAAU NO: 314 ETX- UmsCfsAmUmCmCfAmGmCmUmGmAm SEQ ID UCAUCCAGCUGA SEQ ID S00003242 UmGfAmCfGmAfUmGmUmsGmsAm NO: 867 UGACGAUGUGA NO: 315 ETX- CmsGfsGmGmUmAfCmGmGmGmCmAm SEQ ID CGGGUACGGGCA SEQ ID S00003246 AmAfAmUfCmAfAmGmAmsGmsGm NO: 868 AAAUCAAGAGG NO: 316 ETX- AmsAfsUmAmCmGfGmAmCmCmAmCm SEQ ID AAUACGGACCAC SEQ ID S00003250 GmCfAmGfUmCfUmAmUmsAmsAm NO: 869 GCAGUCUAUAA NO: 317 ETX- UmsCfsAmUmAmGfAmUmAmCmCmGm SEQ ID UCAUAGAUACCG SEQ ID S00003254 AmAfGmUfAmGfGmCmGmsGmsCm NO: 870 AAGUAGGCGGC NO: 318 ETX- GmsGfsGmAmAmUfAmCmGmGmAmCm SEQ ID GGGAAUACGGAC SEQ ID S00003258 CmAfCmGfCmAfGmUmCmsUmsAm NO: 871 CACGCAGUCUA NO: 319 ETX- GmsUfsGmCmGmAfUmCmAmUmCmCm SEQ ID GUGCGAUCAUCC SEQ ID S00003262 AmGfCmUfGmAfUmGmAmsCmsGm NO: 872 AGCUGAUGACG NO: 320 ETX- UmsAfsCmGmGmAfCmCmAmCmGmCm SEQ ID UACGGACCACGC SEQ ID S00003266 AmGfUmCfUmAfUmAmAmsUmsGm NO: 873 AGUCUAUAAUG NO: 321 ETX- UmsGfsUmCmAmUfAmGmAmUmAmCm SEQ ID UGUCAUAGAUAC SEQ ID S00003270 CmGfAmAfGmUfAmGmGmsCmsGm NO: 874 CGAAGUAGGCG NO: 322 ETX- UmsGfsCmGmAmUfCmAmUmCmCmAm SEQ ID UGCGAUCAUCCA SEQ ID S00003278 GmCfUmGfAmUfGmAmCmsGmsAm NO: 876 GCUGAUGACGA NO: 324 ETX- CmsUfsAmGmAmCfGmGmGmUmAmCm SEQ ID CUAGACGGGUAC SEQ ID S00003282 GmGfGmCfAmAfAmAmUmsCmsAm NO: 877 GGGCAAAAUCA NO: 325 ETX- GmsAfsUmCmCmGfGmAmAmGmCmAm SEQ ID GAUCCGGAAGCA SEQ ID S00003286 UmUfCmCfCmUfUmUmGmsCmsAm NO: 878 UUCCCUUUGCA NO: 326 ETX- GmsCfsAmCmAmGfAmCmAmCmGmUm SEQ ID GCACAGACACGU SEQ ID S00003290 UmAfAmAfGmCfCmUmUmsGmsGm NO: 879 UAAAGCCUUGG NO: 327 ETX- CmsCfsAmCmGmCfAmGmUmCmUmAm SEQ ID CCACGCAGUCUA SEQ ID S00003294 UmAfAmUfGmCfCmUmUmsUmsGm NO: 880 UAAUGCCUUUG NO: 328 ETX- GmsAfsCmGmGmGfUmAmCmGmGmGm SEQ ID GACGGGUACGGG SEQ ID S00003298 CmAfAmAfAmUfCmAmAmsGmsAm NO: 881 CAAAAUCAAGA NO: 329 ETX- GmsAfsUmAmCmCfGmAmAmGmUmAm SEQ ID GAUACCGAAGUA SEQ ID S00003302 GmGfCmGfGmCfUmCmGmsGmsUm NO: 882 GGCGGCUCGGU NO: 330 ETX- GmsUfsAmGmGmCfGmGmCmUmCmGm SEQ ID GUAGGCGGCUCG SEQ ID S00003306 GmUfAmGfAmUfGmAmUmsAmsAm NO: 883 GUAGAUGAUAA NO: 331 ETX- AmsGfsAmCmGmGfGmUmAmCmGmGm SEQ ID AGACGGGUACGG SEQ ID S00003310 GmCfAmAfAmAfUmCmAmsAmsGm NO: 884 GCAAAAUCAAG NO: 332 ETX- UmsAfsGmGmCmGfGmCmUmCmGmGm SEQ ID UAGGCGGCUCGG SEQ ID S00003314 UmAfGmAfUmGfAmUmAmsAmsUm NO: 885 UAGAUGAUAAU NO: 333 ETX- AmsAfsGmUmAmGfGmCmGmGmCmUm SEQ ID AAGUAGGCGGCU SEQ ID S00003318 CmGfGmUfAmGfAmUmGmsAmsUm NO: 886 CGGUAGAUGAU NO: 334 ETX- CmsUfsUmUmGmAfAmGmGmCmGmAm SEQ ID CUUUGAAGGCGA SEQ ID S00003322 AmGfUmUfAmAfGmAmGmsCmsCm NO: 887 AGUUAAGAGCC NO: 335 ETX- CmsGfsAmAmGmUfUmAmAmGmAmGm SEQ ID CGAAGUUAAGAG SEQ ID S00003326 CmCfUmGfGmGfUmGmGmsGmsGm NO: 888 CCUGGGUGGGG NO: 336 ETX- CmsCfsCmUmGmCfUmCmCmUmUmGm SEQ ID CCCUGCUCCUUG SEQ ID S00003330 GmGfAmAfUmAfCmGmGmsAmsCm NO: 889 GGAAUACGGAC NO: 337 ETX- GmsAfsAmGmGmAfCmAmGmAmAmCm SEQ ID GAAGGACAGAAC SEQ ID S00003334 UmCfCmCfUmGfCmUmCmsCmsUm NO: 890 UCCCUGCUCCU NO: 338 ETX- AmsGfsAmAmCmUfCmCmCmUmGmCm SEQ ID AGAACUCCCUGC SEQ ID S00003338 UmCfCmUfUmGfGmGmAmsAmsUm NO: 891 UCCUUGGGAAU NO: 339 ETX- CmsCfsUmGmCmUfCmCmUmUmGmGm SEQ ID CCUGCUCCUUGG SEQ ID S00003342 GmAfAmUfAmCfGmGmAmsCmsCm NO: 892 GAAUACGGACC NO: 340 ETX- CmsAfsGmAmAmGfGmAmCmAmGmAm SEQ ID CAGAAGGACAGA SEQ ID S00003346 AmCfUmCfCmCfUmGmCmsUmsCm NO: 893 ACUCCCUGCUC NO: 341 ETX- CmsUfsGmCmUmCfCmUmUmGmGmGm SEQ ID CUGCUCCUUGGG SEQ ID S00003350 AmAfUmAfCmGfGmAmCmsCmsAm NO: 894 AAUACGGACCA NO: 342 ETX- AmsGfsAmAmGmGfAmCmAmGmAmAm SEQ ID AGAAGGACAGAA SEQ ID S00003354 CmUfCmCfCmUfGmCmUmsCmsCm NO: 895 CUCCCUGCUCC NO: 343 ETX- AmsAfsGmGmAmCfAmGmAmAmCmUm SEQ ID AAGGACAGAACU SEQ ID S00003358 CmCfCmUfGmCfUmCmCmsUmsUm NO: 896 CCCUGCUCCUU NO: 344 ETX- 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UmsGfsGmUmAmCfAmGmGmCmCmCm SEQ ID UGGUACAGGCCC SEQ ID S00004142 UmUfAmAfUmCfCmCmAmsUmsCm NO: 1092 UUAAUCCCAUC NO: 540 ETX- GmsGfsCmGmGmCfUmCmGmGmUmAm SEQ ID GGCGGCUCGGUA SEQ ID S00004146 GmAfUmGfAmUfAmAmUmsAmsCm NO: 1093 GAUGAUAAUAC NO: 541 ETX- CmsGfsUmUmAmAfAmGmCmCmUmUm SEQ ID CGUUAAAGCCUU SEQ ID S00004150 GmGfUmAfCmAfGmGmCmsCmsCm NO: 1094 GGUACAGGCCC NO: 542 ETX- GmsGfsUmAmCmAfGmGmCmCmCmUm SEQ ID GGUACAGGCCCU SEQ ID S00004154 UmAfAmUfCmCfCmAmUmsCmsAm NO: 1095 UAAUCCCAUCA NO: 543 ETX- UmsAfsAmUmAmCfCmCmUmGmCmAm SEQ ID UAAUACCCUGCA SEQ ID S00004158 CmAfGmAfCmAfCmGmUmsUmsAm NO: 1096 CAGACACGUUA NO: 544 ETX- GmsAfsCmCmAmCfGmCmAmGmUmCm SEQ ID GACCACGCAGUC SEQ ID S00004162 UmAfUmAfAmUfGmCmCmsUmsUm NO: 1097 UAUAAUGCCUU NO: 545 ETX- GmsUfsUmAmAmGfAmGmCmCmUmGm SEQ ID GUUAAGAGCCUG SEQ ID S00004166 GmGfUmGfGmGfGmAmAmsGmsUm NO: 1098 GGUGGGGAAGU NO: 546 ETX- UmsGfsGmGmGmAfAmGmUmAmUmCm SEQ ID UGGGGAAGUAUC SEQ ID S00004170 UmGfAmUfGmAfCmAmUmsUmsGm NO: 1099 UGAUGACAUUG NO: 547 ETX- GmsGfsUmGmGmGfGmAmAmGmUmAm SEQ ID GGUGGGGAAGUA SEQ ID S00004174 UmCfUmGfAmUfGmAmCmsAmsUm NO: 1100 UCUGAUGACAU NO: 548 ETX- GmsUfsGmGmGmGfAmAmGmUmAmUm SEQ ID GUGGGGAAGUAU SEQ ID S00004178 CmUfGmAfUmGfAmCmAmsUmsUm NO: 1101 CUGAUGACAUU NO: 549 ETX- GmsGfsGmGmAmAfGmUmAmUmCmUm SEQ ID GGGGAAGUAUCU SEQ ID S00004182 GmAfUmGfAmCfAmUmUmsGmsGm NO: 1102 GAUGACAUUGG NO: 550 ETX- UmsUfsAmAmGmAfGmCmCmUmGmGm SEQ ID UUAAGAGCCUGG SEQ ID S00004186 GmUfGmGfGmGfAmAmGmsUmsAm NO: 1103 GUGGGGAAGUA NO: 551 ETX- CmsCfsGmAmAmGfUmAmGmGmCmGm SEQ ID CCGAAGUAGGCG SEQ ID S00004190 GmCfUmCfGmGfUmAmGmsAmsUm NO: 1104 GCUCGGUAGAU NO: 552 In certain embodiments, the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 1105-1380; wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises a nucleoside sequence of at least 19 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 1105-1380; wherein the second strand has a region of at least 85% complementarity over the 19 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises a nucleoside sequence of at least 21 contiguous nucleosides differing by 0 or 1 nucleosides from any one of SEQ ID NO: 1105-1380; wherein the second strand has a region of at least 85% complementarity over the 21 contiguous nucleosides to the first strand. In certain embodiments, the second strand comprises any one of SEQ ID NO: 1105-1380. The modification pattern of the nucleic acids as set forth in SEQ ID NO: 1105-1380 is summarized in Table 4 below. Table 4 provides the modified second (sense) sequences, together with the corresponding unmodified second (sense) sequences for siRNA oligonucleosides according to the present invention as follows. Table 4 Sense Modified Sense Strand SEQ ID Underlying Base SEQ ID strand ID NO (SS - Sequence NO (SS - 5’ ^ 3’ mod) unmod) 5’ ^ 3’ (Shown as an Unmodified Nucleotide Sequence) ETX- iaiaAmsUmsCmUmGmAmCmCmAfGfUfU SEQ ID AUCUGACCAGUUU SEQ ID S00003197 mUmUmCmUmCmUmUmAmAm NO: 1132 UCUCUUAA NO: 580 ETX- iaiaUmsUmsAmUmUmUmCmAmGfUfCfA SEQ ID UUAUUUCAGUCAC SEQ ID S00003273 mCmUmCmCmUmGmAmUmAm NO: 1151 UCCUGAUA NO: 599 ETX- iaiaAmsUmsCmUmAmUmGmAmCfAfCfU SEQ ID AUCUAUGACACUG SEQ ID S00003737 mGmCmAmAmAmGmGmGmAm NO: 1267 CAAAGGGA NO: 715 ETX- iaiaGmsUmsUmAmAmGmAmUmCfUfAfC SEQ ID GUUAAGAUCUACA SEQ ID S00003793 mAmAmAmUmCmUmGmAmUm NO: 1281 AAUCUGAU NO: 729 ETX- iaiaCmsGmsUmAmCmCmCmGmUfCfUfA SEQ ID CGUACCCGUCUAG SEQ ID S00003965 mGmCmAmGmCmUmGmAmUm NO: 1324 CAGCUGAU NO: 772 ETX- iaiaUmsAmsUmUmUmAmCmUmGfGfUfU SEQ ID UAUUUACUGGUUG SEQ ID S00003089 mGmAmAmAmAmUmGmGmGm NO: 1105 AAAAUGGG NO: 553 ETX- iaiaCmsAmsAmAmGmGmCmAmUfUfAfU SEQ ID CAAAGGCAUUAUA SEQ ID S00003093 mAmGmAmCmUmGmCmGmUm NO: 1106 GACUGCGU NO: 554 ETX- iaiaUmsGmsAmUmGmAmAmAmUfCfAfA SEQ ID UGAUGAAAUCAAG SEQ ID S00003097 mGmAmAmGmUmAmCmAmCm NO: 1107 AAGUACAC NO: 555 ETX- iaiaGmsAmsUmGmAmUmGmGmGfAfCfU SEQ ID GAUGAUGGGACUC SEQ ID S00003101 mCmAmAmUmUmGmUmAmUm NO: 1108 AAUUGUAU NO: 556 ETX- iaiaGmsCmsAmUmUmAmUmAmGfAfCfU SEQ ID GCAUUAUAGACUG SEQ ID S00003105 mGmCmGmUmGmGmUmCmCm NO: 1109 CGUGGUCC NO: 557 ETX- iaiaGmsUmsCmAmCmUmCmCmUfGfAfU SEQ ID GUCACUCCUGAUA SEQ ID S00003109 mAmAmAmUmAmAmCmAmAm NO: 1110 AAUAACAA NO: 558 ETX- iaiaAmsUmsAmCmAmAmAmGmGfCfAfU SEQ ID AUACAAAGGCAUU SEQ ID S00003113 mUmAmUmAmGmAmCmUmGm NO: 1111 AUAGACUG NO: 559 ETX- iaiaGmsCmsCmGmCmCmUmAmCfUfUfC SEQ ID GCCGCCUACUUCG SEQ ID S00003117 mGmGmUmAmUmCmUmAmUm NO: 1112 GUAUCUAU NO: 560 ETX- iaiaAmsGmsCmCmGmCmCmUmAfCfUfU SEQ ID AGCCGCCUACUUC SEQ ID S00003121 mCmGmGmUmAmUmCmUmAm NO: 1113 GGUAUCUA NO: 561 ETX- iaiaAmsGmsAmCmUmGmCmGmUfGfGfU SEQ ID AGACUGCGUGGUC SEQ ID S00003125 mCmCmGmUmAmUmUmCmCm NO: 1114 CGUAUUCC NO: 562 ETX- iaiaCmsAmsCmUmCmAmCmAmUfCfGfU SEQ ID CACUCACAUCGUC SEQ ID S00003129 mCmAmUmCmAmGmCmUmGm NO: 1115 AUCAGCUG NO: 563 ETX- iaiaAmsCmsUmUmCmGmCmCmUfUfCfA SEQ ID ACUUCGCCUUCAA SEQ ID S00003133 mAmAmGmAmUmAmAmAmUm NO: 1116 AGAUAAAU NO: 564 ETX- iaiaCmsUmsAmCmUmUmCmGmGfUfAfU SEQ ID CUACUUCGGUAUC SEQ ID S00003137 mCmUmAmUmGmAmCmAmCm NO: 1117 UAUGACAC NO: 565 ETX- iaiaUmsUmsUmAmCmUmGmGmUfUfGfA SEQ ID UUUACUGGUUGAA SEQ ID S00003141 mAmAmAmUmGmGmGmAmAm NO: 1118 AAUGGGAA NO: 566 ETX- iaiaUmsGmsCmCmCmGmUmAmCfCfCfG SEQ ID UGCCCGUACCCGU SEQ ID S00003145 mUmCmUmAmGmCmAmGmCm NO: 1119 CUAGCAGC NO: 567 ETX- iaiaAmsGmsUmCmAmGmGmGmCfGfCfA SEQ ID AGUCAGGGCGCAA SEQ ID S00003149 mAmAmGmGmAmAmCmUmGm NO: 1120 AGGAACUG NO: 568 ETX- iaiaUmsUmsAmCmUmGmGmUmUfGfAfA SEQ ID UUACUGGUUGAAA SEQ ID S00003153 mAmAmUmGmGmGmAmAmGm NO: 1121 AUGGGAAG NO: 569 ETX- iaiaGmsAmsGmCmCmGmCmCmUfAfCfU SEQ ID GAGCCGCCUACUU SEQ ID S00003157 mUmCmGmGmUmAmUmCmUm NO: 1122 CGGUAUCU NO: 570 ETX- iaiaCmsCmsUmCmGmGmUmGmAfCfUfG SEQ ID CCUCGGUGACUGC SEQ ID S00003161 mCmCmUmGmGmUmUmAmAm NO: 1123 CUGGUUAA NO: 571 ETX- iaiaCmsAmsUmCmGmUmCmAmUfCfAfG SEQ ID CAUCGUCAUCAGC SEQ ID S00003165 mCmUmGmGmAmUmGmAmUm NO: 1124 UGGAUGAU NO: 572 ETX- iaiaUmsUmsUmCmAmGmUmCmAfCfUfC SEQ ID UUUCAGUCACUCC SEQ ID S00003169 mCmUmGmAmUmAmAmAmUm NO: 1125 UGAUAAAU NO: 573 ETX- iaiaUmsGmsGmAmUmGmAmUmCfGfCfA SEQ ID UGGAUGAUCGCAC SEQ ID S00003173 mCmAmGmAmCmUmGmUmCm NO: 1126 AGACUGUC NO: 574 ETX- iaiaGmsCmsAmAmUmAmCmAmAfAfGfG SEQ ID GCAAUACAAAGGC SEQ ID S00003177 mCmAmUmUmAmUmAmGmAm NO: 1127 AUUAUAGA NO: 575 ETX- iaiaGmsCmsCmUmCmGmGmUmGfAfCfU SEQ ID GCCUCGGUGACUG SEQ ID S00003181 mGmCmCmUmGmGmUmUmAm NO: 1128 CCUGGUUA NO: 576 ETX- iaiaCmsUmsUmUmAmAmCmGmUfGfUfC SEQ ID CUUUAACGUGUCU SEQ ID S00003185 mUmGmUmGmCmAmGmGmGm NO: 1129 GUGCAGGG NO: 577 ETX- iaiaAmsAmsAmGmGmCmAmUmUfAfUfA SEQ ID AAAGGCAUUAUAG SEQ ID S00003189 mGmAmCmUmGmCmGmUmGm NO: 1130 ACUGCGUG NO: 578 ETX- iaiaGmsUmsGmAmAmCmAmGmGfCfAfU SEQ ID GUGAACAGGCAUG SEQ ID S00003193 mGmUmUmGmUmAmUmUmAm NO: 1131 UUGUAUUA NO: 579 ETX- iaiaAmsGmsGmCmUmUmUmAmAfCfGfU SEQ ID AGGCUUUAACGUG SEQ ID S00003201 mGmUmCmUmGmUmGmCmAm NO: 1133 UCUGUGCA NO: 581 ETX- iaiaGmsCmsAmGmUmCmAmGmGfGfCfG SEQ ID GCAGUCAGGGCGC SEQ ID S00003205 mCmAmAmAmGmGmAmAmCm NO: 1134 AAAGGAAC NO: 582 ETX- iaiaGmsAmsUmGmAmUmCmGmCfAfCfA SEQ ID GAUGAUCGCACAG SEQ ID S00003209 mGmAmCmUmGmUmCmAmCm NO: 1135 ACUGUCAC NO: 583 ETX- iaiaAmsGmsGmCmAmUmUmAmUfAfGfA SEQ ID AGGCAUUAUAGAC SEQ ID S00003213 mCmUmGmCmGmUmGmGmUm NO: 1136 UGCGUGGU NO: 584 ETX- iaiaUmsGmsAmUmCmGmCmAmCfAfGfA SEQ ID UGAUCGCACAGAC SEQ ID S00003217 mCmUmGmUmCmAmCmUmGm NO: 1137 UGUCACUG NO: 585 ETX- iaiaCmsUmsGmCmGmUmGmGmUfCfCfG SEQ ID CUGCGUGGUCCGU SEQ ID S00003221 mUmAmUmUmCmCmCmAmAm NO: 1138 AUUCCCAA NO: 586 ETX- iaiaCmsAmsAmUmAmCmAmAmAfGfGfC SEQ ID CAAUACAAAGGCA SEQ ID S00003225 mAmUmUmAmUmAmGmAmCm NO: 1139 UUAUAGAC NO: 587 ETX- iaiaCmsAmsUmCmAmGmCmUmGfGfAfU SEQ ID CAUCAGCUGGAUG SEQ ID S00003229 mGmAmUmCmGmCmAmCmAm NO: 1140 AUCGCACA NO: 588 ETX- iaiaAmsUmsUmAmUmAmGmAmCfUfGfC SEQ ID AUUAUAGACUGCG SEQ ID S00003233 mGmUmGmGmUmCmCmGmUm NO: 1141 UGGUCCGU NO: 589 ETX- iaiaUmsUmsUmGmCmCmCmGmUfAfCfC SEQ ID UUUGCCCGUACCC SEQ ID S00003237 mCmGmUmCmUmAmGmCmAm NO: 1142 GUCUAGCA NO: 590 ETX- iaiaAmsCmsAmUmCmGmUmCmAfUfCfA SEQ ID ACAUCGUCAUCAG SEQ ID S00003241 mGmCmUmGmGmAmUmGmAm NO: 1143 CUGGAUGA NO: 591 ETX- iaiaUmsCmsUmUmGmAmUmUmUfUfGfC SEQ ID UCUUGAUUUUGCC SEQ ID S00003245 mCmCmGmUmAmCmCmCmGm NO: 1144 CGUACCCG NO: 592 ETX- iaiaAmsUmsAmGmAmCmUmGmCfGfUfG SEQ ID AUAGACUGCGUGG SEQ ID S00003249 mGmUmCmCmGmUmAmUmUm NO: 1145 UCCGUAUU NO: 593 ETX- iaiaCmsGmsCmCmUmAmCmUmUfCfGfG SEQ ID CGCCUACUUCGGU SEQ ID S00003253 mUmAmUmCmUmAmUmGmAm NO: 1146 AUCUAUGA NO: 594 ETX- iaiaGmsAmsCmUmGmCmGmUmGfGfUfC SEQ ID GACUGCGUGGUCC SEQ ID S00003257 mCmGmUmAmUmUmCmCmCm NO: 1147 GUAUUCCC NO: 595 ETX- iaiaUmsCmsAmUmCmAmGmCmUfGfGfA SEQ ID UCAUCAGCUGGAU SEQ ID S00003261 mUmGmAmUmCmGmCmAmCm NO: 1148 GAUCGCAC NO: 596 ETX- iaiaUmsUmsAmUmAmGmAmCmUfGfCfG SEQ ID UUAUAGACUGCGU SEQ ID S00003265 mUmGmGmUmCmCmGmUmAm NO: 1149 GGUCCGUA NO: 597 ETX- iaiaCmsCmsUmAmCmUmUmCmGfGfUfA SEQ ID CCUACUUCGGUAU SEQ ID S00003269 mUmCmUmAmUmGmAmCmAm NO: 1150 CUAUGACA NO: 598 ETX- iaiaGmsUmsCmAmUmCmAmGmCfUfGfG SEQ ID GUCAUCAGCUGGA SEQ ID S00003277 mAmUmGmAmUmCmGmCmAm NO: 1152 UGAUCGCA NO: 600 ETX- iaiaAmsUmsUmUmUmGmCmCmCfGfUfA SEQ ID AUUUUGCCCGUAC SEQ ID S00003281 mCmCmCmGmUmCmUmAmGm NO: 1153 CCGUCUAG NO: 601 ETX- iaiaCmsAmsAmAmGmGmGmAmAfUfGfC SEQ ID CAAAGGGAAUGCU SEQ ID S00003285 mUmUmCmCmGmGmAmUmCm NO: 1154 UCCGGAUC NO: 602 ETX- iaiaAmsAmsGmGmCmUmUmUmAfAfCfG SEQ ID AAGGCUUUAACGU SEQ ID S00003289 mUmGmUmCmUmGmUmGmCm NO: 1155 GUCUGUGC NO: 603 ETX- iaiaAmsAmsGmGmCmAmUmUmAfUfAfG SEQ ID AAGGCAUUAUAGA SEQ ID S00003293 mAmCmUmGmCmGmUmGmGm NO: 1156 CUGCGUGG NO: 604 ETX- iaiaUmsUmsGmAmUmUmUmUmGfCfCfC SEQ ID UUGAUUUUGCCCG SEQ ID S00003297 mGmUmAmCmCmCmGmUmCm NO: 1157 UACCCGUC NO: 605 ETX- iaiaCmsGmsAmGmCmCmGmCmCfUfAfC SEQ ID CGAGCCGCCUACU SEQ ID S00003301 mUmUmCmGmGmUmAmUmCm NO: 1158 UCGGUAUC NO: 606 ETX- iaiaAmsUmsCmAmUmCmUmAmCfCfGfA SEQ ID AUCAUCUACCGAG SEQ ID S00003305 mGmCmCmGmCmCmUmAmCm NO: 1159 CCGCCUAC NO: 607 ETX- iaiaUmsGmsAmUmUmUmUmGmCfCfCfG SEQ ID UGAUUUUGCCCGU SEQ ID S00003309 mUmAmCmCmCmGmUmCmUm NO: 1160 ACCCGUCU NO: 608 ETX- iaiaUmsAmsUmCmAmUmCmUmAfCfCfG SEQ ID UAUCAUCUACCGA SEQ ID S00003313 mAmGmCmCmGmCmCmUmAm NO: 1161 GCCGCCUA NO: 609 ETX- iaiaCmsAmsUmCmUmAmCmCmGfAfGfC SEQ ID CAUCUACCGAGCC SEQ ID S00003317 mCmGmCmCmUmAmCmUmUm NO: 1162 GCCUACUU NO: 610 ETX- iaiaCmsUmsCmUmUmAmAmCmUfUfCfG SEQ ID CUCUUAACUUCGC SEQ ID S00003321 mCmCmUmUmCmAmAmAmGm NO: 1163 CUUCAAAG NO: 611 ETX- iaiaCmsCmsAmCmCmCmAmGmGfCfUfC SEQ ID CCACCCAGGCUCU SEQ ID S00003325 mUmUmAmAmCmUmUmCmGm NO: 1164 UAACUUCG NO: 612 ETX- iaiaCmsCmsGmUmAmUmUmCmCfCfAfA SEQ ID CCGUAUUCCCAAG SEQ ID S00003329 mGmGmAmGmCmAmGmGmGm NO: 1165 GAGCAGGG NO: 613 ETX- iaiaGmsAmsGmCmAmGmGmGmAfGfUfU SEQ ID GAGCAGGGAGUUC SEQ ID S00003333 mCmUmGmUmCmCmUmUmCm NO: 1166 UGUCCUUC NO: 614 ETX- iaiaUmsCmsCmCmAmAmGmGmAfGfCfA SEQ ID UCCCAAGGAGCAG SEQ ID S00003337 mGmGmGmAmGmUmUmCmUm NO: 1167 GGAGUUCU NO: 615 ETX- iaiaUmsCmsCmGmUmAmUmUmCfCfCfA SEQ ID UCCGUAUUCCCAA SEQ ID S00003341 mAmGmGmAmGmCmAmGmGm NO: 1168 GGAGCAGG NO: 616 ETX- iaiaGmsCmsAmGmGmGmAmGmUfUfCfU SEQ ID GCAGGGAGUUCUG SEQ ID S00003345 mGmUmCmCmUmUmCmUmGm NO: 1169 UCCUUCUG NO: 617 ETX- iaiaGmsUmsCmCmGmUmAmUmUfCfCfC SEQ ID GUCCGUAUUCCCA SEQ ID S00003349 mAmAmGmGmAmGmCmAmGm NO: 1170 AGGAGCAG NO: 618 ETX- iaiaAmsGmsCmAmGmGmGmAmGfUfUfC SEQ ID AGCAGGGAGUUCU SEQ ID S00003353 mUmGmUmCmCmUmUmCmUm NO: 1171 GUCCUUCU NO: 619 ETX- iaiaGmsGmsAmGmCmAmGmGmGfAfGfU SEQ ID GGAGCAGGGAGUU SEQ ID S00003357 mUmCmUmGmUmCmCmUmUm NO: 1172 CUGUCCUU NO: 620 ETX- iaiaUmsUmsCmCmCmAmAmGmGfAfGfC SEQ ID UUCCCAAGGAGCA SEQ ID S00003361 mAmGmGmGmAmGmUmUmCm NO: 1173 GGGAGUUC NO: 621 ETX- iaiaAmsGmsGmAmGmCmAmGmGfGfAfG SEQ ID AGGAGCAGGGAGU SEQ ID S00003365 mUmUmCmUmGmUmCmCmUm NO: 1174 UCUGUCCU NO: 622 ETX- iaiaCmsCmsCmAmCmCmCmAmGfGfCfU SEQ ID CCCACCCAGGCUC SEQ ID S00003369 mCmUmUmAmAmCmUmUmCm NO: 1175 UUAACUUC NO: 623 ETX- iaiaUmsCmsUmUmAmAmCmUmUfCfGfC SEQ ID UCUUAACUUCGCC SEQ ID S00003373 mCmUmUmCmAmAmAmGmAm NO: 1176 UUCAAAGA NO: 624 ETX- iaiaUmsUmsCmAmGmUmCmAmCfUfCfC SEQ ID UUCAGUCACUCCU SEQ ID S00003377 mUmGmAmUmAmAmAmUmAm NO: 1177 GAUAAAUA NO: 625 ETX- iaiaCmsAmsGmUmCmAmCmUmCfCfUfG SEQ ID CAGUCACUCCUGA SEQ ID S00003381 mAmUmAmAmAmUmAmAmCm NO: 1178 UAAAUAAC NO: 626 ETX- iaiaUmsCmsAmGmUmCmAmCmUfCfCfU SEQ ID UCAGUCACUCCUG SEQ ID S00003385 mGmAmUmAmAmAmUmAmAm NO: 1179 AUAAAUAA NO: 627 ETX- iaiaUmsGmsAmUmGmGmGmAmCfUfCfA SEQ ID UGAUGGGACUCAA SEQ ID S00003389 mAmUmUmGmUmAmUmUmUm NO: 1180 UUGUAUUU NO: 628 ETX- iaiaGmsAmsUmGmGmGmAmCmUfCfAfA SEQ ID GAUGGGACUCAAU SEQ ID S00003393 mUmUmGmUmAmUmUmUmUm NO: 1181 UGUAUUUU NO: 629 ETX- iaiaCmsAmsCmUmCmCmUmGmAfUfAfA SEQ ID CACUCCUGAUAAA SEQ ID S00003397 mAmUmAmAmCmAmAmAmUm NO: 1182 UAACAAAU NO: 630 ETX- iaiaAmsUmsUmCmAmUmCmUmGfAfCfC SEQ ID AUUCAUCUGACCA SEQ ID S00003401 mAmGmUmUmUmUmCmUmCm NO: 1183 GUUUUCUC NO: 631 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ETX- iaiaCmsCmsAmAmGmGmCmUmUfUfAfA SEQ ID CCAAGGCUUUAAC SEQ ID S00003813 mCmGmUmGmUmCmUmGmUm NO: 1286 GUGUCUGU NO: 734 ETX- iaiaUmsAmsUmUmCmAmUmCmUfGfAfC SEQ ID UAUUCAUCUGACC SEQ ID S00003817 mCmAmGmUmUmUmUmCmUm NO: 1287 AGUUUUCU NO: 735 ETX- iaiaAmsCmsUmGmCmCmUmGmGfUfUfA SEQ ID ACUGCCUGGUUAA SEQ ID S00003821 mAmGmAmUmCmUmAmCmAm NO: 1288 GAUCUACA NO: 736 ETX- iaiaGmsUmsUmGmAmCmUmUmCfCfUfA SEQ ID GUUGACUUCCUAU SEQ ID S00003825 mUmCmCmAmUmUmUmGmAm NO: 1289 CCAUUUGA NO: 737 ETX- iaiaUmsAmsUmGmAmCmAmCmUfGfCfA SEQ ID UAUGACACUGCAA SEQ ID S00003829 mAmAmGmGmGmAmAmUmGm NO: 1290 AGGGAAUG NO: 738 ETX- iaiaUmsUmsAmAmGmAmUmCmUfAfCfA SEQ ID UUAAGAUCUACAA SEQ ID S00003833 mAmAmUmCmUmGmAmUmGm NO: 1291 AUCUGAUG NO: 739 ETX- iaiaAmsGmsGmGmUmAmUmUmAfUfCfA SEQ ID AGGGUAUUAUCAU SEQ ID S00003837 mUmCmUmAmCmCmGmAmGm NO: 1292 CUACCGAG NO: 740 ETX- iaiaUmsGmsCmCmUmGmGmUmUfAfAfG SEQ ID UGCCUGGUUAAGA SEQ ID S00003841 mAmUmCmUmAmCmAmAmAm NO: 1293 UCUACAAA NO: 741 ETX- iaiaCmsUmsGmAmUmGmGmGmAfUfUfA SEQ ID CUGAUGGGAUUAA SEQ ID S00003845 mAmGmGmGmCmCmUmGmUm NO: 1294 GGGCCUGU NO: 742 ETX- iaiaGmsGmsUmAmUmCmUmAmUfGfAfC SEQ ID GGUAUCUAUGACA SEQ ID S00003849 mAmCmUmGmCmAmAmAmGm NO: 1295 CUGCAAAG NO: 743 ETX- iaiaAmsCmsCmCmGmUmCmUmAfGfCfA SEQ ID ACCCGUCUAGCAG SEQ ID S00003853 mGmCmUmGmAmUmGmUmGm NO: 1296 CUGAUGUG NO: 744 ETX- iaiaUmsAmsUmCmUmAmUmGmAfCfAfC SEQ ID UAUCUAUGACACU SEQ ID S00003857 mUmGmCmAmAmAmGmGmGm NO: 1297 GCAAAGGG NO: 745 ETX- iaiaCmsUmsGmAmUmGmUmGmGfGfUfA SEQ ID CUGAUGUGGGUAA SEQ ID S00003861 mAmAmGmCmUmGmGmAmGm NO: 1298 AGCUGGAG NO: 746 ETX- iaiaUmsCmsUmAmGmCmAmGmCfUfGfA SEQ ID UCUAGCAGCUGAU SEQ ID S00003865 mUmGmUmGmGmGmUmAmAm NO: 1299 GUGGGUAA NO: 747 ETX- iaiaGmsGmsGmCmCmUmGmUmAfCfCfA SEQ ID GGGCCUGUACCAA SEQ ID S00003869 mAmGmGmCmUmUmUmAmAm NO: 1300 GGCUUUAA NO: 748 ETX- iaiaCmsCmsCmGmUmAmCmCmCfGfUfC SEQ ID CCCGUACCCGUCU SEQ ID S00003873 mUmAmGmCmAmGmCmUmGm NO: 1301 AGCAGCUG NO: 749 ETX- iaiaCmsAmsGmCmUmGmAmUmGfUfGfG SEQ ID CAGCUGAUGUGGG SEQ ID S00003877 mGmUmAmAmAmGmCmUmGm NO: 1302 UAAAGCUG NO: 750 ETX- iaiaCmsCmsGmUmAmCmCmCmGfUfCfU SEQ ID CCGUACCCGUCUA SEQ ID S00003881 mAmGmCmAmGmCmUmGmAm NO: 1303 GCAGCUGA NO: 751 ETX- iaiaGmsCmsUmGmAmUmGmUmGfGfGfU SEQ ID GCUGAUGUGGGUA SEQ ID S00003885 mAmAmAmGmCmUmGmGmAm NO: 1304 AAGCUGGA NO: 752 ETX- iaiaGmsGmsUmAmUmUmAmUmCfAfUfC SEQ ID GGUAUUAUCAUCU SEQ ID S00003889 mUmAmCmCmGmAmGmCmCm NO: 1305 ACCGAGCC NO: 753 ETX- iaiaUmsUmsAmUmCmAmUmCmUfAfCfC SEQ ID UUAUCAUCUACCG SEQ ID S00003893 mGmAmGmCmCmGmCmCmUm NO: 1306 AGCCGCCU NO: 754 ETX- iaiaGmsUmsAmCmCmCmGmUmCfUfAfG SEQ ID GUACCCGUCUAGC SEQ ID S00003897 mCmAmGmCmUmGmAmUmGm NO: 1307 AGCUGAUG NO: 755 ETX- iaiaGmsAmsUmGmGmGmAmUmUfAfAf SEQ ID GAUGGGAUUAAGG SEQ ID S00003901 GmGmGmCmCmUmGmUmAmCm NO: 1308 GCCUGUAC NO: 756 ETX- iaiaGmsUmsCmUmGmUmGmCmAfGfGfG SEQ ID GUCUGUGCAGGGU SEQ ID S00003905 mUmAmUmUmAmUmCmAmUm NO: 1309 AUUAUCAU NO: 757 ETX- iaiaGmsCmsGmUmGmGmUmCmCfGfUfA SEQ ID GCGUGGUCCGUAU SEQ ID S00003909 mUmUmCmCmCmAmAmGmGm NO: 1310 UCCCAAGG NO: 758 ETX- iaiaCmsGmsUmGmGmUmCmCmGfUfAfU SEQ ID CGUGGUCCGUAUU SEQ ID S00003913 mUmCmCmCmAmAmGmGmAm NO: 1311 CCCAAGGA NO: 759 ETX- iaiaUmsGmsGmUmUmAmAmGmAfUfCfU SEQ ID UGGUUAAGAUCUA SEQ ID S00003917 mAmCmAmAmAmUmCmUmGm NO: 1312 CAAAUCUG NO: 760 ETX- iaiaAmsUmsGmAmUmGmAmAmAfUfCfA SEQ ID AUGAUGAAAUCAA SEQ ID S00003921 mAmGmAmAmGmUmAmCmAm NO: 1313 GAAGUACA NO: 761 ETX- iaiaGmsAmsUmCmUmAmCmAmAfAfUfC SEQ ID GAUCUACAAAUCU SEQ ID S00003925 mUmGmAmUmGmGmGmAmUm NO: 1314 GAUGGGAU NO: 762 ETX- iaiaGmsUmsGmCmAmGmGmGmUfAfUfU SEQ ID GUGCAGGGUAUUA SEQ ID S00003929 mAmUmCmAmUmCmUmAmCm NO: 1315 UCAUCUAC NO: 763 ETX- iaiaGmsUmsAmCmCmAmAmGmGfCfUfU SEQ ID GUACCAAGGCUUU SEQ ID S00003933 mUmAmAmCmGmUmGmUmCm NO: 1316 AACGUGUC NO: 764 ETX- iaiaGmsCmsAmGmCmUmGmAmUfGfUfG SEQ ID GCAGCUGAUGUGG SEQ ID S00003937 mGmGmUmAmAmAmGmCmUm NO: 1317 GUAAAGCU NO: 765 ETX- iaiaAmsUmsGmGmGmUmGmGmUfGfCfU SEQ ID AUGGGUGGUGCUU SEQ ID S00003941 mUmUmUmGmUmGmCmUmUm NO: 1318 UUGUGCUU NO: 766 ETX- iaiaCmsGmsGmUmGmAmCmUmGfCfCfU SEQ ID CGGUGACUGCCUG SEQ ID S00003945 mGmGmUmUmAmAmGmAmUm NO: 1319 GUUAAGAU NO: 767 ETX- iaiaCmsUmsAmGmCmAmGmCmUfGfAfU SEQ ID CUAGCAGCUGAUG SEQ ID S00003949 mGmUmGmGmGmUmAmAmAm NO: 1320 UGGGUAAA NO: 768 ETX- iaiaUmsAmsCmAmAmAmUmCmUfGfAfU SEQ ID UACAAAUCUGAUG SEQ ID S00003953 mGmGmGmAmUmUmAmAmGm NO: 1321 GGAUUAAG NO: 769 ETX- iaiaAmsCmsUmUmCmGmGmUmAfUfCfU SEQ ID ACUUCGGUAUCUA SEQ ID S00003957 mAmUmGmAmCmAmCmUmGm NO: 1322 UGACACUG NO: 770 ETX- iaiaAmsGmsCmUmGmAmUmGmUfGfGfG SEQ ID AGCUGAUGUGGGU SEQ ID S00003961 mUmAmAmAmGmCmUmGmGm NO: 1323 AAAGCUGG NO: 771 ETX- iaiaUmsCmsUmGmUmGmCmAmGfGfGfU SEQ ID UCUGUGCAGGGUA SEQ ID S00003969 mAmUmUmAmUmCmAmUmCm NO: 1325 UUAUCAUC NO: 773 ETX- iaiaUmsGmsCmUmUmGmUmCmUfUfGfU SEQ ID UGCUUGUCUUGUA SEQ ID S00003973 mAmUmGmAmUmGmAmAmAm NO: 1326 UGAUGAAA NO: 774 ETX- iaiaAmsCmsCmAmAmGmGmCmUfUfUfA SEQ ID ACCAAGGCUUUAA SEQ ID S00003977 mAmCmGmUmGmUmCmUmGm NO: 1327 CGUGUCUG NO: 775 ETX- iaiaGmsGmsGmUmGmCmAmUmGfGfUfC SEQ ID GGGUGCAUGGUCC SEQ ID S00003981 mCmAmAmUmGmUmUmCmUm NO: 1328 AAUGUUCU NO: 776 ETX- iaiaGmsAmsCmUmGmCmCmUmGfGfUfU SEQ ID GACUGCCUGGUUA SEQ ID S00003985 mAmAmGmAmUmCmUmAmCm NO: 1329 AGAUCUAC NO: 777 ETX- iaiaGmsAmsUmGmUmGmGmGmUfAfAf SEQ ID GAUGUGGGUAAAG SEQ ID S00003989 AmGmCmUmGmGmAmGmCmUm NO: 1330 CUGGAGCU NO: 778 ETX- iaiaUmsGmsGmUmCmCmGmUmAfUfUfC SEQ ID UGGUCCGUAUUCC SEQ ID S00003993 mCmCmAmAmGmGmAmGmCm NO: 1331 CAAGGAGC NO: 779 ETX- iaiaAmsCmsAmCmUmGmCmAmAfAfGfG SEQ ID ACACUGCAAAGGG SEQ ID S00003997 mGmAmAmUmGmCmUmUmCm NO: 1332 AAUGCUUC NO: 780 ETX- iaiaGmsAmsUmUmAmAmGmGmGfCfCfU SEQ ID GAUUAAGGGCCUG SEQ ID S00004001 mGmUmAmCmCmAmAmGmGm NO: 1333 UACCAAGG NO: 781 ETX- iaiaUmsGmsUmGmCmAmGmGmGfUfAfU SEQ ID UGUGCAGGGUAUU SEQ ID S00004005 mUmAmUmCmAmUmCmUmAm NO: 1334 AUCAUCUA NO: 782 ETX- iaiaAmsAmsCmGmUmGmUmCmUfGfUfG SEQ ID AACGUGUCUGUGC SEQ ID S00004009 mCmAmGmGmGmUmAmUmUm NO: 1335 AGGGUAUU NO: 783 ETX- iaiaGmsGmsCmCmUmGmUmAmCfCfAfA SEQ ID GGCCUGUACCAAG SEQ ID S00004013 mGmGmCmUmUmUmAmAmCm NO: 1336 GCUUUAAC NO: 784 ETX- iaiaUmsGmsAmCmAmCmUmGmCfAfAfA SEQ ID UGACACUGCAAAG SEQ ID S00004017 mGmGmGmAmAmUmGmCmUm NO: 1337 GGAAUGCU NO: 785 ETX- iaiaUmsCmsGmGmUmGmAmCmUfGfCfC SEQ ID UCGGUGACUGCCU SEQ ID S00004021 mUmGmGmUmUmAmAmGmAm NO: 1338 GGUUAAGA NO: 786 ETX- iaiaGmsCmsUmUmUmUmGmUmGfCfUfU SEQ ID GCUUUUGUGCUUG SEQ ID S00004025 mGmUmCmUmUmGmUmAmUm NO: 1339 UCUUGUAU NO: 787 ETX- iaiaGmsGmsUmGmGmUmGmCmUfUfUfU SEQ ID GGUGGUGCUUUUG SEQ ID S00004029 mGmUmGmCmUmUmGmUmCm NO: 1340 UGCUUGUC NO: 788 ETX- iaiaCmsGmsUmCmUmAmGmCmAfGfCfU SEQ ID CGUCUAGCAGCUG SEQ ID S00004033 mGmAmUmGmUmGmGmGmUm NO: 1341 AUGUGGGU NO: 789 ETX- iaiaAmsGmsGmGmCmCmUmGmUfAfCfC SEQ ID AGGGCCUGUACCA SEQ ID S00004037 mAmAmGmGmCmUmUmUmAm NO: 1342 AGGCUUUA NO: 790 ETX- iaiaGmsUmsGmCmUmUmGmUmCfUfUfG SEQ ID GUGCUUGUCUUGU SEQ ID S00004041 mUmAmUmGmAmUmGmAmAm NO: 1343 AUGAUGAA NO: 791 ETX- iaiaAmsAmsAmUmCmUmGmAmUfGfGfG SEQ ID AAAUCUGAUGGGA SEQ ID S00004045 mAmUmUmAmAmGmGmGmCm NO: 1344 UUAAGGGC NO: 792 ETX- iaiaCmsUmsAmCmAmAmAmUmCfUfGfA SEQ ID CUACAAAUCUGAU SEQ ID S00004049 mUmGmGmGmAmUmUmAmAm NO: 1345 GGGAUUAA NO: 793 ETX- iaiaCmsAmsGmGmGmUmAmUmUfAfUfC SEQ ID CAGGGUAUUAUCA SEQ ID S00004053 mAmUmCmUmAmCmCmGmAm NO: 1346 UCUACCGA NO: 794 ETX- iaiaCmsUmsGmUmAmCmCmAmAfGfGfC SEQ ID CUGUACCAAGGCU SEQ ID S00004057 mUmUmUmAmAmCmGmUmGm NO: 1347 UUAACGUG NO: 795 ETX- iaiaAmsGmsAmUmCmUmAmCmAfAfAfU SEQ ID AGAUCUACAAAUC SEQ ID S00004061 mCmUmGmAmUmGmGmGmAm NO: 1348 UGAUGGGA NO: 796 ETX- iaiaUmsUmsUmUmGmUmGmCmUfUfGfU SEQ ID UUUUGUGCUUGUC SEQ ID S00004065 mCmUmUmGmUmAmUmGmAm NO: 1349 UUGUAUGA NO: 797 ETX- iaiaAmsCmsAmAmAmUmCmUmGfAfUfG SEQ ID ACAAAUCUGAUGG SEQ ID S00004069 mGmGmAmUmUmAmAmGmGm NO: 1350 GAUUAAGG NO: 798 ETX- iaiaCmsAmsAmGmGmGmUmGmCfAfUfG SEQ ID CAAGGGUGCAUGG SEQ ID S00004073 mGmUmCmCmAmAmUmGmUm NO: 1351 UCCAAUGU NO: 799 ETX- iaiaGmsGmsAmUmUmAmAmGmGfGfCfC SEQ ID GGAUUAAGGGCCU SEQ ID S00004077 mUmGmUmAmCmCmAmAmGm NO: 1352 GUACCAAG NO: 800 ETX- iaiaUmsCmsGmGmUmAmUmCmUfAfUfG SEQ ID UCGGUAUCUAUGA SEQ ID S00004081 mAmCmAmCmUmGmCmAmAm NO: 1353 CACUGCAA NO: 801 ETX- iaiaCmsAmsAmGmGmCmUmUmUfAfAfC SEQ ID CAAGGCUUUAACG SEQ ID S00004085 mGmUmGmUmCmUmGmUmGm NO: 1354 UGUCUGUG NO: 802 ETX- iaiaCmsAmsUmGmGmGmUmGmGfUfGfC SEQ ID CAUGGGUGGUGCU SEQ ID S00004089 mUmUmUmUmGmUmGmCmUm NO: 1355 UUUGUGCU NO: 803 ETX- iaiaUmsAmsAmGmAmUmCmUmAfCfAfA SEQ ID UAAGAUCUACAAA SEQ ID S00004093 mAmUmCmUmGmAmUmGmGm NO: 1356 UCUGAUGG NO: 804 ETX- iaiaCmsCmsCmGmUmCmUmAmGfCfAfG SEQ ID CCCGUCUAGCAGC SEQ ID S00004097 mCmUmGmAmUmGmUmGmGm NO: 1357 UGAUGUGG NO: 805 ETX- iaiaAmsUmsGmAmCmAmCmUmGfCfAfA SEQ ID AUGACACUGCAAA SEQ ID S00004101 mAmGmGmGmAmAmUmGmCm NO: 1358 GGGAAUGC NO: 806 ETX- iaiaUmsAmsGmCmAmGmCmUmGfAfUfG SEQ ID UAGCAGCUGAUGU SEQ ID S00004105 mUmGmGmGmUmAmAmAmGm NO: 1359 GGGUAAAG NO: 807 ETX- iaiaGmsCmsAmAmAmGmGmGmAfAfUfG SEQ ID GCAAAGGGAAUGC SEQ ID S00004109 mCmUmUmCmCmGmGmAmUm NO: 1360 UUCCGGAU NO: 808 ETX- iaiaGmsCmsCmCmGmUmAmCmCfCfGfU SEQ ID GCCCGUACCCGUC SEQ ID S00004113 mCmUmAmGmCmAmGmCmUm NO: 1361 UAGCAGCU NO: 809 ETX- iaiaGmsUmsAmUmUmAmUmCmAfUfCfU SEQ ID GUAUUAUCAUCUA SEQ ID S00004117 mAmCmCmGmAmGmCmCmGm NO: 1362 CCGAGCCG NO: 810 ETX- iaiaCmsUmsCmUmUmGmAmUmUfUfUfG SEQ ID CUCUUGAUUUUGC SEQ ID S00004121 mCmCmCmGmUmAmCmCmCm NO: 1363 CCGUACCC NO: 811 ETX- iaiaUmsAmsCmCmCmGmUmCmUfAfGfC SEQ ID UACCCGUCUAGCA SEQ ID S00004125 mAmGmCmUmGmAmUmGmUm NO: 1364 GCUGAUGU NO: 812 ETX- iaiaCmsAmsAmAmUmCmUmGmAfUfGfG SEQ ID CAAAUCUGAUGGG SEQ ID S00004129 mGmAmUmUmAmAmGmGmGm NO: 1365 AUUAAGGG NO: 813 ETX- iaiaGmsUmsAmCmCmCmUmCmUfUfGfA SEQ ID GUACCCUCUUGAU SEQ ID S00004133 mUmUmUmUmGmCmCmCmGm NO: 1366 UUUGCCCG NO: 814 ETX- iaiaCmsCmsUmGmUmAmCmCmAfAfGfG SEQ ID CCUGUACCAAGGC SEQ ID S00004137 mCmUmUmUmAmAmCmGmUm NO: 1367 UUUAACGU NO: 815 ETX- iaiaUmsGmsGmGmAmUmUmAmAfGfGf SEQ ID UGGGAUUAAGGGC SEQ ID S00004141 GmCmCmUmGmUmAmCmCmAm NO: 1368 CUGUACCA NO: 816 ETX- iaiaAmsUmsUmAmUmCmAmUmCfUfAfC SEQ ID AUUAUCAUCUACC SEQ ID S00004145 mCmGmAmGmCmCmGmCmCm NO: 1369 GAGCCGCC NO: 817 ETX- iaiaGmsCmsCmUmGmUmAmCmCfAfAfG SEQ ID GCCUGUACCAAGG SEQ ID S00004149 mGmCmUmUmUmAmAmCmGm NO: 1370 CUUUAACG NO: 818 ETX- iaiaAmsUmsGmGmGmAmUmUmAfAfGf SEQ ID AUGGGAUUAAGGG SEQ ID S00004153 GmGmCmCmUmGmUmAmCmCm NO: 1371 CCUGUACC NO: 819 ETX- iaiaAmsCmsGmUmGmUmCmUmGfUfGfC SEQ ID ACGUGUCUGUGCA SEQ ID S00004157 mAmGmGmGmUmAmUmUmAm NO: 1372 GGGUAUUA NO: 820 ETX- iaiaGmsGmsCmAmUmUmAmUmAfGfAfC SEQ ID GGCAUUAUAGACU SEQ ID S00004161 mUmGmCmGmUmGmGmUmCm NO: 1373 GCGUGGUC NO: 821 ETX- iaiaUmsUmsCmCmCmCmAmCmCfCfAfG SEQ ID UUCCCCACCCAGG SEQ ID S00004165 mGmCmUmCmUmUmAmAmCm NO: 1374 CUCUUAAC NO: 822 ETX- iaiaAmsUmsGmUmCmAmUmCmAfGfAfU SEQ ID AUGUCAUCAGAUA SEQ ID S00004169 mAmCmUmUmCmCmCmCmAm NO: 1375 CUUCCCCA NO: 823 ETX- iaiaGmsUmsCmAmUmCmAmGmAfUfAfC SEQ ID GUCAUCAGAUACU SEQ ID S00004173 mUmUmCmCmCmCmAmCmCm NO: 1376 UCCCCACC NO: 824 ETX- iaiaUmsGmsUmCmAmUmCmAmGfAfUfA SEQ ID UGUCAUCAGAUAC SEQ ID S00004177 mCmUmUmCmCmCmCmAmCm NO: 1377 UUCCCCAC NO: 825 ETX- iaiaAmsAmsUmGmUmCmAmUmCfAfGfA SEQ ID AAUGUCAUCAGAU SEQ ID S00004181 mUmAmCmUmUmCmCmCmCm NO: 1378 ACUUCCCC NO: 826 ETX- iaiaCmsUmsUmCmCmCmCmAmCfCfCfA SEQ ID CUUCCCCACCCAG SEQ ID S00004185 mGmGmCmUmCmUmUmAmAm NO: 1379 GCUCUUAA NO: 827 ETX- iaiaCmsUmsAmCmCmGmAmGmCfCfGfC SEQ ID CUACCGAGCCGCC SEQ ID S00004189 mCmUmAmCmUmUmCmGmGm NO: 1380 UACUUCGG NO: 828 As used herein, and in particular in Tables 3 and 4, the following abbreviations are used for modified nucleosides: A – adenosine C – cytidine G – guanosine T – thymidine m – 2’-O-methyl f – 2’fluro s – phosphorothioate bond o - thermally destabilised nucleoside ia - inverted abasic nucleoside Am stands for 2'-O-methyl-adenosine, Cm stands for 2'-O-methyl-cytidine, Gm stands for 2'-O- methyl-guanosine, Um stands for 2'-O-methyl-uridine, Af stands for 2'-Fluoro-adenosine, Cf stands for 2'-Fluoro-cytidine, Gf stands for 2'-Fluoro-guanosine and Uf stands for 2'-Fluoro- uridine. Furthermore, the letter “s” is used as abbreviation for a phosphorothioate linkage between two consecutive (modified) nucleosides. For example, the abbreviation “AmsAm” is used for two consecutive 2'-O-methyl-adenosine nucleosides that are linked via a 3’5’ phosphorothioate linkage. No abbreviation is used for nucleosides that are linked via a standard 3’5’ phosphodiester linkage. For example, the abbreviation “AmAm” is used for two consecutive 2'- O-methyl-adenosine nucleosides that are linked via a 3’5’ phosphodiester linkage. Some of the modified second strand sequences as illustrated above in Table 4 include the preferred 5’ iaia motif. However, it should also be understood that the scope of these modified second strand sequences additionally includes the Me / F modified second strand in the absence of the 5’iaia motif. In certain embodiments, the nucleic acid comprises a first strand that comprises, consists of, or consists essentially of a (modified) nucleoside sequence differing by 0 or 1 nucleosides from any one of SEQ ID NO: 829-1104; and a second strand that comprises, consists of, or consists essentially of a (modified) nucleoside sequence differing by 0 or 1 nucleosides from any one of SEQ ID NO:1105-1380. Preferred combinations of complementary modified antisense (first) and sense (second) strands are listed below in Table 5. Table 5 identifies duplexes with Duplex IDs referencing the modified antisense and sense IDs from previous Tables 3 and 4. Table 5 Duplex ID First (Antisense) strand ID Second (Sense) strand ID ETX-M00001351 ETX-S00003090 ETX-S00003089 ETX-M00001352 ETX-S00003094 ETX-S00003093 ETX-M00001353 ETX-S00003098 ETX-S00003097 ETX-M00001354 ETX-S00003102 ETX-S00003101 ETX-M00001355 ETX-S00003106 ETX-S00003105 ETX-M00001356 ETX-S00003110 ETX-S00003109 ETX-M00001357 ETX-S00003114 ETX-S00003113 ETX-M00001358 ETX-S00003118 ETX-S00003117 ETX-M00001359 ETX-S00003122 ETX-S00003121 ETX-M00001360 ETX-S00003126 ETX-S00003125 ETX-M00001361 ETX-S00003130 ETX-S00003129 ETX-M00001362 ETX-S00003134 ETX-S00003133 ETX-M00001363 ETX-S00003138 ETX-S00003137 ETX-M00001364 ETX-S00003142 ETX-S00003141 ETX-M00001365 ETX-S00003146 ETX-S00003145 ETX-M00001366 ETX-S00003150 ETX-S00003149 ETX-M00001367 ETX-S00003154 ETX-S00003153 ETX-M00001368 ETX-S00003158 ETX-S00003157 ETX-M00001369 ETX-S00003162 ETX-S00003161 ETX-M00001370 ETX-S00003166 ETX-S00003165 ETX-M00001371 ETX-S00003170 ETX-S00003169 ETX-M00001372 ETX-S00003174 ETX-S00003173 ETX-M00001373 ETX-S00003178 ETX-S00003177 ETX-M00001374 ETX-S00003182 ETX-S00003181 ETX-M00001375 ETX-S00003186 ETX-S00003185 ETX-M00001376 ETX-S00003190 ETX-S00003189 ETX-M00001377 ETX-S00003194 ETX-S00003193 ETX-M00001378 ETX-S00003198 ETX-S00003197 ETX-M00001379 ETX-S00003202 ETX-S00003201 ETX-M00001380 ETX-S00003206 ETX-S00003205 ETX-M00001381 ETX-S00003210 ETX-S00003209 ETX-M00001382 ETX-S00003214 ETX-S00003213 ETX-M00001383 ETX-S00003218 ETX-S00003217 ETX-M00001384 ETX-S00003222 ETX-S00003221 ETX-M00001385 ETX-S00003226 ETX-S00003225 ETX-M00001386 ETX-S00003230 ETX-S00003229 ETX-M00001387 ETX-S00003234 ETX-S00003233 ETX-M00001388 ETX-S00003238 ETX-S00003237 ETX-M00001389 ETX-S00003242 ETX-S00003241 ETX-M00001390 ETX-S00003246 ETX-S00003245 ETX-M00001391 ETX-S00003250 ETX-S00003249 ETX-M00001392 ETX-S00003254 ETX-S00003253 ETX-M00001393 ETX-S00003258 ETX-S00003257 ETX-M00001394 ETX-S00003262 ETX-S00003261 ETX-M00001395 ETX-S00003266 ETX-S00003265 ETX-M00001396 ETX-S00003270 ETX-S00003269 ETX-M00001397 ETX-S00003274 ETX-S00003273 ETX-M00001398 ETX-S00003278 ETX-S00003277 ETX-M00001399 ETX-S00003282 ETX-S00003281 ETX-M00001400 ETX-S00003286 ETX-S00003285 ETX-M00001401 ETX-S00003290 ETX-S00003289 ETX-M00001402 ETX-S00003294 ETX-S00003293 ETX-M00001403 ETX-S00003298 ETX-S00003297 ETX-M00001404 ETX-S00003302 ETX-S00003301 ETX-M00001405 ETX-S00003306 ETX-S00003305 ETX-M00001406 ETX-S00003310 ETX-S00003309 ETX-M00001407 ETX-S00003314 ETX-S00003313 ETX-M00001408 ETX-S00003318 ETX-S00003317 ETX-M00001409 ETX-S00003322 ETX-S00003321 ETX-M00001410 ETX-S00003326 ETX-S00003325 ETX-M00001411 ETX-S00003330 ETX-S00003329 ETX-M00001412 ETX-S00003334 ETX-S00003333 ETX-M00001413 ETX-S00003338 ETX-S00003337 ETX-M00001414 ETX-S00003342 ETX-S00003341 ETX-M00001415 ETX-S00003346 ETX-S00003345 ETX-M00001416 ETX-S00003350 ETX-S00003349 ETX-M00001417 ETX-S00003354 ETX-S00003353 ETX-M00001418 ETX-S00003358 ETX-S00003357 ETX-M00001419 ETX-S00003362 ETX-S00003361 ETX-M00001420 ETX-S00003366 ETX-S00003365 ETX-M00001421 ETX-S00003370 ETX-S00003369 ETX-M00001422 ETX-S00003374 ETX-S00003373 ETX-M00001423 ETX-S00003378 ETX-S00003377 ETX-M00001424 ETX-S00003382 ETX-S00003381 ETX-M00001425 ETX-S00003386 ETX-S00003385 ETX-M00001426 ETX-S00003390 ETX-S00003389 ETX-M00001427 ETX-S00003394 ETX-S00003393 ETX-M00001428 ETX-S00003398 ETX-S00003397 ETX-M00001429 ETX-S00003402 ETX-S00003401 ETX-M00001430 ETX-S00003406 ETX-S00003405 ETX-M00001431 ETX-S00003410 ETX-S00003409 ETX-M00001432 ETX-S00003414 ETX-S00003413 ETX-M00001433 ETX-S00003418 ETX-S00003417 ETX-M00001434 ETX-S00003422 ETX-S00003421 ETX-M00001435 ETX-S00003426 ETX-S00003425 ETX-M00001436 ETX-S00003430 ETX-S00003429 ETX-M00001437 ETX-S00003434 ETX-S00003433 ETX-M00001438 ETX-S00003438 ETX-S00003437 ETX-M00001439 ETX-S00003442 ETX-S00003441 ETX-M00001440 ETX-S00003446 ETX-S00003445 ETX-M00001441 ETX-S00003450 ETX-S00003449 ETX-M00001442 ETX-S00003454 ETX-S00003453 ETX-M00001443 ETX-S00003458 ETX-S00003457 ETX-M00001444 ETX-S00003462 ETX-S00003461 ETX-M00001445 ETX-S00003466 ETX-S00003465 ETX-M00001446 ETX-S00003470 ETX-S00003469 ETX-M00001447 ETX-S00003474 ETX-S00003473 ETX-M00001448 ETX-S00003478 ETX-S00003477 ETX-M00001449 ETX-S00003482 ETX-S00003481 ETX-M00001450 ETX-S00003486 ETX-S00003485 ETX-M00001451 ETX-S00003490 ETX-S00003489 ETX-M00001452 ETX-S00003494 ETX-S00003493 ETX-M00001453 ETX-S00003498 ETX-S00003497 ETX-M00001454 ETX-S00003502 ETX-S00003501 ETX-M00001455 ETX-S00003506 ETX-S00003505 ETX-M00001456 ETX-S00003510 ETX-S00003509 ETX-M00001457 ETX-S00003514 ETX-S00003513 ETX-M00001458 ETX-S00003518 ETX-S00003517 ETX-M00001459 ETX-S00003522 ETX-S00003521 ETX-M00001460 ETX-S00003526 ETX-S00003525 ETX-M00001461 ETX-S00003530 ETX-S00003529 ETX-M00001462 ETX-S00003534 ETX-S00003533 ETX-M00001463 ETX-S00003538 ETX-S00003537 ETX-M00001464 ETX-S00003542 ETX-S00003541 ETX-M00001465 ETX-S00003546 ETX-S00003545 ETX-M00001466 ETX-S00003550 ETX-S00003549 ETX-M00001467 ETX-S00003554 ETX-S00003553 ETX-M00001468 ETX-S00003558 ETX-S00003557 ETX-M00001469 ETX-S00003562 ETX-S00003561 ETX-M00001470 ETX-S00003566 ETX-S00003565 ETX-M00001471 ETX-S00003570 ETX-S00003569 ETX-M00001472 ETX-S00003574 ETX-S00003573 ETX-M00001473 ETX-S00003578 ETX-S00003577 ETX-M00001474 ETX-S00003582 ETX-S00003581 ETX-M00001475 ETX-S00003586 ETX-S00003585 ETX-M00001476 ETX-S00003590 ETX-S00003589 ETX-M00001477 ETX-S00003594 ETX-S00003593 ETX-M00001478 ETX-S00003598 ETX-S00003597 ETX-M00001479 ETX-S00003602 ETX-S00003601 ETX-M00001480 ETX-S00003606 ETX-S00003605 ETX-M00001481 ETX-S00003610 ETX-S00003609 ETX-M00001482 ETX-S00003614 ETX-S00003613 ETX-M00001483 ETX-S00003618 ETX-S00003617 ETX-M00001484 ETX-S00003622 ETX-S00003621 ETX-M00001485 ETX-S00003626 ETX-S00003625 ETX-M00001486 ETX-S00003630 ETX-S00003629 ETX-M00001487 ETX-S00003634 ETX-S00003633 ETX-M00001488 ETX-S00003638 ETX-S00003637 ETX-M00001489 ETX-S00003642 ETX-S00003641 ETX-M00001490 ETX-S00003646 ETX-S00003645 ETX-M00001491 ETX-S00003650 ETX-S00003649 ETX-M00001492 ETX-S00003654 ETX-S00003653 ETX-M00001493 ETX-S00003658 ETX-S00003657 ETX-M00001494 ETX-S00003662 ETX-S00003661 ETX-M00001495 ETX-S00003666 ETX-S00003665 ETX-M00001496 ETX-S00003670 ETX-S00003669 ETX-M00001497 ETX-S00003674 ETX-S00003673 ETX-M00001498 ETX-S00003678 ETX-S00003677 ETX-M00001499 ETX-S00003682 ETX-S00003681 ETX-M00001500 ETX-S00003686 ETX-S00003685 ETX-M00001501 ETX-S00003690 ETX-S00003689 ETX-M00001502 ETX-S00003694 ETX-S00003693 ETX-M00001503 ETX-S00003698 ETX-S00003697 ETX-M00001504 ETX-S00003702 ETX-S00003701 ETX-M00001505 ETX-S00003706 ETX-S00003705 ETX-M00001506 ETX-S00003710 ETX-S00003709 ETX-M00001507 ETX-S00003714 ETX-S00003713 ETX-M00001508 ETX-S00003718 ETX-S00003717 ETX-M00001509 ETX-S00003722 ETX-S00003721 ETX-M00001510 ETX-S00003726 ETX-S00003725 ETX-M00001511 ETX-S00003730 ETX-S00003729 ETX-M00001512 ETX-S00003734 ETX-S00003733 ETX-M00001513 ETX-S00003738 ETX-S00003737 ETX-M00001514 ETX-S00003742 ETX-S00003741 ETX-M00001515 ETX-S00003746 ETX-S00003745 ETX-M00001516 ETX-S00003750 ETX-S00003749 ETX-M00001517 ETX-S00003754 ETX-S00003753 ETX-M00001518 ETX-S00003758 ETX-S00003757 ETX-M00001519 ETX-S00003762 ETX-S00003761 ETX-M00001520 ETX-S00003766 ETX-S00003765 ETX-M00001521 ETX-S00003770 ETX-S00003769 ETX-M00001522 ETX-S00003774 ETX-S00003773 ETX-M00001523 ETX-S00003778 ETX-S00003777 ETX-M00001524 ETX-S00003782 ETX-S00003781 ETX-M00001525 ETX-S00003786 ETX-S00003785 ETX-M00001526 ETX-S00003790 ETX-S00003789 ETX-M00001527 ETX-S00003794 ETX-S00003793 ETX-M00001528 ETX-S00003798 ETX-S00003797 ETX-M00001529 ETX-S00003802 ETX-S00003801 ETX-M00001530 ETX-S00003806 ETX-S00003805 ETX-M00001531 ETX-S00003810 ETX-S00003809 ETX-M00001532 ETX-S00003814 ETX-S00003813 ETX-M00001533 ETX-S00003818 ETX-S00003817 ETX-M00001534 ETX-S00003822 ETX-S00003821 ETX-M00001535 ETX-S00003826 ETX-S00003825 ETX-M00001536 ETX-S00003830 ETX-S00003829 ETX-M00001537 ETX-S00003834 ETX-S00003833 ETX-M00001538 ETX-S00003838 ETX-S00003837 ETX-M00001539 ETX-S00003842 ETX-S00003841 ETX-M00001540 ETX-S00003846 ETX-S00003845 ETX-M00001541 ETX-S00003850 ETX-S00003849 ETX-M00001542 ETX-S00003854 ETX-S00003853 ETX-M00001543 ETX-S00003858 ETX-S00003857 ETX-M00001544 ETX-S00003862 ETX-S00003861 ETX-M00001545 ETX-S00003866 ETX-S00003865 ETX-M00001546 ETX-S00003870 ETX-S00003869 ETX-M00001547 ETX-S00003874 ETX-S00003873 ETX-M00001548 ETX-S00003878 ETX-S00003877 ETX-M00001549 ETX-S00003882 ETX-S00003881 ETX-M00001550 ETX-S00003886 ETX-S00003885 ETX-M00001551 ETX-S00003890 ETX-S00003889 ETX-M00001552 ETX-S00003894 ETX-S00003893 ETX-M00001553 ETX-S00003898 ETX-S00003897 ETX-M00001554 ETX-S00003902 ETX-S00003901 ETX-M00001555 ETX-S00003906 ETX-S00003905 ETX-M00001556 ETX-S00003910 ETX-S00003909 ETX-M00001557 ETX-S00003914 ETX-S00003913 ETX-M00001558 ETX-S00003918 ETX-S00003917 ETX-M00001559 ETX-S00003922 ETX-S00003921 ETX-M00001560 ETX-S00003926 ETX-S00003925 ETX-M00001561 ETX-S00003930 ETX-S00003929 ETX-M00001562 ETX-S00003934 ETX-S00003933 ETX-M00001563 ETX-S00003938 ETX-S00003937 ETX-M00001564 ETX-S00003942 ETX-S00003941 ETX-M00001565 ETX-S00003946 ETX-S00003945 ETX-M00001566 ETX-S00003950 ETX-S00003949 ETX-M00001567 ETX-S00003954 ETX-S00003953 ETX-M00001568 ETX-S00003958 ETX-S00003957 ETX-M00001569 ETX-S00003962 ETX-S00003961 ETX-M00001570 ETX-S00003966 ETX-S00003965 ETX-M00001571 ETX-S00003970 ETX-S00003969 ETX-M00001572 ETX-S00003974 ETX-S00003973 ETX-M00001573 ETX-S00003978 ETX-S00003977 ETX-M00001574 ETX-S00003982 ETX-S00003981 ETX-M00001575 ETX-S00003986 ETX-S00003985 ETX-M00001576 ETX-S00003990 ETX-S00003989 ETX-M00001577 ETX-S00003994 ETX-S00003993 ETX-M00001578 ETX-S00003998 ETX-S00003997 ETX-M00001579 ETX-S00004002 ETX-S00004001 ETX-M00001580 ETX-S00004006 ETX-S00004005 ETX-M00001581 ETX-S00004010 ETX-S00004009 ETX-M00001582 ETX-S00004014 ETX-S00004013 ETX-M00001583 ETX-S00004018 ETX-S00004017 ETX-M00001584 ETX-S00004022 ETX-S00004021 ETX-M00001585 ETX-S00004026 ETX-S00004025 ETX-M00001586 ETX-S00004030 ETX-S00004029 ETX-M00001587 ETX-S00004034 ETX-S00004033 ETX-M00001588 ETX-S00004038 ETX-S00004037 ETX-M00001589 ETX-S00004042 ETX-S00004041 ETX-M00001590 ETX-S00004046 ETX-S00004045 ETX-M00001591 ETX-S00004050 ETX-S00004049 ETX-M00001592 ETX-S00004054 ETX-S00004053 ETX-M00001593 ETX-S00004058 ETX-S00004057 ETX-M00001594 ETX-S00004062 ETX-S00004061 ETX-M00001595 ETX-S00004066 ETX-S00004065 ETX-M00001596 ETX-S00004070 ETX-S00004069 ETX-M00001597 ETX-S00004074 ETX-S00004073 ETX-M00001598 ETX-S00004078 ETX-S00004077 ETX-M00001599 ETX-S00004082 ETX-S00004081 ETX-M00001600 ETX-S00004086 ETX-S00004085 ETX-M00001601 ETX-S00004090 ETX-S00004089 ETX-M00001602 ETX-S00004094 ETX-S00004093 ETX-M00001603 ETX-S00004098 ETX-S00004097 ETX-M00001604 ETX-S00004102 ETX-S00004101 ETX-M00001605 ETX-S00004106 ETX-S00004105 ETX-M00001606 ETX-S00004110 ETX-S00004109 ETX-M00001607 ETX-S00004114 ETX-S00004113 ETX-M00001608 ETX-S00004118 ETX-S00004117 ETX-M00001609 ETX-S00004122 ETX-S00004121 ETX-M00001610 ETX-S00004126 ETX-S00004125 ETX-M00001611 ETX-S00004130 ETX-S00004129 ETX-M00001612 ETX-S00004134 ETX-S00004133 ETX-M00001613 ETX-S00004138 ETX-S00004137 ETX-M00001614 ETX-S00004142 ETX-S00004141 ETX-M00001615 ETX-S00004146 ETX-S00004145 ETX-M00001616 ETX-S00004150 ETX-S00004149 ETX-M00001617 ETX-S00004154 ETX-S00004153 ETX-M00001618 ETX-S00004158 ETX-S00004157 ETX-M00001619 ETX-S00004162 ETX-S00004161 ETX-M00001620 ETX-S00004166 ETX-S00004165 ETX-M00001621 ETX-S00004170 ETX-S00004169 ETX-M00001622 ETX-S00004174 ETX-S00004173 ETX-M00001623 ETX-S00004178 ETX-S00004177 ETX-M00001624 ETX-S00004182 ETX-S00004181 ETX-M00001625 ETX-S00004186 ETX-S00004185 ETX-M00001626 ETX-S00004190 ETX-S00004189 For duplexes of Table 5: ETX-M00001351 – ETX-M00001626 preferably have a duplex structure according to Figure 8b. In a particularly preferred embodiment, the invention relates to a nucleic acid comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following first and second sequences: Duplex ID Modified first strand Modified second strand ETX-S00003198 ETX-S00003197 ETX-M00001378 (SEQ ID NO: 856) (SEQ ID NO: 1132) ETX-M00001397 ETX-S00003274 ETX-S00003273 (SEQ ID NO: 875) (SEQ ID NO: 1151) ETX-M00001513 ETX-S00003738 ETX-S00003737 (SEQ ID NO: 991) (SEQ ID NO: 1267) ETX-M00001527 ETX-S00003794 ETX-S00003793 (SEQ ID NO: 1005) (SEQ ID NO: 1281) ETX-M00001570 ETX-S00003966 ETX-S00003965 (SEQ ID NO: 1048) (SEQ ID NO: 1324) In an even more preferred embodiment, the invention relates to a nucleic acid comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following first and second sequences: Duplex ID Modified first strand Modified second strand ETX-S00003198 ETX-S00003197 ETX-M00001378 (SEQ ID NO: 856) (SEQ ID NO: 1132) In case of ambiguity between the sequences in this specification and the sequences in the attached sequence listing, the sequences provided herein are considered to be the correct sequences. ABASIC NUCLEOTIDES In certain embodiments, there are 1, e.g.2, e.g.3, e.g.4 or more abasic nucleosides present in nucleic acids according to the invention. Abasic nucleosides are modified nucleosides because they lack the base normally seen at position 1 of the sugar moiety. Typically, there will be a hydrogen at position 1 of the sugar moiety of the abasic nucleosides present in a nucleic acid according to the present invention. The abasic nucleosides are in the terminal region of the second strand, preferably located within the terminal 5 nucleosides of the end of the strand. The terminal region may be the terminal 5 nucleosides, which includes abasic nucleosides. The second strand may comprise, as preferred features (which are all specifically contemplated in combination unless mutually exclusive): 2, or more than 2, abasic nucleosides in a terminal region of the second strand; and/or 2, or more than 2, abasic nucleosides in either the 5’ or 3’ terminal region of the second strand; and/or 2, or more than 2, abasic nucleosides in either the 5’ or 3’ terminal region of the second strand, wherein the abasic nucleosides are present in an overhang as herein described; and/or 2, or more than 2, consecutive abasic nucleosides in a terminal region of the second strand, wherein preferably one such abasic nucleosides is a terminal nucleosides; and/or 2, or more than 2, consecutive abasic nucleosides in either the 5’ or 3’ terminal region of the second strand, wherein preferably one such abasic nucleosides is a terminal nucleosides in either the 5’ or 3’ terminal region of the second strand; and/or a reversed internucleoside linkage connects at least one abasic nucleoside to an adjacent basic nucleoside in a terminal region of the second strand; and/or a reversed internucleoside linkage connects at least one abasic nucleoside to an adjacent basic nucleoside in either the 5’ or 3’ terminal region of the second strand; and/or an abasic nucleoside as the penultimate nucleoside which is connected via the reversed linkage to the nucleoside which is not the terminal nucleoside (called the antepenultimate nucleoside herein); and/or abasic nucleosides as the 2 terminal nucleosides connected via a 5’-3’ linkage when reading the strand in the direction towards the terminus comprising the terminal nucleosides; abasic nucleosides as the 2 terminal nucleosides connected via a 3’-5’ linkage when reading the strand in the direction towards the terminus comprising the terminal nucleosides; abasic nucleosides as the terminal 2 positions, wherein the penultimate nucleoside is connected via the reversed linkage to the antepenultimate nucleoside, and wherein the reversed linkage is a 5-5’ reversed linkage or a 3’-3’ reversed linkage; abasic nucleosides as the terminal 2 positions, wherein the penultimate nucleoside is connected via the reversed linkage to the antepenultimate nucleoside, and wherein either (1) the reversed linkage is a 5-5’ reversed linkage and the linkage between the terminal and penultimate abasic nucleosides is 3’5’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides; or (2) the reversed linkage is a 3-3’ reversed linkage and the linkage between the terminal and penultimate abasic nucleosides is 5’3’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides. Preferably there is an abasic nucleoside at the terminus of the second strand. Preferably there are 2 or at least 2 abasic nucleosides in the terminal region of the second strand, preferably at the terminal and penultimate positions. Preferably 2 or more abasic nucleosides are consecutive, for example all abasic nucleosides may be consecutive. For example, the terminal 1 or terminal 2 or terminal 3 or terminal 4 nucelotides may be abasic nucleosides. An abasic nucleoside may also be linked to an adjacent nucleoside through a 5’-3’ phosphodiester linkage or reversed linkage unless there is only 1 abasic nucleoside at the terminus, in which case it will have a reversed linkage to the adjacent nucleoside. A reversed linkage (which may also be referred to as an inverted linkage, which is also seen in the art), comprises either a 5’-5’, a 3-’3’, a 3’-2’ or a 2’-3’ phosphodiester linkage between the adjacent sugar moieties of the nucleosides. Abasic nucleosides which are not terminal will have 2 phosphodiester bonds, one with each adjacent nucleoside, and these may be a reversed linkage or may be a 5’-3 phosphodiester bond or may be one of each. A preferred embodiment comprises 2 abasic nucleosides at the terminal and penultimate positions of the second strand, and wherein the reversed internucleoside linkage is located between the penultimate (abasic) nucleoside and the antepenultimate nucleoside. Preferably there are 2 abasic nucleosides at the terminal and penultimate positions of the second strand and the penultimate nucleoside is linked to the antepenultimate nucleoside through a reversed internucleoside linkage and is linked to the terminal nucleoside through a 5’-3’ or 3’-5’ phosphodiester linkage (reading in the direction of the terminus of the molecule). Preferably a nucleic acid according to the present invention comprises one or more abasic nucleosides, optionally wherein the one or more abasic nucleosides are in a terminal region of the second strand, and/or wherein at least one abasic nucleoside is linked to an adjacent basic nucleoside through a reversed internucleoside linkage. Different preferred features are as follows: The reversed internucleoside linkage is a 3’-3’ reversed linkage. The reversed internucleoside linkage is at a terminal region which is distal to the 5’ terminal phosphate of the second strand. The reversed internucleoside linkage is a 5’-5’ reversed linkage. The reversed internucleoside linkage is at a terminal region which is distal to the 3’ terminal hydroxide of the second strand. In certain embodiments, the second strand comprises 2 consecutive abasic nucleosides in the 5’ terminal region of the second strand, wherein one such abasic nucleoside is a terminal nucleoside at the 5’ terminal region of the second strand and the other abasic nucleoside is a penultimate nucleoside at the 5’ terminal region of the second strand, wherein: (a) said penultimate abasic nucleoside is connected to an adjacent first basic nucleoside in an adjacent 5’ near terminal region through a reversed internucleoside linkage; and (b) the reversed linkage is a 5-5’ reversed linkage; and (c) the linkage between the terminal and penultimate abasic nucleosides is 3’5’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides. More typically, (i) the first strand and the second strand each has a length of 23 nucleosides; (ii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in said 5’ near terminal region of the second strand, wherein a first phosphorothioate internucleoside linkage is present between said adjacent first basic nucleoside of (a) and an adjacent second basic nucleoside in said 5’ near terminal region of the second strand, and a second phosphorothioate internucleoside linkage is present between said adjacent second basic nucleoside and an adjacent third basic nucleoside in said 5’ near terminal region of the second strand; (iii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in both 5’ and 3’ terminal regions of the first strand, whereby a terminal nucleoside respectively at each of the 5’ and 3’ terminal regions of said first strand is each attached to a respective 5’ and 3’ adjacent penultimate nucleoside by a phosphorothioate internucleoside linkage, and each first 5’ and 3’ penultimate nucleoside is attached to a respective 5’ and 3’ adjacent antepenultimate nucleoside by a phosphorothioate internucleoside linkage; and (iv) the second strand of the nucleic acid is conjugated directly or indirectly to one or more ligand moieties at the 3’ terminal region of the second strand. Alternatively the second strand comprises 2 consecutive abasic nucleosides preferably in an overhang in the 3’ terminal region of the second strand, wherein one such abasic nucleoside is a terminal nucleoside at the 3’ terminal region of the second strand and the other abasic nucleoside is a penultimate nucleoside at the 3’ terminal region of the second strand, wherein: (a) said penultimate abasic nucleoside is connected to an adjacent first basic nucleoside in an adjacent 3’ near terminal region through a reversed internucleoside linkage; and (b) the reversed linkage is a 3-3’ reversed linkage; and (c) the linkage between the terminal and penultimate abasic nucleosides is 5’-3’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides. More typically, (i) the first strand and the second strand each has a length of 23 nucleosides; (ii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in said 3’ near terminal region of the second strand, wherein a first phosphorothioate internucleoside linkage is present between said adjacent first basic nucleoside of (a) and an adjacent second basic nucleoside in said 3’ near terminal region of the second strand, and a second phosphorothioate internucleoside linkage is present between said adjacent second basic nucleoside and an adjacent third basic nucleoside in said 3’ near terminal region of the second strand; (iii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in both 5’ and 3’ terminal regions of the first strand, whereby a terminal nucleoside respectively at each of the 5’ and 3’ terminal regions of said first strand is each attached to a respective 5’ and 3’ adjacent penultimate nucleoside by a phosphorothioate internucleoside linkage, and each first 5’ and 3’ penultimate nucleoside is attached to a respective 5’ and 3’ adjacent antepenultimate nucleoside by a phosphorothioate internucleoside linkage; and (iv) the second strand of the nucleic acid is conjugated directly or indirectly to one or more ligand moieties at the 5’ terminal region of the second strand. Examples of the structures are as follows (where the specific RNA nucleosides shown are not limiting and could be any RNA nucleoside): A A 3’-3’ reversed bond (and also showing the 5’-3 direction of the last phosphodiester bond between the two abasic molecules reading towards the terminus of the molecule)

B Illustrating a 5’-5’ reversed bond (and also showing the 3’-5’ direction of the last phosphodiester bond between the two abasic molecules reading towards the terminus of the molecule)

The abasic nucleoside or abasic nucleosides present in the nucleic acid are provided in the presence of a reversed internucleoside linkage or linkages, namely a 5’-5’ or a 3’-3’ reversed internucleoside linkage. A reversed linkage occurs as a result of a change of orientation of an adjacent nucleoside sugar, such that the sugar will have a 3’ – 5’ orientation as opposed to the conventional 5’ – 3’ orientation (with reference to the numbering of ring atoms on the nucleoside sugars). The abasic nucleoside or nucleosides as present in the nucleic acids of the invention preferably include such inverted nucleoside sugars. In the case of a terminal nucleoside having an inverted orientation, then this will result in an “inverted” end configuration for the overall nucleic acid. Whilst certain structures drawn and referenced herein are represented using conventional 5’ - 3’ direction (with reference to the numbering of ring atoms on the nucleoside sugars), it will be appreciated that the presence of a terminal nucleoside having a change of orientation and a proximal 3’-3’ reversed linkage, will result in a nucleic acid having an overall 5’- 5’ end structure (i.e. the conventional 3’ end nucleoside becomes a 5’ end nucleoside). Alternatively, it will be appreciated that the presence of a terminal nucleoside having a change of orientation and a proximal 5’-5’ reversed linkage will result in a nucleic acid with an overall 3’- 3’ end structure. The proximal 3’-3’ or 5’-5’ reversed linkage as herein described, may comprise the reversed linkage being directly adjacent / attached to a terminal nucleoside having an inverted orientation, such as a single terminal nucleoside having an inverted orientation. Alternatively, the proximal 3’-3’ or 5’-5’ reversed linkage as herein described, may comprise the reversed linkage being adjacent 2, or more than 2, nucleosides having an inverted orientation, such as 2, or more than 2, terminal region nucleosides having an inverted orientation, such as the terminal and penultimate nucleosides. In this way, the reversed linkage may be attached to a penultimate nucleoside having an inverted orientation. While a skilled addressee will appreciate that inverted orientations as described above can result in nucleic acid molecules having overall 3’ - 3’ or 5’- 5’ end structures as described herein, it will also be appreciated that with the presence of one or more additional reversed linkages and / or nucleosides having an inverted orientation, then the overall nucleic acid may have 3’ - 5’ end structures corresponding to the conventionally positioned 5’ / 3’ ends. In one aspect the nucleic acid may have a 3’-3’ reversed linkage, and the terminal sugar moiety may comprise a 5’ OH rather than a 5’ phosphate group at the 5’ position of that terminal sugar. A skilled person would therefore clearly understand that 5’-5’, 3’-3’ and 3’-5’ (reading in the direction of that terminus) end variants of the more conventional 5’-3’ structures (with reference to the numbering of ring atoms on the end nucleoside sugars) drawn herein are included in the scope of the disclosure, where a reversed linkage or linkages is / are present. In the situation of e.g. a reversed internucleoside linkage and / or one or more nucleosides having an inverted orientation creating an inverted end, and where the relative position of a linkage (e.g. to a linker) or the location of an internal feature (such as a modified nucleoside) is defined relative to the 5’ or 3’ end of the nucleic acid, then the 5’ or 3’ end is the conventional 5’ or 3’ end which would have existed had a reversed linkage not been in place, and wherein the conventional 5’ or 3’ end is determined by consideration of the directionality of the majority of the internal nucleoside linkages and / or nucleoside orientation within the nucleic acid. It is possible to tell from these internal bonds and / or nucleoside orientation which ends of the nucleic acid would constitute the conventional 5’ and 3’ ends (with reference to the numbering of ring atoms on the end nucleoside sugars) of the molecule absent the reversed linkage. For example, in the structure shown below there are abasic residues in the first 2 positions located at the “5’” end. Where the terminal nucleoside has an inverted orientation then the “5’” end indicated in the diagram below, which is the conventional 5’ end, can in fact comprise a 3’ OH in view of the inverted nucleoside at the terminal position. Nevertheless the majority of the molecule will comprise conventional internucleoside linkages that run from the 3’ OH of the sugar to the 5’ phosphate of the next sugar, when reading in the standard 5’ [PO4] to 3’ [OH] direction of a nucleic acid molecule (with reference to the numbering of ring atoms on the nucleoside sugars), which can be used to determine the conventional 5’ and 3’ ends that would be found absent the inverted end configuration. A 5’ A-A-Me-Me-Me-Me-Me-Me-F-Me-F-F-F-Me-Me-Me-Me-Me-Me-Me-Me-Me-Me 3’ The reversed bond is preferably located at the end of the nucleic acid e.g. RNA which is distal to a ligand moiety, such as a GalNAc containing portion, of the molecule. GalNAc-siRNA constructs with a 5’-GalNAc on the sense strand can have a reversed linkage on the opposite end of the sense strand. GalNAc-siRNA constructs with a 3’-GalNAc on the sense strand can have a reversed linkage on the opposite end of the sense strand. In some embodiments, the second (sense) strand of the nucleic acid according to the invention comprises 2 consecutive abasic nucleosides in the 5’ terminal region as shown in the following 5’ terminal motif

wherein: B represents a nucleoside base, T represent H, OH or a 2’ ribose modification, Z represents the remaining nucleosides of said second strand. In some embodiments, the second (sense) strand of the nucleic acid according to the invention comprises 2 consecutive abasic nucleosides in the 5’ terminal region as shown in the following 5’ terminal motif

wherein: B represents a nucleoside base, T represents H, OH or a 2’ ribose modification (preferably a 2’ ribose modification, more preferably a 2’Me or 2’F ribose modification), V represents O or S (preferably O), R represents H or C_1-4 alkyl (preferably H), Z represents the remaining nucleosides of said second strand, more preferably the following 5’ terminal motif

wherein: B represents a nucleoside base, T represents a 2’ ribose modification (preferably a 2’Me or 2’F ribose modification), Z represents the remaining nucleosides of said second strand. The reversed bond is preferably located at the end of the nucleic acid eg RNA which is distal to a ligand moiety, such as a GalNAc containing portion, of the molecule. GalNAc-siRNA constructs with a 5’-GalNAc on the sense strand can have a reversed linkage on the opposite end of the sense strand. GalNAc-siRNA constructs with a 3’-GalNAc on the sense strand can have a reversed linkage on the opposite end of the sense strand. In a preferred embodiment, the second (sense) strand of the nucleic acid according to the invention comprises 2 consecutive abasic nucleosides in the 5’ terminal region as shown in the following 5’ terminal motif

wherein: B represents a nucleoside base, T represent H, OH or a 2’ ribose modification (preferably a 2’ ribose modification, more preferably a 2’Me or 2’F ribose modification), V represent O or S (preferably O), R represent H or C_1-4 alkyl (preferably H), Z comprises 11 to 26 contiguous nucleosides, preferably 15 to 21 contiguous nucleosides, and more preferably 19 contiguous nucleosides, more preferably the following 5’ terminal motif

wherein: B represents a nucleoside base, T represents a 2’ ribose modification (preferably a 2’Me or 2’F ribose modification), Z comprises 19 contiguous nucleosides. NUCLEIC ACID LENGTHS In one aspect the i) the first strand of the nucleic acid has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 23 nucleosides; and / or ii) the second strand of the nucleic acid has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 21 nucleosides. Typically, the duplex region of the nucleic acid is between 17 and 30 nucleosides in length, more preferably is 19 or 21 nucleosides in length. Similarly, the region of complementarity between the first strand and the portion of RNA transcribed from the SLC25A5 gene is between 17 and 30 nucleosides in length. Generally, the duplex structure of the nucleic acid e.g. an iRNA is about 15 to 30 base pairs in length, e.g., 15-29, 15-28, 15-27, 15-26, 15-25, 15-24, 15-23, 15-22, 15-21, 15-20, 15-19, 15-18, 15-17, 18-30, 18-29, 18-28, 18-27, 18-26, 18-25, 18-24, 18-23, 18-22, 18-21, 18-20, 19-30, 19- 29, 19-28, 19-27, 19-26, 19-25, 19-24, 19- 23, 19-22, 19-21, 19-20, 20-30, 20-29, 20-28, 20-27, 20-26, 20-25, 20-24,20-23, 20-22, 20-21, 21-30, 21-29, 21-28, 21-27, 21-26, 21-25, 21-24, 21- 23, or 21-22 base pairs in length. Ranges and lengths intermediate to the above recited ranges and lengths are also contemplated to be part of the invention. Similarly, the region of complementarity of an antisense sequence to a target sequence and/or the region of complementarity of an antisense sequence to a sense sequence is about 15 to 30 nucleosides in length, e.g., 15-29, 15-28, 15-27, 15-26, 15-25, 15-24, 15-23, 15-22, 15-21, 15-20, 15-19, 15-18, 15-17, 18-30, 18-29, 18-28, 18-27, 18-26, 18-25, 18-24, 18-23, 18-22, 18-21, 18- 20, 19-30, 19-29, 19-28, 19-27, 19-26, 19-25, 19-24, 19-23, 19-22, 19-21, 19-20, 20-30, 20-29, 20-28, 20-27, 20-26, 20-25, 20- 24,20-23, 20-22, 20-21, 21-30, 21-29, 21-28, 21-27, 21-26, 21- 25, 21-24, 21-23, or 21-22 nucleosides in length. Ranges and lengths intermediate to the above recited ranges and lengths are also contemplated to be part of the invention. In certain preferred embodiments, the region of complementarity of an antisense sequence to a target sequence and/or the region of complementarity of an antisense sequence to a sense sequence is at least 17 nucleosides in length. For example, the region of complementarity between the antisense strand and the target is 19 to 21 nucleosides in length, for example, the region of complementarity is 21 nucleosides in length. In preferred embodiments, each strand is no more than 30 nucleosides in length. In certain preferred embodiments, the duplex structure of the nucleic acid e.g. an siRNA is 19 or 21 base pairs in length. In particularly preferred embodiment, the duplex may have one of the following structures: e.g., ETX-M00001351 – ETX-M00001626

or A nucleic acid e.g. a dsRNA as described herein can further include one or more single-stranded nucleoside overhangs e.g., 1-4, 2-4, 1-3, 2-3, 1, 2, 3, or 4 nucleosides. A nucleoside overhang can comprise or consist of a nucleoside/nucleoside analog, including a deoxynucleoside/nucleoside. The overhang(s) can be on the sense strand, the antisense strand, or any combination thereof. Furthermore, the nucleoside(s) of an overhang can be present on the 5'- end, 3'- end, or both ends of an antisense or sense strand of a nucleic acid e.g. a dsRNA. In certain preferred embodiments, at least one strand comprises a 3' overhang of at least 1 nucleoside, e.g. , at least one strand comprises a 3' overhang of at least 2 nucleosides. The overhang is suitably on the antisense/ guide strand and/or the sense / passenger strand. NUCLEIC ACID MODIFICATIONS In certain embodiments, the nucleic acid e.g. an RNA of the invention e.g., a dsiRNA, does not comprise further modifications, e.g., chemical modifications or conjugations known in the art and described herein. In other preferred embodiments, the nucleic acid e.g. RNA of the invention, e.g., a dsiRNA, is further chemically modified to enhance stability or other beneficial characteristics. In certain embodiments of the invention, substantially all of the nucleosides are modified. The nucleic acids featured in the invention can be synthesized or modified by methods well established in the art, such as those described in "Current protocols in nucleic acid chemistry," Beaucage, S.L. et al. (Edrs.), John Wiley & Sons, Inc., New York, NY, USA, which is hereby incorporated herein by reference. Modifications include, for example, end modifications, e.g., 5'-end modifications (phosphorylation, conjugation, inverted linkages) or 3 '-end modifications (conjugation, DNA nucleosides within an RNA, or RNA nucleosides within a DNA, inverted linkages, etc.); base modifications, e.g., replacement with stabilizing bases, destabilizing bases, or bases that base pair with an expanded repertoire of partners, conjugated bases; sugar modifications (e.g. , at the 2'-position or 4'- position) or replacement of the sugar; or backbone modifications, including modification or replacement of the phosphodiester linkages. Specific examples of nucleic acids such as siRNA compounds useful in the embodiments described herein include, but are not limited to RNAs containing modified backbones or no natural internucleoside linkages. Nucleic acids such as RNAs having modified backbones include, among others, 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 nucleic acids e.g. RNAs that do not have a phosphorus atom in their internucleoside backbone can also be considered to be oligonucleosides. In some embodiments, a modified nucleic acid e.g. an siRNA will have a phosphorus atom in its internucleoside backbone. Modified nucleic acid e.g. RNA 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 5'-3' or 5'-2'. Various salts, mixed salts and free acid forms are also included. Modified nucleic acids e.g. RNAs can also contain one or more substituted sugar moieties. The nucleic acids e.g. siRNAs, e.g., dsiRNAs, featured herein can include 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 can be substituted or unsubstituted. 2’ O- methyl and 2’-F are preferred modifications. In certain preferred embodiments, the nucleic acid comprises at least one modified nucleoside. The nucleic acid of the invention may comprise one or more modified nucleosides on the first strand and/or the second strand. In some embodiments, substantially all of the nucleosides of the sense strand and all of the nucleosides of the antisense strand comprise a modification. In some embodiments, all of the nucleosides of the sense strand and substantially all of the nucleosides of the antisense strand comprise a modification. In some embodiments, all of the nucleosides of the sense strand and all of the nucleosides of the antisense strand comprise a modification. In one embodiment, at least one of the modified nucleosides is selected from the group consisting of a deoxy- nucleoside, a 3 '-terminal deoxy-thymine (dT) nucleoside, a 2'-O-methyl modified nucleoside (also called herein 2’-Me, where Me is a methoxy) , a 2'-fluoro modified nucleoside, a 2'-deoxy- modified nucleoside, a locked nucleoside, an unlocked nucleoside, a conformationally restricted nucleoside, a constrained ethyl nucleoside, an abasic nucleoside, a 2' -amino- modified nucleoside, a 2'-O-allyl- modified nucleoside, 2' -C-alkyl- modified nucleoside, 2'-hydroxly-modified nucleoside, a 2'- methoxyethyl modified nucleoside, a 2'-O- alkyl-modified nucleoside, a morpholino nucleoside, a phosphoramidate, a non-natural base comprising nucleoside, a tetrahydropyran modified nucleoside, a 1 ,5-anhydrohexitol modified nucleoside, a cyclohexenyl modified nucleoside, a nucleoside comprising a phosphorothioate group, a nucleoside comprising a methylphosphonate group, a nucleoside comprising a 5 '- phosphate, and a nucleoside comprising a 5 '-phosphate mimic. In another embodiment, the modified nucleosides comprise a short sequence of 3 '-terminal deoxy-thymine nucleosides (dT). Modifications on the nucleosides may preferably be selected from the group including, but not limited to, LNA, HNA, CeNA, 2 -methoxyethyl, 2'-O-alkyl, 2-O-allyl, 2'-C-allyl, 2'-fluoro, 2'- deoxy, 2'-hydroxyl, and combinations thereof. In another embodiment, the modifications on the nucleosides are 2 -O-methyl (“2-Me”) or 2'-fluoro modifications. One preferred modification is a modification at the 2’-OH group of the ribose sugar, optionally selected from 2'-Me or 2’-F modifications. In certain embodiments, the nucleic acid e.g. RNAi agent further comprises at least one phosphorothioate or methylphosphonate internucleoside linkage. For example the phosphorothioate or methylphosphonate internucleoside linkage can be at the 3 '-terminus or in the terminal region of one strand, i.e. , the sense strand or the antisense strand; or at the ends of both strands, the sense strand and the antisense strand. In certain embodiments, the phosphorothioate or methylphosphonate internucleoside linkage is at the 5 'terminus or in the terminal region of one strand, i.e. , the sense strand or the antisense strand; or at the ends of both strands, the sense strand and the antisense strand. In certain embodiments, a phosphorothioate or a methylphosphonate internucleoside linkage is at both the 5'- and 3 '-terminus or in the terminal region of one strand, i.e. , the sense strand or the antisense strand; or at the ends of both strands, the sense strand and the antisense strand. Any nucleic acid may comprise one or more phosphorothioate (PS) modifications within the nucleic acid, such as at least two PS internucleoside bonds at the ends of a strand. At least one of the oligoribonucleoside strands preferably comprises at least two consecutive phosphorothioate modifications in the last 3 nucleosides of the oligonucleoside. The invention therefore also relates to: A nucleic acid disclosed herein which comprises phosphorothioate internucleoside linkages respectively between at least two or three consecutive positions, such as in a 5’ and/or 3’ terminal region and/or near terminal region of the second strand, whereby said near terminal region is preferably adjacent said terminal region wherein said one or more abasic nucleosides of said second strand is / are located. A nucleic acid disclosed herein which comprises phosphorothioate internucleoside linkages respectively between at least two or three consecutive positions in a 5’ and / or 3’ terminal region of the first strand, whereby preferably the terminal position at the 5’ and / or 3’ terminal region of said first strand is attached to its adjacent position by a phosphorothioate internucleoside linkage. The nucleic acid strand may be an RNA comprising a phosphorothioate internucleoside linkage between the three nucleosides contiguous with 2 terminally located abasic nucleosides. A preferred nucleic acid is a double stranded RNA comprising 2 adjacent abasic nucleosides at the 5’ terminus of the second strand and a ligand moiety comprising one or more GalNAc ligand moieties at the opposite 3’ end of the second strand. Further preferred, the same nucleic acid may also comprise a phosphorothioate bond between nucelotides at positions 3-4 and 4-5 of the second strand, reading from the position 1 of the second strand. Position 1 of the first or the second strand is the nucleoside which is the closest to the end of the nucleic acid (ignoring any abasic nucleosides) and that is joined to an adjacent nucleoside (at Position 2) via a 3’ to 5’ internal bond, with reference to the bonds between the sugar moieties of the backbone, and reading in a direction away from that end of the molecule. It can therefore be seen that “position 1 of the sense strand” is the 5’ most nucleoside (not including abasic nucleosides) at the conventional 5’ end of the sense strand. Typically, the nucleoside at this position 1 of the sense strand will be equivalent to the 5’ nucleoside of the selected target nucleic acid sequence, and more generally the sense strand will have equivalent nucleosides to those of the target nucleic acid sequence starting from this position 1 of the sense strand, whilst also allowing for acceptable mismatches between the sequences. As used herein, “position 1 of the antisense strand” is the 5’ most nucleoside (not including abasic nucleosides) at the conventional 5’ end of the antisense strand. As hereinbefore described, there will be a region of complementarity between the sense and antisense strands, and in this way the antisense strand will also have a region of complementarity to the target nucleic acid sequence as referred to above. Preferred modifications that can be used with sequences according to the present invention can be as follows: Modification 1: First strand modification: NmsNfsNmNfNmNfNmNfNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNfNfNfNfNfNmNmNmNmNmNmNmNfNmNm (5’ to 3’) Modification 2: First strand modification: NmsNfsNmNfNmNfNmNfNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNfNfNmNfNfNfNfNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 3: First strand modification: NmsNfsNmNfNmNfNmNfNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNfNmNfNfNfNfNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 4: First strand modification: NmsNfsNmNfNmNfNmNmNmNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNfNmNfNfNfNfNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 5: First strand modification: NmsNfsNmNmNmNfNmNmNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 6: First strand modification: NmsNfsNmNmNmNfNmNmNmNmNmNmNmNfNmNfNmNfNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 7: First strand modification: NmsNfsNmNmNmNyNmNmNmNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 8: First strand modification: NmsNfsNmNmNmNyNmNfNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 9: First strand modification: NmsNfsNmNmNmNfNmNmNmNmNmNmNmNfNmNfNmNmNmNfNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 10: First strand modification: NmsNfsNmNfNmNfNmNmNmNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 11: First strand modification: NmsNfsNmNfNmNfNmNfNfNmNmNmNmNfNmNfNmNmNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 12: First strand modification: NmsNfsNmNmNmNfNmNfNfNmNmNmNmNfNmNfNmNfNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) Modification 13: First strand modification: NmsNfsNmNmNmNfNmNfNfNmNmNmNmNfNmNfNmNmNmNfNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) wherein in each of the above modifications: ia represents an inverted abasic nucleoside; Nm represents a 2’Me ribose modified nucleoside; Nf represents a 2’F ribose modified nucleoside; Ny represents a nucleoside with a thermally destabilizing modification, preferably wherein the destabilizing modification is selected from a modified unlocked nucleic acid (UNA) and a glycol nucleic acid (GNA), more preferably a glycol nucleic acid, most preferably an (S)-glycol nucleic acid; s represents a phosphorothioate internucleoside bond. A particularly preferred modification that can be used with sequences according to the present invention can be: Modification 6: First strand modification: NmsNfsNmNmNmNfNmNmNmNmNmNmNmNfNmNfNmNfNmNmNmsNmsNm (5’ to 3’) Second strand modification: iaiaNmsNmsNmNmNmNmNmNmNfNfNfNmNmNmNmNmNmNmNmNmNm (5’ to 3’) wherein in each of the above modifications: ia represents an inverted abasic nucleoside; Nm represents a 2’Me ribose modified nucleoside; and s represents a phosphorothioate internucleoside bond. CONJUGATION OF NUCLEIC ACID TO LIGAND Another modification of a nucleic acid e.g. RNA e.g. an siRNA of the invention involves linking the nucleic acid e.g. the siRNA to one or more ligand moieties e.g. to enhance the activity, cellular distribution, or cellular uptake of the nucleic acid e.g. siRNA e.g., into a cell. In certain embodiments, the inhibitor according to the invention is conjugated to a ligand moiety that enables and/or facilitates targeting of hepatocytes. In certain embodiments, targeting of hepatocytes is achieved using N-acetylgalactosamine (GalNAc) conjugates as described in more detail herein below. That is, in certain embodiments, the inhibitor according to the invention is an siRNA-GalNAc conjugate. In some embodiments, the ligand moiety described can be attached to a nucleic acid e.g. an siRNA oligonucleoside, via a linker that can be cleavable or non-cleavable. The term "linker" or "linking group" means an organic moiety that connects two parts of a compound, e.g., covalently attaches two parts of a compound. The ligand can be attached to the 3' or 5’ end of the sense strand. The ligand is preferably conjugated to 3’ end of the sense strand of the nucleic acid e.g. an siRNA agent. The invention therefore relates in a further aspect to a conjugate for inhibiting expression of a target e.g. a target gene, in a cell, said conjugate comprising a nucleic acid portion and one or more ligand moieties, said nucleic acid portion comprising a nucleic acid as disclosed herein. In one aspect the second strand of the nucleic acid is conjugated directly or indirectly (e.g. via a linker) to the one or more ligand moiety(s), wherein said ligand moiety is typically present at a terminal region of the second strand, preferably at the 3’ terminal region thereof. In certain embodiments, the ligand moiety comprises a GalNAc or GalNAc derivative attached to the nucleic acid e.g. dsiRNA through a linker. Therefore, the invention relates to a conjugate wherein the ligand moiety comprises i) one or more GalNAc ligands; and/or ii) one or more GalNAc ligand derivatives; and/or iii) one or more GalNAc ligands conjugated to said nucleic acid through a linker. Said GalNAc ligand may be conjugated directly or indirectly to the 5’ or 3’ terminal region of the second strand of the nucleic acid, preferably at the 3’ terminal region thereof. GalNAc ligands are well known in the art and described in, inter alia, EP3775207A1. In some embodiments, the ligand moiety comprises one or more ligands. In some embodiments, the ligand moiety comprises one or more carbohydrate ligands. In some embodiments, the one or more carbohydrates can be a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide and / or polysaccharide. In some embodiments, the one or more carbohydrates comprise one or more galactose moieties, one or more lactose moieties, one or more N-AcetylGalactosamine moieties, and / or one or more mannose moieties. In some embodiments, the one or more carbohydrates comprise one or more N-Acetyl- Galactosamine moieties. In some embodiments, the compounds as described anywhere herein comprise two or three N- AcetylGalactosamine moieties. In some embodiments, the one or more ligands are attached in a linear configuration, or in a branched configuration, for example each configuration being respectively attached to a branch point in an overall linker. Exemplary linear configurations and Exemplary branched configurations are shown in Figures 1a and 1b: In Fig 1a, (linear), (a) and / or (b) can typically represent connecting bonds or groups, such as phosphate or phosphorothioate groups. In Fig 1b, (branched), in some embodiments, the one or more ligands are attached as a biantennary or triantennary branched configuration. Typically, a triantennary branched configuration can be preferred, such as an N-AcetylGalactosamine triantennary branched configuration. Linker Exemplary compounds of the invention comprise a ‘linker moiety’, such as that as depicted in Formula (I), that is part of an overall ‘linker’. Formula I

wherein: R₁ at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1-3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; m is an integer of from 1 to 6; n is an integer of from 1 to 10; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety. As will be further understood in the art, exemplary compounds of the invention comprise an overall linker that is located between the oligonucleoside moiety and the ligand moiety of these compounds. The overall linker, thereby ‘links’ the oligonucleoside moiety and the ligand moiety to each other. The overall linker is often notionally envisaged as comprising one or more linker building blocks. For example, there is a linker portion that is depicted as the ‘linker moiety’ as represented in Formula (I) positioned adjacent the ligand moiety and attaching the ligand moiety, typically via a branch point, directly or indirectly to the oligonucleoside moiety. The linker moiety as depicted in Formula (I) can also often be referred to as the ‘ligand arm or arms’ of the overall linker. There can also, but not always, be a further linker portion between the oligonucleoside moiety and the branch point, that is often referred to as the ‘tether moiety’ of the overall linker, ‘tethering’ the oligonucleoside moiety to the remainder of the conjugated compound. Such ‘ligand arms’ and / or ‘linker moieties’ and / or ‘tether moieties’ can be envisaged by reference to the linear and / or branched configurations as set out above. As can be seen from the claims, and the reminder of the patent specification, the scope of the present invention extends to linear or branched configurations, and with no limitation as to the number of individual ligands that might be present. Furthermore, the addressee will also be aware that there are many structures that could be used as the linker moiety, based on the state of the art and the expertise of an oligonucleoside chemist. The remainder of the overall linker (other than the linker moiety) as set out in the claims, and the remainder of the patent specification, is shown by its chemical constituents in Formula (I), which the inventors consider to be particularly unique to the current invention. In more general terms, however, these chemical constituents could be described as a ‘tether moiety’ as hereinbefore described, wherein the ‘tether moiety’ is that portion of the overall linker which comprises the group of atoms between Z, namely the oligonucleoside moiety, and the linker moiety as depicted in Formula (I). Tether moiety of Formula I In relation to Formula (I), the ‘tether moiety’ comprises the group of atoms between Z, namely the oligonucleoside moiety, and the linker moiety. In some embodiments, R1 is hydrogen at each occurrence. In some embodiments, R1 is methyl. In some embodiments, R1 is ethyl. In some embodiments, R₂ is hydroxy. In some embodiments, R₂ is halo. In some embodiments, R₂ is fluoro. In some embodiments, R₂ is chloro. In some embodiments, R₂ is bromo. In some embodiments, R2 is iodo. In some embodiments, R2 is nitro. In some embodiments, X₁ is methylene. In some embodiments, X₁ is oxygen. In some embodiments, X₁ is sulfur. In some embodiments, X2 is methylene. In some embodiments, X2 is oxygen. In some embodiments, X2 is sulfur. In some embodiments, m = 3. In some embodiments, n = 6. In some embodiments, X1 is oxygen and X2 is methylene. In some embodiments, both X1 and X2 are methylene. In some embodiments, q = 1, r = 2, s = 1, t = 1, v = 1. In some embodiments, q = 1, r = 3, s = 1, t = 1, v = 1. In some embodiments, R₁ is hydrogen at each occurrence, n = 6, m = 3, R₂ is fluoro, X₂ is methylene, v = 1, t = 1, s = 1, X₁ is methylene, q = 1 and r = 2. Thus, in some embodiments, exemplary compounds of the invention comprise the following structure:

Formula (IV) In some embodiments, R1 is hydrogen at each occurrence, n = 6, m = 3, R2 is fluoro, X2 is methylene, v = 1, t = 1, s = 1, X1 is oxygen, q = 1 and r = 2. Thus, in some embodiments, exemplary compounds of the invention comprise the following structure: Formula (II) Alternative tether moieties During the synthesis of compounds of the present invention, alternative tether moiety structures may arise. In some embodiments, alternative tether moieties have a change of one or more atoms in the tether moiety of the overall linker compared to tether moieties described anywhere herein. In some embodiments, the alternative tether moiety is a compound of Formula (I) as described anywhere herein, wherein R2 is hydroxy. In some embodiments, R₁ is hydrogen at each occurrence, n = 6, m = 3, R₂ is hydroxy, X₂ is methylene, v = 1, t = 1, s = 1, X1 is methylene, q = 1 and r = 2. Thus, in some embodiments, compounds of the invention comprise the following structure:

Formula (V) In some embodiments, R₁ is hydrogen at each occurrence, n = 6, m = 3, R₂ is hydroxy, X₂ is methylene, v = 1, t = 1, s = 1, X1 is oxygen, q = 1 and r = 2. Thus, in some embodiments, compounds of the invention comprise the following structure:

Formula (III) Linker moiety In relation to Formula (I), the ‘linker moiety’ as depicted in Formula (I) comprises the group of atoms located between the tether moiety as described anywhere herein, and the ligand moiety as described anywhere herein. In some embodiments:

as depicted in Formula (I) as described anywhere herein is any of Formulae (VIa), (VIb) or (VIc), preferably Formula (VIa):

Formula (VIa) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and b is an integer of 2 to 5; or

Formula (VIb) wherein: AI is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and c and d are independently integers of 1 to 6; or

Formula (VIc) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and e is an integer of 2 to 10. In some embodiments, the moiety:

as depicted in Formula (I) is Formula (VIa):

Formula (VIa) wherein: AI is hydrogen, or a suitable hydroxy protecting group; a is 3; and b is an integer of 3. In some embodiments, the moiety:

as depicted in Formula (I) as described anywhere herein is Formula (VII):

Formula (VII) wherein: AI is hydrogen; a is an integer of 2 or 3, preferably 3. Other exemplary compounds of the invention comprise a ‘linker moiety’, as depicted in Formula (I*), that is part of an overall ‘linker’.

Formula I* Where: r and s are independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety. As will be further understood in the art, exemplary compounds of the invention comprise an overall linker that is located between the oligonucleoside moiety and the ligand moiety of these compounds. The overall linker, thereby ‘links’ the oligonucleoside moiety and the ligand moiety to each other. The overall linker is often notionally envisaged as comprising one or more linker building blocks. For example, there is a linker portion that is depicted as the ‘linker moiety’ as represented in Formula (I*) positioned adjacent the ligand moiety and attaching the ligand moiety, typically via a branch point, directly or indirectly to the oligonucleoside moiety. The linker moiety as depicted in Formula (I*) can also often be referred to as the ‘ligand arm or arms’ of the overall linker. There can also, but not always, be a further linker portion between the oligonucleoside moiety and the branch point, that is often referred to as the ‘tether moiety’ of the overall linker, ‘tethering’ the oligonucleoside moiety to the remainder of the conjugated compound. Such ‘ligand arms’ and / or ‘linker moieties’ and / or ‘tether moieties’ can be envisaged by reference to the linear and / or branched configurations as set out above. As can be seen from the claims, and the reminder of the patent specification, the scope of the present invention extends to linear or branched configurations, and with no limitation as to the number of individual ligands that might be present. Furthermore, the addressee will also be aware that there are many structures that could be used as the linker moiety, based on the state of the art and the expertise of an oligonucleoside chemist. The remainder of the overall linker (other than the linker moiety) as set out in the claims, and the remainder of the patent specification, is shown by its chemical constituents in Formula (I), which the inventors consider to be particularly unique to the current invention. In more general terms, however, these chemical constituents could be described as a ‘tether moiety’ as hereinbefore described, wherein the ‘tether moiety’ is that portion of the overall linker which comprises the group of atoms between Z, namely the oligonucleoside moiety, and the linker moiety as depicted in Formula (I). Tether moiety In relation to Formula (I*), the ‘tether moiety’ comprises the group of atoms between Z, namely the oligonucleoside moiety, and the linker moiety. In some embodiments, s is an integer selected from 4 to 12. In some embodiments, s is 6. In some embodiments, r is an integer selected from 4 to 14. In some embodiments, r is 6. In some embodiments, r is 12. In some embodiments, r is 12 and s is 6. Thus, in some embodiments, exemplary compounds of the invention comprise the following structure:

Formula (II*) In some embodiments, r is 6 and s is 6. Thus, in some embodiments, exemplary compounds of the invention comprise the following structure:

Formula (III*) Linker moiety In relation to Formula (I*), the ‘linker moiety’ as depicted in Formula (I) comprises the group of atoms located between the tether moiety as described anywhere herein, and the ligand moiety as described anywhere herein. In some embodiments, the moiety:

as depicted in Formula (I*) as described anywhere herein is any of Formulae (IV*), (V*) or (VI*), preferably Formula (IV*):

Formula (IV*) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and b is an integer of 2 to 5; or

Formula (V*) wherein: AI is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and c and d are independently integers of 1 to 6; or

Formula (VI*) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and e is an integer of 2 to 10. In some embodiments, the moiety:

as depicted in Formula (I) is Formula (VIa*):

Formula (VIa*) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is 3; and b is an integer of 3. In some embodiments, the moiety: as depicted in Formula (I) as described anywhere herein is Formula (VII*):

Formula (VII*) wherein: A_I is hydrogen; a is an integer of 2 or 3. In some embodiments, a = 2. In some embodiments, a = 3. In some embodiments, b = 3. In some embodiments, the GalNAc ligand is comprised in any one of the linkers shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" may be any nucleic acid disclosed herein. Accordingly, the "oligonucleotide" may comprise other bonds than a phosphodiester bond, such as one or more phosphorothioate bonds. Preferably, the nucleic acid according to the invention is a double stranded oligonucleoside as defined herein and the linker is conjugated to the second strand, more preferably to the 3' terminal region of the second strand, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" may be any nucleic acid disclosed herein. Accordingly, the "oligonucleotide" may comprise other bonds than a phosphodiester bond, such as one or more phosphorothioate bonds. Preferably, the nucleic acid according to the invention is a double stranded oligonucleoside as defined herein and the linker is conjugated to the second strand, more preferably to the 3' terminal region of the second strand, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 6 (Formula XI), wherein the "oligonucleotide" may be any nucleic acid disclosed herein. Accordingly, the "oligonucleotide" may comprise other bonds than a phosphodiester bond, such as one or more phosphorothioate bonds. Preferably, the nucleic acid according to the invention is a double stranded oligonucleoside as defined herein and the linker is conjugated to the second strand, more preferably to the 3' terminal region of the second strand, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in any one of the linkers shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:553 to SEQ ID NO:828, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:553 to SEQ ID NO:828, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:553 to SEQ ID NO:828, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:553 to SEQ ID NO:828, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:553 to SEQ ID NO:828, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one SEQ ID NO:553 to SEQ ID NO:828, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in any one of the linkers shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 or SEQ ID NO:772, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 5 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified or unmodified second strand comprising or consisting of any one of SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in any one of the linkers shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in any one of the linkers shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, preferably wherein the linker is conjugated to the 3' terminal region of the second strand, i.e., to the 3' terminal region of any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, via a phosphodiester bond. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figures 2 to 5 or Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, wherein the second strand has the following structure

wherein: T represents a 2’Me ribose modification, B represents the nucleoside bases of the first two basic nucleosides in the 5' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, and Z represents the remaining 19 contiguous basic nucleosides of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, respectively. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 6 (Formula XI), wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, wherein the second strand has the following structure

wherein: T represents a 2’Me ribose modification, B represents the nucleoside bases of the first two basic nucleosides in the 5' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, and Z represents the remaining 19 contiguous basic nucleosides of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, respectively. In some embodiments, the GalNAc ligand is comprised in the linker shown in Figure 4, wherein the "oligonucleotide" represents a nucleic acid according to the invention, wherein the nucleic acid according to the invention comprises a modified second strand comprising or consisting of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, wherein the second strand has the following structure

wherein: T represents a 2’Me ribose modification, B represents the nucleoside bases of the first two basic nucleosides in the 5' terminal region of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, and Z represents the remaining 19 contiguous basic nucleosides of any one of SEQ ID NO:1105 to SEQ ID NO:1380, preferably any one of SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324, respectively. VECTOR AND CELL In one aspect, the invention provides a cell containing a nucleic acid, such as inhibitory RNA [RNAi] as described herein. In one aspect, the invention provides a cell comprising a vector as described herein. In one aspect the invention provides a vector comprising an oligonucleotide inhibitor, e.g.an iRNA e.g. siRNA. PHARMACEUTICALLY ACCEPTABLE COMPOSITIONS In one aspect, the invention provides a pharmaceutical composition for inhibiting expression of a target gene, the composition comprising an inhibitor such as an oligomer such as a nucleic acid as disclosed herein. The pharmaceutically acceptable composition may comprise an excipient and or carrier. Some examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen- free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffered solutions; (21) polyesters, polycarbonates and/or poly anhydrides; (22) bulking agents, such as polypeptides and amino acids (23) serum component, such as serum albumin, HDL and LDL; and (22) other non-toxic compatible substances employed in pharmaceutical formulations. 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). Pharmaceutically acceptable organic or inorganic excipients suitable for non-parenteral administration which do not deleteriously react with nucleic acids can also be used to formulate the compositions of the present invention. Suitable pharmaceutically acceptable excipients 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. Formulations for topical administration of nucleic acids can 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 can 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. In one embodiment, the nucleic acid or composition is administered in an unbuffered solution. In certain embodiments, the unbuffered solution is saline or water. In other embodiments, the nucleic acid e.g. RNAi agent is administered in a buffered solution. In such embodiments, the buffer solution can comprise acetate, citrate, prolamine, carbonate, or phosphate, or any combination thereof. For example, the buffer solution can be phosphate buffered saline (PBS). DOSAGES The pharmaceutical compositions of the invention may be administered in dosages sufficient to inhibit expression of a gene or modify the expression or function of a target. In general, where the composition comprising a nucleic acid, a suitable dose of a nucleic acid e.g. an siRNA of the invention will be in the range of about 0.001 to about 200.0 milligrams per kilogram body weight of the recipient per day, generally in the range of about 1 to 50 mg per kilogram body weight per day. Typically, a suitable dose of a nucleic acid e.g. an siRNA of the invention will be in the range of about 0.1 mg/kg to about 5.0 mg/kg, e.g., about 0.3 mg/kg and about 3.0 mg/kg. A repeat-dose regimen may include administration of a therapeutic amount of a nucleic acid e.g. siRNA on a regular basis, such as every other day or once a year. In certain embodiments, the nucleic acid e.g. siRNA is administered about once per month to about once per quarter (i.e., about once every three months). In various embodiments, the nucleic acid e.g. siRNA agent is administered at a dose of about 0.01 mg/kg to about 10 mg/kg or about 0.5 mg/kg to about 50 mg/kg. In some embodiments, the nucleic acid e.g. siRNA agent is administered at a dose of about 10 mg/kg to about 30 mg/kg. In certain embodiments, the nucleic acid e.g. siRNA agent is administered at a dose selected from about 0.5 mg/kg 1 mg/kg, 1.5 mg/kg, 3 mg/kg, 5 mg/kg, 10 mg/kg, and 30 mg/kg. In certain embodiments, the nucleic acid e.g. siRNA agent is administered about once per week, once per month, once every other two months, or once a quarter (i.e., once every three months) at a dose of about 0.1 mg/kg to about 5.0 mg/kg. In certain embodiments, the nucleic acid e.g. siRNA agent is administered to the subject once a week. In certain embodiments, the nucleic acid e.g. siRNA agent is administered to the subject once a month. In certain embodiments, the nucleic acid e.g. siRNA agent is administered once per quarter (i.e., every three months). After an initial treatment regimen, the treatments can be administered on a less frequent basis. For example, after administration weekly or biweekly for three months, administration can be repeated once per month, for six months, or a year; or longer. The pharmaceutical composition can be administered once daily, or administered as two, three, or more sub-doses at appropriate intervals throughout the day or even using continuous infusion or delivery through a controlled release formulation. In that case, the nucleic acid e.g. siRNA contained in each sub-dose must be correspondingly smaller in order to achieve the total daily dosage. The dosage unit can also be compounded for delivery over several days, e.g., using a conventional sustained release formulation which provides sustained release of the nucleic acid e.g. siRNA over a several day period. Sustained release formulations are well known in the art and are particularly useful for delivery of agents at a particular site, such as could be used with the agents of the present invention. In this embodiment, the dosage unit contains a corresponding multiple of the daily dose. In other embodiments, a single dose of the pharmaceutical compositions can be long lasting, such that subsequent doses are administered at not more than 3, 4, or 5 day intervals, or at not more than 1, 2, 3, or 4 week intervals. In some embodiments of the invention, a single dose of the pharmaceutical compositions of the invention is administered once per week. In other embodiments of the invention, a single dose of the pharmaceutical compositions of the invention is administered bimonthly. In certain embodiments, the siRNA is administered about once per month to about once per quarter (i.e., about once every three months), or even every 6 months or 12 months. Estimates of effective dosages and in vivo half-lives for the individual nucleic acid e.g. siRNAs encompassed by the invention can be made using conventional methodologies or on the basis of in vivo testing using an appropriate animal model, as known in the art. The pharmaceutical compositions of the present invention can be administered in a number of ways depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration can be topical (e.g., by a transdermal patch), 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; subdermal, e.g., via an implanted device; or intracranial, e.g., by intraparenchymal, intrathecal or intraventricular administration. In certain preferred embodiments, the compositions are administered by intravenous infusion or injection. In certain embodiments, the compositions are administered by subcutaneous injection. In one embodiment, the nucleic acid e.g. siRNA agent is administered to the subject subcutaneously. The inhibitor e.g. nucleic acid e.g. siRNA can be delivered in a manner to target a particular tissue (e.g. in particular liver cells). METHODS FOR INHIBITING GENE EXPRESSION OR INHIBITION OF TARGET EXPRESSION OR FUNCTION IN VITRO The present invention also provides methods of inhibiting expression of SLC25A5 gene in a cell. The methods include contacting a cell with a nucleic acid of the invention e.g. siRNA agent, such as double stranded siRNA agent, in an amount effective to inhibit expression of the SLC25A5 gene in the cell, thereby inhibiting expression of the SLC25A5 gene in the cell. It is to be noted that a nucleic acid “for inhibiting the expression of SLC25A5” is a nucleic acid that is capable of inhibiting SLC25A5 expression, preferably as described herein below. Contacting of a cell with the nucleic acid e.g. an siRNA, such as a double stranded siRNA agent, may be done in vitro or in vivo. Contacting a cell in vivo with nucleic acid e.g. includes contacting a cell or group of cells within a subject, e.g., a human subject, with the nucleic acid e.g. siRNA. Combinations of in vitro and in vivo methods of contacting a cell are also possible. Contacting a cell may be direct or indirect, as discussed above. Furthermore, contacting a cell may be accomplished via a targeting ligand moiety, including any ligand moiety described herein or known in the art. In preferred embodiments, the targeting ligand moiety is a carbohydrate moiety, e.g. a GalNAc3 ligand, or any other ligand moiety that directs the siRNA agent to a site of interest. The term "inhibiting," as used herein, is used interchangeably with "reducing," "silencing," "downregulating", "suppressing", and other similar terms, and includes any level of inhibition. In some embodiments of the methods of the invention, expression or activity of a gene or an inhibition target is inhibited by at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, or to below the level of detection of the assay, preferably when determined by qPCR as described herein and/or when the siRNA is introduced into the target cell by transfection. In certain embodiments, the methods include a clinically relevant inhibition of expression of a target gene e.g. as demonstrated by a clinically relevant outcome after treatment of a subject with an agent to reduce the expression of the gene and/ or activity of the target. In some embodiments, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an IC50 value below a defined threshold value. In some embodiments, the threshold value may be 2500 pM, 2000 pM, 1900 pM, 1800 pM, 1700 pM, 1600 pM, 1500 pM, 1400 pM, 1300 pM, 1200 pM, 1100 pM, 1000 pM, 900 pM, 800 pM, 700 pM, 600 pM, 500 pM, 400 pM, 300 pM, 200 pM or 100 pM, preferably when determined by qPCR, more preferably by reverse transcriptase (RT)-qPCR, as described herein. In a preferred embodiment, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an IC50 value lower than 2500 pM. In a more preferred embodiment, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an IC50 value lower than 1000 pM. In an even more preferred embodiment, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an IC50 value lower than 500 pM. In a most preferred embodiment, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an IC50 value lower than 100 pM. Inhibition of the SLC25A5 gene may be quantified by the following method: Huh7 cells (human hepatocyte-derived cell line, obtained from JCRB Cell Bank) may be maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS and 1% non-essential amino acids at 37˚C in an atmosphere of 5% CO2. Cells may then be transfected with siRNA duplexes targeting SLC25A5 mRNA or a negative control siRNA (siRNA-control; sense strand 5’-_{GCCTGTACCAAGGCTTTAA}-3’ (SEQ ID NO: 1383), antisense strand 5’-_{TTAAAGCCTTGGTACAGGC}-3’ (SEQ ID NO: 1382)) using six 10-fold serial dilutions over a final duplex concentration range of 3 nM to 0.03 pM. Transfection may be carried out by adding 9.7 µL Opti-MEM (ThermoFisher) plus 0.3 µL Lipofectamine RNAiMAX (ThermoFisher) to 10 µL of each siRNA duplex. The mixture may be incubated at room temperature for 15 minutes before being added to 100 µL of complete growth medium containing 20,000 Huh7 cells. Cells may be incubated for 24 hours at 37˚C/5% CO2 prior to total RNA purification using a RNeasy 96 Kit (Qiagen). Each duplex may be tested by transfection in duplicate wells in a single experiment. cDNA synthesis may be performed using FastKing RT (with gDNase) Kit (Tiangen). Real-time quantitative PCR (qPCR) may be performed on an ABI Prism 7900HT or ABI QuantStudio 7 with primers specific for human SLC25A5 (forward: ACTGACATCATGTACACAGGCAC ^{(SEQ ID NO:1384)}, reverse: ACCCATGCCTCTGAGAACATT (SEQ ID NO:1385)^{) and} ^{human GAPDH (forward:} _{GAAGGTGAAGGTCGGAGTC (SEQ ID NO:1386)} ^{, reverse:} _{GAAGATGGTGATGGGATTTC (SEQ ID NO:1387)} ^{) using a SensiFAST SYBR Hi-ROX kit} (Meridian). qPCR may be performed in duplicate on cDNA derived from each well and the mean cycle threshold (Ct) calculated. Relative SLC25A5 expression may be calculated from mean Ct values using the comparative Ct (∆∆Ct) method, normalised to GAPDH and relative to untreated cells. Maximum percent inhibition of SLC25A5 expression and IC50 values may be calculated using a four parameter (variable slope) model using GraphPad Prism 9. In some embodiments, when transfected into the cells, the nucleic acid of the invention inhibits expression of the SLC25A5 gene with an pEC50 value lower than 5, 6, 7, 8, 9 or 10, preferably when determined by qPCR, more preferably by reverse transcriptase (RT)-qPCR, as described herein. For that, Huh7 cells (human hepatocyte-derived cell line, obtained from JCRB Cell Bank) may be maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS and 1% non-essential amino acids at 37˚C, 5% CO2, 95% humidity. Cells may be transfected with siRNA duplexes targeting either SLC25A5 mRNA or a negative control siRNA (siRNA- control; sense strand 5’-_{GCCTGTACCAAGGCTTTAA}-3’ (SEQ ID NO:1383), antisense strand 5’-_{TTAAAGCCTTGGTACAGGC}-3’ (SEQ ID NO:1382)) in a 6-point, log dose response curve to give final in assay concentrations of 3nM to 0.03pM. Transfection may be carried out by diluting Lipofectamine RNAiMAX (ThermoFisher) in Opti-MEM (ThermoFisher) medium at a ratio of 48.5:1.5. This solution may be added to an equal volume of siRNA, diluted to the required concentration in phosphate buffered saline. The lipofectamine RNAiMAX and siRNA mixture may be incubated at room temperature for 15 minutes before 20 µL may be added to wells of a 96 well plate. Huh7 cells may be dissociated from flasks using trypsin and resuspended at a density of 200,000 cells/mL.100 µL of Huh7 cell suspension may be added to each well of the siRNA-containing 96-well plates. Cells may be incubated for 24 hours at 37˚C, 5% CO2,95% humidity. Each siRNA may be tested in triplicate wells and on two separate days for a total of six replicates. Intracellular RNA may be isolated using an Rneasy kit (Qiagen) according to the manufacturer’s instructions. cDNA synthesis may be performed using a FastKing RT kit, with gDNase (Tiangen). Target cDNA may be the quantified by qPCR on an ABI Prism 7900HT or ABI QuantStudio 7 with primers specific for human SLC25A5 (forward: ACTGACATCATGTACACAGGCAC (SEQ ID NO:1384)_{, reverse:} _{ACCCATGCCTCTGAGAACATT (SEQ ID NO:1385)} ^{) and human GAPDH (forward:} GAAGGTGAAGGTCGGAGTC (SEQ ID NO:1386)^{, reverse:} _{GAAGATGGTGATGGGATTTC (SEQ ID NO:1387)} ^{) using a SensiFAST SYBR Hi-ROX kit} (Meridian). qPCR may be performed in duplicate on cDNA derived from each well and the mean Ct calculated. Relative SLC25A5 expression may be calculated from mean Ct values using the comparative Ct (∆∆Ct) method, normalised to GAPDH and relative to untreated cells. Maximum percent inhibition of SLC25A5 expression and pEC50 values (-log₁₀ of the EC50) may be calculated using a four parameter (variable slope) model using NumPy (Python). Alternatively or in addition, inhibition of expression of the SLC25A5 gene may be characterized by a reduction of mean relative expression of the SLC25A5 gene. In some embodiments, when cells are transfected with 0.1 nM of the nucleic acid of the invention, the mean relative expression of SLC25A5 is below 1, 0.9, 0.8, 0.7, 0.6, 0.5, or 0.4, preferably when determined by qPCR, more preferably by reverse transcriptase (RT)-qPCR, as described herein. In some embodiments, when cells are transfected with 5 nM of the nucleic acid of the invention, the mean relative expression of SLC25A5 is below 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4 or 0.3, preferably when determined by qPCR, more preferably by reverse transcriptase (RT)-qPCR, as described herein. Mean relative expression of the SLC25A5 gene may be quantified by the following method: Huh7 cells (human hepatocyte-derived cell line, obtained from JCRB Cell Bank) may be maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS at 37˚C in at atmosphere of 5% CO₂. Cells may be transfected with siRNA duplexes targeting SLC25A5 mRNA or a negative control siRNA (siRNA-control; sense strand 5’- _{GCCTGTACCAAGGCTTTAA}-3’ (SEQ ID NO:1383), antisense strand 5’- _{TTAAAGCCTTGGTACAGGC}-3’ (SEQ ID NO:1382)) at a final duplex concentration of 5 nM and 0.1 nM. Transfection may be carried out by adding 9.7 µL Opti-MEM (ThermoFisher) plus 0.3 µL Lipofectamine RNAiMAX (ThermoFisher) to 10 µL of each siRNA duplex. The mixture may be incubated at room temperature for 15 minutes before being added to 100 µL of complete growth medium containing 20,000 Huh7 cells. Cells may be incubated for 24 hours at 37˚C/5% CO₂ prior to total RNA purification using a Rneasy 96 Kit (Qiagen). Each duplex may be tested by transfection in duplicate wells in two independent experiments. cDNA synthesis may be performed using FastKing RT (with gDNase) Kit (Tiangen). Real-time quantitative PCR (qPCR) may be performed on an ABI Prism 7900HT or ABI QuantStudio 7 with primers specific for human SLC25A5 (forward: ACTGACATCATGTACACAGGCAC ^{(SEQ ID NO:1384)}, reverse: ACCCATGCCTCTGAGAACATT (SEQ ID NO:1385)^{) and} ^{human GAPDH (forward:} _{GAAGGTGAAGGTCGGAGTC (SEQ ID NO:1386)} ^{, reverse:} _{GAAGATGGTGATGGGATTTC (SEQ ID NO:1387)} ^{) using a SensiFAST SYBR Hi-ROX kit} (Meridian) . qPCR may be performed in duplicate on cDNA derived from each well and the mean Ct calculated. Relative SLC25A5 expression may be calculated from mean Ct values using the comparative Ct (∆∆Ct) method, normalised to GAPDH and relative to untreated cells. Inhibition of the expression of SLC25A5 gene may be manifested by a reduction of the amount of mRNA of the target SLC25A5 gene in comparison to a suitable control. In other embodiments, inhibition of the expression of SLC25A5 gene may be assessed in terms of a reduction of a parameter that is functionally linked to gene expression, e.g , protein expression or signaling pathways. METHODS OF TREATING OR PREVENTING DISEASES ASSOCIATED WITH GENE EXPRESSION/ EXPRESSION OF FUNCTION OF A TARGET The present invention also provides methods of using nucleic acid e.g. an siRNA of the invention or a composition containing nucleic acid e.g. an siRNA of the invention to reduce or inhibit gene expression in a cell or reduce expression or function of a target. The methods include contacting the cell with a nucleic acid e.g. dsiRNA of the invention and maintaining the cell for a time sufficient to obtain degradation of the mRNA transcript of a gene, thereby inhibiting expression of the gene in the cell. Reduction in gene expression or function of a target can be assessed by any methods known in the art. In a preferred embodiment, the gene is SLC25A5. In the methods of the invention the cell may be contacted in vitro or in vivo, i.e., the cell may be within a subject. A cell suitable for treatment using the methods of the invention may be any cell that expresses a gene of interest associated with a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or adipogenesis. The in vivo methods of the invention may include administering to a subject a composition containing a nucleic acid of the invention e.g. an siRNA, where the nucleic acid e.g. siRNA includes a nucleoside sequence that is complementary to at least a part of an RNA transcript of SLC25A5 gene of the mammal to be treated. The present invention further provides methods of treatment of a subject in need thereof. The treatment methods of the invention include administering a nucleic acid such as an siRNA of the invention to a subject, e.g., a subject that would benefit from a reduction or inhibition of the expression of a gene and/or expression and/or function of a target, in a therapeutically effective amount e.g. a nucleic acid such as an siRNA targeting a gene or a pharmaceutical composition comprising the nucleic acid targeting a gene. A nucleic acid e.g. siRNA of the invention may be administered as a "free” nucleic acid or “free” siRNA, administered in the absence of a pharmaceutical composition. The naked nucleic acid may be in a suitable buffer solution. The buffer solution may comprise acetate, citrate, prolamine, carbonate, or phosphate, or any combination thereof. In one embodiment, the buffer solution is phosphate buffered saline (PBS). The pH and osmolarity of the buffer solution can be adjusted such that it is suitable for administering to a subject. Alternatively, a nucleic acid e.g. siRNA of the invention may be administered as a pharmaceutical composition, such as a dsiRNA liposomal formulation. In one embodiment, the method includes administering a composition featured herein such that expression of the target gene is decreased, such as for about 1, 2, 3, 4, 5, 6, 7, 8, 12, 16, 18, 24 hours, 28, 32, or about 36 hours. In one embodiment, expression of the target gene is decreased for an extended duration, e.g., at least about two, three, four days or more, e.g., about one week, two weeks, three weeks, or four weeks or longer, e.g., about 1 month, 2 months, or 3 months. Subjects can be administered a therapeutic amount of nucleic acid e.g. siRNA, such as about 0.01 mg/kg to about 200 mg/kg. The nucleic acid e.g. siRNA can be administered by intravenous infusion over a period of time, on a regular basis. In certain embodiments, after an initial treatment regimen, the treatments can be administered on a less frequent basis. Administration of the siRNA can reduce gene product levels of a target gene , e.g., in a cell or tissue of the patient by at least about 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%, or below the level of detection of the assay method used. In certain embodiments, administration results in clinical stabilization or preferably clinically relevant reduction of at least one sign or symptom of a gene- associated disorder. Alternatively, the nucleic acid e.g. siRNA can be administered subcutaneously, i.e., by subcutaneous injection. One or more injections may be used to deliver the desired daily dose of nucleic acid e.g. s iRNA to a subject. The injections may be repeated over a period of time. The administration may be repeated on a regular basis. In certain embodiments, after an initial treatment regimen, the treatments can be administered on a less frequent basis. A repeat-dose regimen may include administration of a therapeutic amount of nucleic acid on a regular basis, such as every other day or to once a year. In certain embodiments, the nucleic acid is administered about once per month to about once per quarter (i.e., about once every three months). COMBINATION THERAPIES The inhibitor of the present invention may be combined with other therapeutic agents for use in therapy, in particular for use in treatment of any of the metabolic diseases or disorders disclosed herein. In certain embodiments, the inhibitor of the present invention, such as any of the siRNA molecules disclosed herein, may be combined with a GLP-1 agonist, including, without limitation, GLP-1/GIP dual agonists, GLP-1/FGF21 dual agonists, GLP-1/GCGR dual agonists and GLP-1/GIP/GCGR triple agonists, and/or a THR-beta agonist. That is, in certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1 agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1 agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term “GLP-1 agonist” as used herein refers to a compound, which fully or partially activates the human GLP-1 receptor. The term is thus equal to the term “GLP-1 receptor agonist” used in other documents. The term GLP-1 agonist as well as the specific GLP-1 agonists described herein also encompass salt forms thereof. It follows that the GLP-1 agonist should display “GLP-1 activity” which refers to the ability of the compound, i.e. a GLP-1 analogue or a compound comprising a GLP-1 analogue, to bind to the GLP-1 receptor and initiate a signal transduction pathway resulting in insulinotropic action or other physiological effects as is known in the art. In some embodiments the “GLP-1 agonist” binds to a GLP-1 receptor, e.g., with an affinity constant (KD) or activate the receptor with a potency (EC5o) of below 1 mM, e.g. below 100 nM as measured by methods known in the art (see e.g. WO 98/08871) and exhibits insulinotropic activity, where insulinotropic activity may be measured in vivo or in vitro assays known to those of ordinary skill in the art. For example, the GLP-1 agonist may be administered to an animal with increased blood glucose (e.g. obtained using an Intravenous Glucose Tolerance Test (IVGTT). A person skilled in the art will be able to determine a suitable glucose dosage and a suitable blood sampling regime, e.g. depending on the species of the animal, for the IVGTT) and measure the plasma insulin concentration overtime. Suitable assays have been described in such as WO 2015/155151. The term half maximal effective concentration (EC₅o) generally refers to the concentration which induces a response halfway between the baseline and maximum, by reference to the dose response curve. EC5o is used as a measure of the potency of a compound and represents the concentration where 50% of its maximal effect is observed. Due to the albumin binding effects of GLP-1 agonists comprising a substituent as described herein, it is important to pay attention to if the assay includes human serum albumin or not. The in vitro potency of the GLP-1 agonist may be determined as described in WO 2015/155151 , example 29 without Human Serum Albumin (HSA), and the EC5o determined. The lower the EC₅o value, the better the potency. In one embodiment, the potency (EC50) as determined (without HSA) is 5-1000 pM, such as 10-750 pM, 10-500 pM or 10-200 pM. In one embodiment the EC50 (without HSA) is at most 500 pM, such as at most 300 pM, such as at most 200 pM. In one embodiment the EC50 (without HSA) is comparable to human GLP-1 (7-37). In one embodiment the EC50 (without HSA) is at most 50 pM. In a further such embodiment the EC50 is at most 40 pM, such as at most 30 pM such as at most 20 pM, such as at most 10 pM. In one embodiment the EC50 is around 10 pM Also, or alternatively, the binding of the GLP-1 agonist to albumin may be measured using the in vitro potency assay of Example 29 of WO 2015/155151 including HSA. An increase of the in vitro potency, EC5o value, in the presence of serum albumin reflects the affinity to serum albumin. In one embodiment the potency (EC50) as determined (with 1 % HSA) is 5-1000 pM, such as 100-750 pM, 200-500 pM or 100-400 pM. In one embodiment the EC50 (with 1 % HSA) is at most 750 pM, such as at most 500 pM, such as at most 400 pM, such as at most 300 or such as at most 250 pM. If desired, the fold variation in relation to a known GLP-1 receptor agonist may be calculated as EC50(test analogue)/EC50(known analogue), and if this ratio is such as 0.5- 1.5, or 0.8-1.2 the potencies are considered to be equivalent. In one embodiment the potency, EC50 (without HSA), is equivalent to the potency of liraglutide. In one embodiment the potency, EC50 (without HSA), is equivalent to the potency of semaglutide. In some embodiments the GLP-1 agonist is a GLP-1 analogue, optionally comprising “one substituent”. The term "analogue" as used herein referring to a GLP-1 peptide (hereafter “peptide”) means a peptide wherein at least one amino acid residue of the peptide has been substituted with another amino acid residue and/or wherein at least one amino acid residue has been deleted from the peptide and/or wherein at least one amino acid residue has been added to the peptide and/or wherein at least one amino acid residue of the peptide has been modified. Such addition or deletion of amino acid residues may take place at the N- terminal of the peptide and/or at the C-terminal of the peptide. In some embodiments the term “GLP-1 analogue” or “analogue of GLP-1” as used herein refers to a peptide, or a compound, which is a variant of the human Glucagon-Like Peptide-1 (GLP-1 (7-37)). GLP-1 (7-37) has the sequence HAEGTFTSDV SSYLEGQAAKEFIAWLVKGRG (SEQ ID NO: 1388). In some embodiments the term “variant” refers to a compound which comprises one or more amino acid substitutions, deletions, additions and/or insertions. In one embodiment the GLP-1 agonist exhibits at least 60%, 65%, 70%, 80% or 90% sequence identity to GLP-1 (7-37) over the entire length of GLP-1 (7-37). In general, the term GLP-1 agonist is meant to encompass the GLP-1 agonist and any pharmaceutically acceptable salt, amide, or ester thereof. In some embodiments the composition comprises the GLP-1 agonist or a pharmaceutically acceptable salt, amide, or ester thereof. In some embodiments the composition comprises the GLP-1 agonist and one or more pharmaceutically acceptable counter ions. In certain embodiments, the inhibitor of the present invention, in particular the siRNA molecules of the present invention, may be administered with a GLP-1 agonist selected from one or more of the GLP-1 agonists disclosed in W093/19175, W096/29342, WO98/08871, WO99/43707, WO99/43706, W099/43341 , WO99/43708, W02005/027978, W02005/058954, W02005/058958, W02006/005667, W02006/037810, W02006/037811 , W02006/097537, W02006/097538, W02008/023050, W02009/030738, W02009/030771, W02009/030774 and WO2021/219710, which are incorporated herein by reference in their entirety. In certain embodiments, the inhibitor of the present invention, in particular the siRNA molecules of the present invention, may be administered with a GLP-1 agonist selected from the group consisting of: Dulaglutide (Trulicity®), Exenatide (Byetta®), Exenatide extended-release (Bydureon®), Liraglutide (Victoza®), Lixisenatide (Adlyxin®), Semaglutide injection (Ozempic®), and Semaglutide tablets (Rybelsus®). In some embodiments, the GLP-1 agonist is semaglutide having a formula of N- epsilon26-[2-(2- {2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxy-heptadecanoylamino)butyrylamino]ethoxy}ethoxy) acetylamino]ethoxy}ethoxy)acetyl] [Aib8,Arg34]GLP-1 (7-37). The term “GLP-1 agonist” as used herein also encompasses dual or triple agonists that can activate more than one receptor. These dual or triple agonists may be molecules that have the ability to activate the GLP-1 receptor and at least one further receptor. In some embodiments, the dual or triple agonist may be a chimeric molecule comprising a first portion that activates the GLP-1 receptor and further portions that activate further receptors. In certain embodiments, the GLP-1 agonist is a dual or triple agonist that, in addition to the GLP-1 receptor, further activates one or more of: a glucose-dependent insulinotropic polypeptide (GIP) receptor, a Fibroblast growth factor 21 (FGF21) receptor, and a glucagon receptor (GCGR). In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/GIP dual agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/GIP dual agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term "GLP-1/GIP dual agonist" as used in the context of the present invention refers to a substance or ligand that can activate the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. GLP-1/GIP receptor co-agonists and their potential medical uses are described in several patent applications such as WO 2010/011439, WO 2013/164483, WO 2014/192284, WO 2015/067715, WO 2015/022420, WO 2015/086728, WO 2015/086729, WO 2016/111971, WO 2020/023386, US 9745360, US 2014/162945, US 2014/0357552, WO 2021/150673, WO 2021/260530, WO 2022/018185, and WO 2022/079639, which are fully incorporated herein by reference. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with the GLP-1/GIP dual agonist tirzepatide (Mounjaro®) for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with the GLP-1/GIP dual agonist tirzepatide (Mounjaro®) for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. As used herein, “tirzepatide” means a GLP-1/GIP dual agonist peptide as described in U.S. Pat. No.9,474,780 and described by CAS Registry Number: 2023788-19-2. Tirzepatide is described in Example 1 of U.S. Pat. No.9,474,780, with the following sequence: YX₁EGTFTSDYSIX₂LDKIAQKAFVQWLMGGPSSGAPPPS (SEQ ID NO: 1389) wherein X₁ is α-amino isobutyric acid (Aib); X₂ is Aib; K at position 20 is chemically modified through conjugation to the epsilon-amino group of the K side-chain with (2-[2-(2-Amino- ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO—(CH2)18—CO2H; and the C-terminal amino acid is amidated as a C-terminal primary amide. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/ FGF21 dual agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/FGF21 dual agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term "GLP-1/FGF21 dual agonist" as used in the context of the present invention refers to a substance or ligand that can activate the GLP-1 receptor and the Fibroblast growth factor 21 (FGF21) receptor. Preferably, the GLP-1/FGF21 dual agonist is a chimeric molecule comprising a GLP-1 agonist as defined herein above and the molecule FGF21 or a functionally active variant or analogue thereof. In certain embodiments, the GLP-1/FGF21 dual agonist may further comprise an antibody Fc region. GLP-1/ FGF21 receptor co-agonists and their potential medical uses are described in several patent applications such as WO 2010/142665, WO2014/037373, WO 2018/115401, WO 2018/166461, WO 2019/243557, and WO 2022/002408, which are fully incorporated herein by reference. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/ GCGR dual agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/GCGR dual agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term "GLP-1/ GCGR dual agonist" as used in the context of the present invention refers to a substance or ligand that can activate the GLP-1 receptor and the glucagon receptor (GCGR). GLP-1/GCGR receptor co-agonists and their potential medical uses are described in several patent applications such as, WO 2008/101017, WO 2009/155258, WO 2011/075393, WO 2011/160630, WO 2014/056872, WO 2014/091316, WO 2015/086733, WO 2017/181452, WO 2018/100174, WO 2019/030268, WO 2019/060660 and WO 2023/006923, which are fully incorporated herein by reference. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with the GLP-1/ GCGR dual agonist Survodutide (BI 456906) for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with the GLP-1/ GCGR dual agonist Survodutide (BI 456906) for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/GIP/GCGR triple agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1/GIP/GCGR dual agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term " GLP-1/GIP/GCGR triple agonist” as used in the context of the present invention refers to a substance or ligand that can activate the GLP-1 receptor, the GIP receptor and the glucagon receptor (GCGR). GLP-1/GIP/GCGR receptor co-agonists and their potential medical uses are described in several patent applications such as, WO 2014/096150, WO 2015/067716, WO 2019/125292, WO 2022/090447, and WO 2022/268029, which are fully incorporated herein by reference. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with Retatrutid (LY-3437943) for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with Retatrutid (LY-3437943) for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The person skilled in the art is aware of ways to formulate GLP-1 agonists, including dual and triple agonists, for any suitable route of administration. In certain embodiments, the GLP-1 agonist may be administered orally or by injection, e.g., by subcutaneous injection. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a THR-beta agonist for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a THR-beta agonist for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The term “THR-beta agonist” as used herein refers to a compound, which fully or partially activates the human thyroid hormone receptor-β. The term THR-beta agonist as well as the specific THR-beta agonists described herein also encompass salt forms thereof. Various THR-beta agonists have been described in the art and have been summarized, inter alia, by Zucchi (Thyroid Hormone Analogues: An Update, Thyroid. August 2020; 30(8): 1099–1105), which is incorporated herein by reference in its entirety. In certain embodiments, the THR-beta agonist that is to be administered in combination with the inhibitor of the invention is MGL-3196 (resmetirom), KB-2115 (eprotirome), GC-1 (sobetirome) or MB07344/VK2809, as, for example, described by Zucchi. In certain embodiments, the THR-beta agonist is MGL-3196 (resmetirom) or any of the compounds disclosed in WO 2014/043706, which is incorporated herein by reference in its entirety. Resmetirom is a thyroid hormone receptor (THR) β-selective agonist. Disclosures related to resmetirom can further be found in US Patent No.9,266,861, US Patent Application Serial No.16/343,065, and PCT Application Serial No. PCT/US2019/040276, the contents of each of which are incorporated herein by reference in their entireties. In certain embodiments, the THR-beta agonist is KB-2115 (eprotirome) or any of the compounds disclosed in WO 2007/110226 or WO 2009/077147, which are incorporated herein by reference in their entirety. The person skilled in the art is aware of ways to formulate THR-beta agonists for any suitable route of administration. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1 agonist, such as any one of the GLP-1 agonists disclosed herein above, including dual or triple agonists, and a THR-beta agonist, such as any one of the THR-beta agonists disclosed herein above, for the treatment of metabolic diseases or disorders. In a particular embodiment, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be combined with a GLP-1 agonist, such as any one of the GLP-1 agonists disclosed herein above, including dual or triple agonists, and a THR-beta agonist, such as any one of the THR-beta agonists disclosed herein above, for the treatment of fatty liver diseases, in particular NAFLD and/or NASH. The inhibitor of the invention, in particular the siRNA molecules disclosed herein, may alternatively, or in addition, be combined and/or co-administered with one or more of: an amylin receptor agonist (such as pramlintide), and/or a dual amylin + calcitonin receptor agonist, and/or a glucagon receptor agonist, and/or an FXR receptor agonist (such as cilofexor or obeticholic acid), and/or an FGF-21 analogue or FGF-21 receptor agonist (such as efruxifermin), and/or an FGF-19 analogue or FGF-19 receptor agonist (such as aldafermin), and/or a galectin 3 inhibitor (such as belapectin), and/or a PPAR ^ agonist (such as elafibrinor), and/or a PPAR ^ agonist (such as pioglitazone or rosiglitazone), and/or a mixed PPAR ^ and/or ^ and/or ^ agonist, and/or a pan PPAR ^ ^ ^ agonist (such as lanafibranor), and/or an acetyl CoA desaturase activator, and/or an ASK1 inhibitor (such as selonsertib), and/or an LOXL2 inhibitor (such as simtuzumab), and/or a dual CCR2/5 inhibitor (such as cenicriviroc), and/or an inhibitor of an enzyme in the de novo lipogenesis (DNL) pathway including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and/or an inhibitor of an enzyme in the cholesterol biosynthesis pathway (such as an HMGCoA reductase inhibitor, such as atorvastatin); preferably for the treatment of any of the metabolic diseases or disorders disclosed herein, more preferably for the treatment of NAFLD. In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be used for the treatment of any of the metabolic diseases or disorders disclosed herein, more preferably for the treatment of NAFLD, in combination with any of the molecules disclosed in Fig.1 of Nathani and Bansal (Gastroenterol Hepatol (NY).2023 Jul; 19(7): 371–381; incorporated by reference), in particular one or more of: a THR-beta agonist (such as resmetirom, VK2809 or TERN-501), a PPAR agonist (such as Lanifibranor, Saroglitazar, or Elafibranor), a GLP-1 agonist (such as Liraglutide, Semaglutide or Tirzepatide), a CCR2/5 inhibitor (such as Cenicriviroc), an ASK1 inhibitor (such as Selonsertib), an ACC inhibitor (such as Firsocostat or PF-05221304), an SCD inhibitor (such as Aramchol), an FGF21 analogue (such as Efruxifermin or Pegbelfermin), a Galectin-3 inhibitor (such as Belapectin), a LOXL2 inhibitor (such as Simtuzumab), an FXR agonists (such as Obeticholic acid, Tropifexor, Cilofexor, EDP-305, or MET409), and/or an FGF19 analogue (such as Aldafermina). In certain embodiments, the inhibitor of the invention, in particular the siRNA molecules disclosed herein, may be used for the treatment of any of the metabolic diseases or disorders disclosed herein, more preferably for the treatment of NAFLD, in combination with any of the molecules disclosed in Batchuluun et al. (Nat Rev Drug Discov, 2022, 21(4):283-305. doi: 10.1038/s41573-021-00367-2.; incorporated by reference), in particular one or more of: a citrate/isocitrate carrier (CIC) inhibitor (such as Benzenetricarboxylate, CPTI-1 or CPTI-2), an ATP-citrate lyase (ACLY) inhibitor (such as Bempedoic acid, Hydroxycitrate, BMS-303141, Emodin derivates, Furan carboxylate derivates, MEDICA 16, SB-204990, or NDI-091143), an acetyl-CoA carboxylase (ACC) inhibitor (such as Firsocostat, PF-05221304, PF-05175157, MK- 4074, A-908292, Carboxamide derivative-1k, CP-640186, Monocyclic derivate-1q, ND-654, ND-646, Olefin derivate-2e, (S)-9c, Soraphen A, TOFA, or WZ66), and/or a fatty acid synthase (FAS) inhibitor (such as Orlistat, TVB-2640, FT-4101, BI-99179, Cerulenin, C75, Fasnall, GSK2194069, IPI-9119, MP-ML-24-N1, or TVB-3166). A combination therapy, or a “combination” contemplated herein includes the co-administration of an inhibitor according to the invention, in particular an siRNA according to the invention, with one or more additional therapeutic agent, preferably one or more of the additional therapeutic agents disclosed herein above. The inhibitor according to the invention may be administered prior to, after, or at the same time as the one or more additional therapeutic agent. In certain embodiments, the inhibitor according to the invention, in particular the siRNA according to the invention, may be co-administered with a GLP-1 agonist, including GLP-1/GIP dual agonists, GLP-1/FGF21 dual agonists, GLP-1/GCGR dual agonists and GLP-1/GIP/GCGR triple agonists, and/or a THR-beta agonist, wherein the inhibitor according to the invention may be administered prior to, after, or at the same time as the GLP-1 agonist and/or the THR-beta agonist. In an exemplary embodiment, the co-administration includes administering an siRNA according to the invention and any of the GLP-1 agonists, including GLP-1/GIP dual agonists, GLP- 1/FGF21 dual agonists, GLP-1/GCGR dual agonists and GLP-1/GIP/GCGR triple agonists, disclosed herein or incorporated herein by reference. In another exemplary embodiment, the co- administration includes administering an siRNA according to the invention and the GLP-1 agonist semaglutide. In another exemplary embodiment, the co-administration includes administering an siRNA according to the invention and the GLP-1/GIP dual agonist terzapetide. In yet another exemplary embodiment, the co-administration includes administering an siRNA according to the invention and any of the THR-beta agonists disclosed herein or incorporated herein by reference. In another exemplary embodiment, the co-administration includes administering an siRNA according to the invention and the THR-beta agonist resmetirom. In another exemplary embodiment, the co-administration includes administering an siRNA according to the invention, the GLP-1 agonists semaglutide or terzapetide, and the THR-beta agonist resmetirom. The combination therapy of the disclosure comprising the inhibitor according to the invention and at least one more additional therapeutic agent may be administered via any route. In some embodiments, the inhibitor according to the invention and the at least one more additional therapeutic agent may be delivered orally, subcutaneously, intravenously, intranasally, transdermally, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly. In exemplary embodiments, the inhibitor according to the invention may be administered intravenously (IV) and/or subcutaneously, and the GLP-1 agonist may be administered subcutaneously. In one aspect the present invention may be applied in the compounds, processes, compositions or uses of the following Sentences numbered 1-101 wherein reference to any Formula in the Sentences 1-101 refers only to those Formulas that are defined within Sentences 1-101. These formulae are reproduced in Figure 6. Specifically, an oligonucleoside moiety as represented by Z in any of the following sentences can comprise a nucleic acid for inhibiting expression of SLC25A5 as defined in any of the claims hereinafter. 1. A compound comprising the following structure:

Formula (I) wherein: R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1-3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; m is an integer of from 1 to 6; n is an integer of from 1 to 10; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety. 2. A compound according to Sentence 1, wherein R1 is hydrogen at each occurrence. 3. A compound according to Sentence 1, wherein R1 is methyl. 4. A compound according to Sentence 1, wherein R₁ is ethyl. 5. A compound according to any of Sentences 1 to 4, wherein R₂ is hydroxy. 6. A compound according to any of Sentences 1 to 4, wherein R2 is halo. 7. A compound according to Sentence 6, wherein R₂ is fluoro. 8. A compound according to Sentence 6, wherein R₂ is chloro. 9. A compound according to Sentence 6, wherein R2 is bromo. 10. A compound according to Sentence 6, wherein R2 is iodo. 11. A compound according to Sentence 6, wherein R₂ is nitro. 12. A compound according to any of Sentences 1 to 11, wherein X1 is methylene. 13. A compound according to any of Sentences 1 to 11, wherein X1 is oxygen. 14. A compound according to any of Sentences 1 to 11, wherein X₁ is sulfur. 15. A compound according to any of Sentences 1 to 14, wherein X2 is methylene. 16. A compound according to any of Sentences 1 to 15, wherein X2 is oxygen. 17. A compound according to any of Sentences 1 to 16, wherein X₂ is sulfur. 18. A compound according to any of Sentences 1 to 17, wherein m = 3. 19. A compound according to any of Sentences 1 to 18, wherein n = 6. 20. A compound according to Sentences 13 and 15, wherein X1 is oxygen and X2 is methylene, and preferably wherein: q = 1, r = 2, s = 1, t = 1, v = 1. 21. A compound according to Sentences 12 and 15, wherein both X₁ and X₂ are methylene, and preferably wherein: q = 1, r = 3, s = 1, t = 1, v = 1. 22. A compound according to any of Sentences 1 to 21, wherein Z is:

wherein: Z1, Z2, Z3, Z4 are independently at each occurrence oxygen or sulfur; and one the bonds between P and Z2, and P and Z3 is a single bond and the other bond is a double bond. 23. A compound according to Sentence 22, wherein said oligonucleoside is an RNA compound capable of modulating, preferably inhibiting, expression of a target gene. 24. A compound according to Sentence 23, wherein said RNA compound comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends. 25. A compound according to Sentence 24, wherein the RNA compound is attached at the 5’ end of its second strand to the adjacent phosphate. 26. A compound according to Sentence 24, wherein the RNA compound is attached at the 3’ end of its second strand to the adjacent phosphate. 27. A compound of Formula (II):

Formula (II) 28. A compound of Formula (III):

Formula (III) 29. A compound according to Sentence 27 or 28, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 30. A composition comprising a compound of Formula (II) as defined in Sentence 27, and a compound of Formula (III) as defined in Sentence 28, optionally dependent on Sentence 29. 31. A composition according to Sentence 30, wherein said compound of Formula (III) as defined in Sentence 28 is present in an amount in the range of 10 to 15% by weight of said composition. 32. A compound of Formula (IV): Formula (IV) 33. A compound of Formula (V):

Formula (V) 34. A compound according to Sentence 32 or 33, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 35. A composition comprising a compound of Formula (IV) as defined in Sentence 32, and a compound of Formula (V) as defined in Sentence 33, optionally dependent on Sentence 34. 36. A composition according to Sentence 35, wherein said compound of Formula (V) as defined in Sentence 33 is present in an amount in the range of 10 to 15% by weight of said composition. 37. A compound as defined in any of Sentences 1 to 29, or 32 to 34, wherein the oligonucleoside comprises an RNA duplex which further comprises one or more riboses modified at the 2’ position, preferably a plurality of riboses modified at the 2’ position. 38. A compound according to Sentence 37, wherein the modifications are chosen from 2’-O- methyl, 2’-deoxy-fluoro, and 2’-deoxy. 39. A compound according to any of Sentences 1 to 29, or 32 to 34, or 37 to 38, wherein the oligonucleoside further comprises one or more degradation protective moieties at one or more ends. 40. A compound according to Sentence 39, wherein said one or more degradation protective moieties are not present at the end of the oligonucleoside strand that carries the ligand moieties, and / or wherein said one or more degradation protective moieties is selected from phosphorothioate internucleoside linkages, phosphorodithioate internucleoside linkages and inverted abasic nucleosides, wherein said inverted abasic nucleosides are present at the distal end of the strand that carries the ligand moieties. 41. A compound according to any of Sentences 1 to 29, or 32 to 34, or 37 to 40, wherein said ligand moiety as depicted in Formula (I) in Sentence 1 comprises one or more ligands. 42. A compound according to Sentence 41, wherein said ligand moiety as depicted in Formula (I) in Sentence 1 comprises one or more carbohydrate ligands. 43. A compound according to Sentence 42, wherein said one or more carbohydrates can be a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide or polysaccharide. 44. A compound according to Sentence 43, wherein said one or more carbohydrates comprise one or more galactose moieties, one or more lactose moieties, one or more N- AcetylGalactosamine moieties, and / or one or more mannose moieties. 45. A compound according to Sentence 44, wherein said one or more carbohydrates comprise one or more N-Acetyl-Galactosamine moieties. 46. A compound according to Sentence 45, which comprises two or three N- AcetylGalactosamine moieties. 47. A compound according to any of Sentences 41 to 46, wherein said one or more ligands are attached in a linear configuration, or in a branched configuration. 48. A compound according to Sentence 47, wherein said one or more ligands are attached as a biantennary or triantennary branched configuration. 49. A compound according to Sentences 46 to 48, wherein said moiety: as depicted in Formula (I) in Sentence 1 is any of Formulae (VIa), (VIb) or (VIc), preferably Formula (VIa):

Formula (VIa) wherein: AI is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and b is an integer of 2 to 5; or

Formula (VIc) wherein: A_I is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and e is an integer of 2 to 10. 50. A compound according to Sentences 46 to 48, wherein said moiety:

as depicted in Formula (I) in Sentence 1 is Formula (VII):

Formula (VII) wherein: AI is hydrogen; a is an integer of 2 or 3. 51. A compound according to Sentence 49 or 50, wherein a = 2. 52. A compound according to Sentence 49 or 50, wherein a = 3. 53. A compound according to Sentence 49, wherein b = 3. 54. A compound of Formula (VIII):

Formula (VIII)

Formula (IX) 56. A compound according to Sentence 54 or 55, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 57. A composition comprising a compound of Formula (VIII) as defined in Sentence 54, and a compound of Formula (IX) as defined in Sentence 55, optionally dependent on Sentence 56. 58. A composition according to Sentence 57, wherein said compound of Formula (IX) as defined in Sentence 55 is present in an amount in the range of 10 to 15% by weight of said composition. 59. A compound of Formula (X):

Formula (X) 60. A compound of Formula (XI):

Formula (XI) 61. A compound according to Sentence 59 or 60, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 62. A composition comprising a compound of Formula (X) as defined in Sentence 59, and a compound of Formula (XI) as defined in Sentence 60, optionally dependent on Sentence 61. A composition according to Sentence 62, wherein said compound of Formula (XI) as defined in Sentence 60 is present in an amount in the range of 10 to 15% by weight of said composition. A compound as defined in any of Sentences 54 to 63, wherein the oligonucleoside comprises an RNA duplex which further comprises one or more riboses modified at the 2’ position, preferably a plurality of riboses modified at the 2’ position. A compound according to Sentence 64, wherein the modifications are chosen from 2’-O- methyl, 2’-deoxy-fluoro, and 2’-deoxy. A compound according to any of Sentences 54 to 65, wherein the oligonucleoside further comprises one or more degradation protective moieties at one or more ends. A compound according to Sentence 66, wherein said one or more degradation protective moieties are not present at the end of the oligonucleoside strand that carries the ligand moieties, and / or wherein said one or more degradation protective moieties is selected from phosphorothioate internucleoside linkages, phosphorodithioate internucleoside linkages and inverted abasic nucleosides, wherein said inverted abasic nucleosides are present at the distal end of the strand that carries the ligand moieties, as shown in any of Formulae (VIII), (IX), (X) or (XI) in any of Sentences 54, 55, 59 or 60. A process of preparing a compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62, 63, which comprises reacting compounds of Formulae (XII) and (XIII):

Formula (XII) Formula (XIII) herein: R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1-3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; m is an integer of from 1 to 6; n is an integer of from 1 to 10; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety; and where appropriate carrying out deprotection of the ligand and / or annealing of a second strand for the oligonucleoside moiety. 69. A process according to Sentence 68, wherein a compound of Formula (XII) is prepared by reacting compounds of Formulae (XIV) and (XV):

Formula (XIV)

Formula (XV) R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R2 is selected from the group consisting of hydrogen, hydroxy, -OC1-3alkyl, -C(=O)OC1-3alkyl, halo and nitro; X₁ and X₂ at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety. 70. A process according to Sentence 68, to prepare a compound according to any of Sentences 20, 25, 27, 29, 54, 56, and / or a composition according to any of Sentences 30, 31, 57, 58, wherein: compound of Formula (XII) is Formula (XIIa):

Formula (XIIa) and compound of Formula (XIII) is Formula (XIIIa):

Formula (XIIIa) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 71. A process according to Sentence 68, to prepare a compound according to any of Sentences 20, 25, 28, 29, 55, 56, and / or a composition according to any of Sentences 30, 31, 57, 58, wherein: compound of Formula (XII) is Formula (XIIb):

Formula (XIIb) and compound of Formula (XIII) is Formula (XIIIa):

Formula (XIIIa) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 72. A process according to Sentence 68, to prepare a compound according to any of Sentences 21, 26, 32, 34, 59, 61, and / or a composition according to any of Sentences 35, 36, 62, 63, wherein: compound of Formula (XII) is Formula (XIIc):

Formula (XIIc) and compound of Formula (XIII) is Formula (XIIIa):

Formula (XIIIa) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 73. A process according to Sentence 68, to prepare a compound according to any of Sentences 21, 26, 33, 34, 60, 61, and / or a composition according to any of Sentences 35, 36, 62, 63, wherein: compound of Formula (XII) is Formula (XIId): Formula (XIId) and compound of Formula (XIII) is Formula (XIIIa):

Formula (XIIIa) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 74. A process according to any of Sentences 70 to 73, wherein: compound of Formula (XIIIa) is Formula (XIIIb):

Formula (XIIIb) 75. A process according to Sentences 69, as dependent on Sentences 70 to 73, wherein: compound of Formula (XIV) is either Formula (XIVa) or Formula (XIVb):

Formula (XIVb) and compound of Formula (XV) is either Formula (XVa) or Formula (XIVb):

Formula (XVa)

Formula (XVb) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein (i) said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate in Formula (XVa), or (ii) said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate in Formula (XVb). 76. A compound of Formula (XII):

Formula (XII) wherein: R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1-3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety. 77. A compound of Formula (XIIa): Formula (XIIa) 78. A compound of Formula (XIIb):

Formula (XIIb) 79. A compound of Formula (XIIc):

Formula (XIIc) 80. A compound of Formula (XIId):

Formula (XIId) 81. A compound of Formula (XIII):

Formula (XIII) wherein: R1 at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; m is an integer of from 1 to 6; n is an integer of from 1 to 10. 82. A compound of Formula (XIIIa):

Formula (XIIIa) 83. A compound of Formula (XIIIb):

Formula (XIIIb) 84. A compound of Formula (XIV): Formula (XIV) wherein: R₁ is selected from the group consisting of hydrogen, methyl and ethyl; R₂ is selected from the group consisting of hydrogen, hydroxy, -OC_1-3alkyl, -C(=O)OC_1-3alkyl, halo and nitro; X₂ is selected from the group consisting of methylene, oxygen and sulfur; s, t, v are independently integers from 0 to 4, with the proviso that s, t and v cannot all be 0 at the same time. 85. A compound of Formula (XIVa):

Formula (XIVa) 86. A compound of Formula (XIVb):

Formula (XIVb) 87. A compound of Formula (XV): Formula (XV) wherein: R₁ at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; X1 is selected from the group consisting of methylene, oxygen and sulfur; q and r are independently integers from 0 to 4, with the proviso that q and r cannot both be 0 at the same time; Z is an oligonucleoside moiety. 88. A compound of Formula (XVa):

Formula (XVa) 89. A compound of Formula (XVb):

Formula (XVb) 90. Use of a compound according to any of Sentences 76, 81 to 84, 87, for the preparation of a compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62 and 63. 91. Use of a compound according to Sentence 85, for the preparation of a compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62 and 63, wherein R2 = F. 92. Use of a compound according to Sentence 86, for the preparation of a compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62 and 63, wherein R₂ = OH. 93. Use of a compound according to Sentence 77, for the preparation of a compound according to any of Sentences 20, 25, 27, 29, 54, 56, and / or a composition according to any of Sentences 30, 31, 57, 58. 94. Use of a compound according to Sentence 78, for the preparation of a compound according to any of Sentences 20, 25, 28, 29, 55, 56, and / or a composition according to any of Sentences 30, 31, 57, 58. 95. Use of a compound according to Sentence 79, for the preparation of a compound according to any of Sentences 21, 26, 32, 34, 59, 61, and / or a composition according to any of Sentences 35, 36, 62, 63. 96. Use of a compound according to Sentence 80, for the preparation of a compound according to any of Sentences 21, 26, 33, 34, 60, 61, and / or a composition according to any of Sentences 35, 36, 62, 63. 97. Use of a compound according to Sentence 88, for the preparation of a compound according to any of Sentences 20, 25, 27 to 29, 54 to 56, and / or a composition according to any of Sentences 30, 31, 57, 58. 98. Use of a compound according to Sentence 89, for the preparation of a compound according to any of Sentences 21, 26, 32 to 34, 59 to 61, and / or a composition according to any of Sentences 35, 36, 62, 63. 99. A compound or composition obtained, or obtainable by a process according to any of Sentences 68 to 75. 100. A pharmaceutical composition comprising of a compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62 and 63, together with a pharmaceutically acceptable carrier, diluent or excipient. 101. A compound according to any of Sentences 1 to 29, 32 to 34, 37 to 56, 59 to 61, and 64 to 67, and / or a composition according to any of Sentences 30, 31, 35, 36, 57, 58, 62 and 63, for use in therapy. In another aspect the present invention may be applied in the compounds, processes, compositions or uses of the following Clauses numbered 1-56 wherein reference to any Formula in the Clauses refers only to those Formulas that are defined within Clause 1-56. These formulae are reproduced in Figure 7. Specifically, an oligonucleoside moiety as represented by Z in any of the following clauses can comprise a nucleic acid for inhibiting expression of SLC25A5 as defined in any of the claims hereinafter. 1. A compound comprising the following structure:

Formula (I*) wherein: r and s are independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety. 2. A compound according to Clause 1, wherein s is an integer selected from 4 to 12. 3. A compound according to Clause 2, wherein s is 6. 4. A compound according to any of Clauses 1 to 3, wherein r is an integer selected from 4 to 14. 5. A compound according to Clause 4, wherein r is 6. 6. A compound according to Clause 4, wherein r is 12. 7. A compound according to Clause 5, which is dependent on Clause 3. 8. A compound according to Clause 6, which is dependent on Clause 3. 9. A compound according to any of Clauses 1 to 8, wherein Z is: wherein: Z1, Z2, Z3, Z4 are independently at each occurrence oxygen or sulfur; and one the bonds between P and Z₂, and P and Z₃ is a single bond and the other bond is a double bond. 10. A compound according to any of Clauses 1 to 9, wherein said oligonucleoside is an RNA compound capable of modulating, preferably inhibiting, expression of a target gene. 11. A compound according to any of Clause 10, wherein said RNA compound comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends. 12. A compound according to Clause 11, preferably also dependent on Clauses 3 and 6, wherein the RNA compound is attached at the 5’ end of its second strand to the adjacent phosphate. 13. A compound according to Clause 11, preferably also dependent on Clauses 3 and 5, wherein the RNA compound is attached at the 3’ end of its second strand to the adjacent phosphate. 14. A compound of Formula (II*), preferably dependent on Clause 12:

Formula (II*) 15. A compound of Formula (III*), preferably dependent on Clause 13: Formula (III*) 16. A compound as defined in any of Clauses 1 to 15, wherein the oligonucleoside comprises an RNA duplex which further comprises one or more riboses modified at the 2’ position, preferably a plurality of riboses modified at the 2’ position. 17. A compound according to Clause 16, wherein the modifications are chosen from 2’-O- methyl, 2’-deoxy-fluoro, and 2’-deoxy. 18. A compound according to any of Clauses 1 to 17, wherein the oligonucleoside further comprises one or more degradation protective moieties at one or more ends. 19. A compound according to Clause 18, wherein said one or more degradation protective moieties are not present at the end of the oligonucleoside strand that carries the linker / ligand moieties, and / or wherein said one or more degradation protective moieties is selected from phosphorothioate internucleoside linkages, phosphorodithioate internucleoside linkages and inverted abasic nucleosides, wherein said inverted abasic nucleosides are present at the distal end of the same strand to the end that carries the linker / ligand moieties. 20. A compound according to any of Clauses 1 to 19, wherein said ligand moiety as depicted in Formula (I*) in Clause 1 comprises one or more ligands. 21. A compound according to Clause 20, wherein said ligand moiety as depicted in Formula (I*) in Clause 1 comprises one or more carbohydrate ligands. 22. A compound according to Clause 21, wherein said one or more carbohydrates can be a monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide or polysaccharide. 23. A compound according to Clause 22, wherein said one or more carbohydrates comprise one or more galactose moieties, one or more lactose moieties, one or more N- AcetylGalactosamine moieties, and / or one or more mannose moieties. 24. A compound according to Clause 23, wherein said one or more carbohydrates comprise one or more N-Acetyl-Galactosamine moieties. 25. A compound according to Clause 24, which comprises two or three N- AcetylGalactosamine moieties. 26. A compound according to any of the preceding Clauses, wherein said one or more ligands are attached in a linear configuration, or in a branched configuration. 27. A compound according to Clause 26, wherein said one or more ligands are attached as a biantennary or triantennary branched configuration. 28. A compound according to Clauses 20 to 27, wherein said moiety:

as depicted in Formula (I*) in Clause 1 is any of Formulae (IV*), (V*) or (VI*), preferably Formula (IV*):

Formula (VI*) wherein: AI is hydrogen, or a suitable hydroxy protecting group; a is an integer of 2 or 3; and e is an integer of 2 to 10. 29. A compound according to any of Clauses 1 to 28, wherein said moiety: as depicted in Formula (I*) in Clause 1 is Formula (VII*):

Formula (VII*) wherein: A_I is hydrogen; a is an integer of 2 or 3. 30. A compound according to Clause 28 or 29, wherein a = 2. 31. A compound according to Clause 28 or 29, wherein a = 3. 32. A compound according to Clause 28, wherein b = 3. 33. A compound of Formula (VIII*):

Formula (VIII*) 34. A compound of Formula (IX*): Formula (IX*) 35. A compound according to Clause 33 or 34, wherein the oligonucleoside comprises an RNA duplex which further comprises one or more riboses modified at the 2’ position, preferably a plurality of riboses modified at the 2’ position. 36. A compound according to Clause 35, wherein the modifications are chosen from 2’-O- methyl, 2’-deoxy-fluoro, and 2’-deoxy. 37. A compound according to any of Clauses 33 to 36, wherein the oligonucleoside further comprises one or more degradation protective moieties at one or more ends. 38. A compound according to Clause 37, wherein said one or more degradation protective moieties are not present at the end of the oligonucleoside strand that carries the linker / ligand moieties, and / or wherein said one or more degradation protective moieties is selected from phosphorothioate internucleoside linkages, phosphorodithioate internucleoside linkages and inverted abasic nucleosides, wherein said inverted abasic nucleosides are present at the distal end of the same strand to the end that carries the linker / ligand moieties. 39. A compound according to Clause 33, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 40. A compound according to Clause 34, wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 41. A process of preparing a compound according to any of Clauses 1 to 40, which comprises reacting compounds of Formulae (X*) and (XI*):

Formula (X*)

Formula (XI*) wherein: r and s are independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety; and where appropriate carrying out deprotection of the ligand and / or annealing of a second strand for the oligonucleoside. 42. A process according to Clause 41, to prepare a compound according to any of Clauses 6, 8 to 14, 16 to 33, and 35 to 40, wherein: compound of Formula (X*) is Formula (Xa*): Formula (Xa*) and compound of Formula (XI*) is Formula (XIa*):

Formula (XIa*) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 5’ end of its second strand to the adjacent phosphate. 43. A process according to Clause 41, to prepare a compound according to any of Clauses 5, 7, 9 to 13, 15 to 32, and 34 to 40, wherein: compound of Formula (X*) is Formula (Xb*):

Formula (Xb*) and compound of Formula (XI*) is Formula (XIa*):

Formula (XIa*) wherein the oligonucleoside comprises an RNA duplex comprising first and second strands, wherein the first strand is at least partially complementary to an RNA sequence of a target gene, and the second strand is at least partially complementary to said first strand, and wherein each of the first and second strands have 5’ and 3’ ends, and wherein said RNA duplex is attached at the 3’ end of its second strand to the adjacent phosphate. 44. A process according to Clauses 42 or 43, wherein: compound of Formula (XIa*) is Formula (XIb*):

Formula (XIb*) 45. A compound of Formula (X*):

Formula (X*) wherein: r is independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety. 46. A compound of Formula (Xa*): Formula (Xa*) 47. A compound of Formula (Xb*):

Formula (Xb*) 48. A compound of Formula (XI*):

Formula (XI*) wherein: s is independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety. 49. A compound of Formula (XIa*):

Formula (XIa*) 50. A compound of Formula (XIb*):

Formula (XIb*) 51. Use of a compound according to any of Clauses 45 and 48 to 50, for the preparation of a compound according to any of Clauses 1 to 40. 52. Use of a compound according to Clause 46, for the preparation of a compound according to any of Clauses 6, 8 to 14, 16 to 33, and 35 to 40. 53. Use of a compound according to Clause 47, for the preparation of a compound according to any of Clauses 5, 7, 9 to 13, 15 to 32, and 34 to 40. 54. A compound or composition obtained, or obtainable by a process according to any of Clauses 41 to 44. 55. A pharmaceutical composition comprising of a compound according to any of Clauses 1 to 40, together with a pharmaceutically acceptable carrier, diluent or excipient. A compound according to any of Clauses 1 to 40, for use in therapy. EXAMPLES The invention will be more fully understood by reference to the following examples. They should not, however, be construed as limiting the scope of the invention. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. Example 1 – Target identification Background All biological functions arise from the co-ordinated interaction of hundreds of interacting molecules – primarily proteins – and can be thought of as the emergent functional consequence of protein-protein interaction networks where each node in the network is a protein and each edge linking the proteins can represent a range of possible interaction types from complex formation to catalytic activation etc. Historically such functions have been represented as simplistic linear pathways. As knowledge has grown however, it has become clear that pathways are more complex and that the minimum level of complexity that adequately represents the functional properties of a biological process, and can capture the characteristics of resilience to perturbation and robustness to random damage of individual components, is a network. Networks subserving biological function may consist of several interacting canonical pathways as well as additional proteins that are primarily engaged when the canonical function is perturbed. It is therefore critical to develop approaches that can model this complexity in a meaningful and tractable way; and generate target hypotheses that take account of the inherent resistance to change that is a consequence of network robustness. Oversimplification of biology and the failure to make rational drug target choices based on realistic models of biological processes has contributed to the poor success rate of drug discovery. Furthermore, there has been a lack of rigorous objective methods both for making network models of processes and for prioritising protein targets within these models. As a consequence target selection decisions are frequently made on an ad hoc basis based on preference or evidence unrelated to the functional model. Process for identifying processes and targets The starting point for the identification of the target SLC25A5/ANT2 was HepNet, a proprietary computational platform for the identification and validation of drug targets in hepatocytes. Two independent approaches were used for the identification of SLC25A5/ANT2, the first utilised omics data in the form of Genome Wide Association Studies (GWAS) metanalyses to identify targets for Non-Alcoholic Fatty Liver Disease (NAFLD) from experimental data. The second approach utilised the HepNet knowledge graph, a semantic network describing interactions between entities such as genes, drugs, diseases and/or biological processes in the context of hepatocytes. For the GWAS-based approach metanalyses were QC'ed for sample size, target population, and quality of statistical analysis. More specifically, a sample size of more than 1,000 was used as a cut-off, SNPs were taken forward if the p-value was reflecting multiple testing corrections. Finally, sex- combined and all-ancestries SNPs were selected (continental European, UK, other); SNPs with gender-specific significance were excluded. The resulting selected GWAS were used to extract the SNPs with strong association with the trait of interest, in this case NAFLD pathophysiology as well as associated metabolic dysfunction (for example, NAFLD and cardiometabolic diseases or steatosis and risk of NAFLD). As a subsequent step, the SNPs were mapped to genes using the Variant-to-Gene (V2G) pipeline data from Open Targets Genetics (https://genetics.opentargets.org/). More specifically, for each SNP of interest the gene with the highest score (or genes, in case of a top-score tie) based on the V2G pipeline were selected, along with those genes with a score above 0.2. This generated a set of genes that could be used as an input for building protein-protein interaction networks, using a proprietary algorithm (algorithm A). Impact analysis (algorithm B) was then performed on the resulting networks to identify the biological processes enriched in the networks. These processes were then manually assessed by an internal team to identify the most relevant biological processes for NAFLD target identification. Protein-protein interaction networks were then built around the selected processes and the nodes scored for their importance to the network using a proprietary algorithm (algorithm C). The highest scoring nodes from algorithm C were manually assessed by an internal team to identify targets of interest for the treatment of NAFLD metabolic diseases. For the knowledge graph-based approach machine learning algorithms were used to predict interactions between genes and disease based upon the structure of the knowledge graph, a task commonly referred to as ‘link prediction’. This generated a set of genes that could be used for network-based target identification using proprietary algorithms A-C as described above. The networks and other outputs from these algorithms were different from the ones generated by the GWAS-based analysis and were assessed by a different internal team. Both analyses independently identified ANT2/SLC25A5 as being an important node in a biological process involved in "Adipogenesis/Non-alcoholic fatty liver disease" (termed Supercluster 574 in algorithm B). The inventors have thus analysed these network models using proprietary analytical methods. These methods use directional information to capture key ‘target’ properties such as whether a protein is an integrator of information, a key conduit of information to other parts of the network, an influencer of key proteins and the extent to which an influencer is influenced or influences other proteins (based on absolute and relative number and direction of inputs and outputs). The directional information also enables hierarchical relationships between proteins to be imputed. Proteins higher in the hierarchy and with certain properties may be preferred over others with otherwise similar properties. The relative specificity and magnitude of each property relative to the others made it possible for the inventors to score and rank proteins in terms of their target suitability. The ability to characterise the properties of these targets in terms of network relationships enables judgements to be made on the selectivity and magnitude of effect in the chosen context and hence the suitability of each for a given indication. Proprietary analytical techniques were then applied to the network models to identify pharmacologically viable targets from within the networks whose knockdown will have a significant influence on the network and by extension on the biological function being modelled. The algorithms make extensive use of directional information and hierarchical relationships to identify targets with a range of specific properties that will make them good siRNA targets. Targets were then further filtered by protein class and hepatocyte specific properties according to the therapeutic requirements. The above workflow leveraging proprietary data resources and network node metrics has identified the provided target for the provided uses. The outcome of the network approach is shown in Table 6. ANT2 was surprisingly identified as a drug target for NAFLD among various other targets that have been previously associated with metabolic disorders, such NAFLD (APOA5, HMDH, APOC3, NR1H3, MTP, PCSK9, SOAT1 and ABCA1). Table 6 Protein name Accession number Prediction score for Hepatocellular NAFLD expression rank APOA5 Q6Q788 93.6 0.46 HMDH P04035 91.3 0.54 APOC3 P02656 91.2 0.95 NR1H3 Q13133 91.1 0.22 MTP P55157 88.1 0.96 ANT2 P05141 80 0.98 PCSK9 Q8NBP7 79.3 0.21 SOAT1 P35610 77.7 0.27 ABCA1 O095477 77.0 0.46 Example 2: Synthesis of tether 1 General Experimental conditions: Thin layer chromatography (TLC) was performed on silica-coated aluminium plates with fluorescence indicator 254 nm from Macherey-Nagel. Compounds were visualized under UV light (254 nm), or after spraying with the 5% H₂SO₄ in methanol (MeOH) or ninhydrin reagent according to Stahl (from Sigma-Aldrich), followed by heating. Flash chromatography was performed with a Biotage Isolera One flash chromatography instrument equipped with a dual variable UV wavelength detector (200-400 nm) using Biotage Sfär Silica 10, 25, 50 or 100 g columns (Uppsala, Sweden). All moisture-sensitive reactions were carried out under anhydrous conditions using dry glassware, anhydrous solvents, and argon atmosphere. All commercially available reagents were purchased from Sigma-Aldrich and solvents from Carl Roth GmbH + Co. KG. D-Galactosamine pentaacetate was purchased from AK scientific. HPLC/ESI-MS was performed on a Dionex UltiMate 3000 RS UHPLC system and Thermo Scientific MSQ Plus Mass spectrometer using an Acquity UPLC Protein BEH C4 column from Waters (300Å, 1.7 µm, 2.1 x 100 mm) at 60 °C. The solvent system consisted of solvent A with H2O containing 0.1% formic acid and solvent B with acetonitrile (ACN) containing 0.1% formic acid. A gradient from 5-100% of B over 15 min with a flow rate of 0.4 mL/min was employed. Detector and conditions: Corona ultra-charged aerosol detection (from esa). Nebulizer Temp.: 25 °C. N2 pressure: 35.1 psi. Filter: Corona. ₁H and ₁₃C NMR spectra were recorded at room temperature on a Varian spectrometer at 500 MHz (₁H NMR) and 125 MHz (₁₃C NMR). Chemical shifts are given in ppm referenced to the solvent residual peak (CDCl3 – 1H NMR: δ at 7.26 ppm and 13C NMR δ at 77.2 ppm; DMSO-d6 – ₁H NMR: δ at 2.50 ppm and ₁₃C NMR δ at 39.5 ppm). Coupling constants are given in Hertz. Signal splitting patterns are described as singlet (s), doublet (d), triplet (t) or multiplet (m). Synthesis route for the conjugate building block TriGalNAc _Tether1: Preparation of compound 2: D-Galactosamine pentaacetate (3.00 g, 7.71 mmol, 1.0 eq.) was dissolved in anhydrous dichloromethane (DCM) (30 mL) under argon and trimethylsilyl trifluoromethanesulfonate (TMSOTf, 4.28 g, 19.27 mmol, 2.5 eq.) was added. The reaction was stirred at room temperature for 3 h. The reaction mixture was diluted with DCM (50 mL) and washed with cold saturated aq. NaHCO₃ (100 mL) and water (100 mL). The organic layer was separated, dried over Na2SO4 and concentrated to afford the title compound as yellow oil, which was purified by flash chromatography (gradient elution: 0-10% MeOH in DCM in 10 CV). The product was obtained as colourless oil (2.5 g, 98%, rf= 0.45 (2% MeOH in DCM)). Preparation of compound 4: Compound 2 (2.30 g, 6.98 mmol, 1.0 eq.) and azido-PEG3-OH (1.83 g, 10.5 mmol, 1.5 eq.) were dissolved in anhydrous DCM (40 mL) under argon and molecular sieves 3 Å (5 g) were added to the solution. The mixture was stirred at room temperature for 1 h. TMSOTf (0.77 g, 3.49 mmol, 0.5 eq.) was then added to the mixture and the reaction was stirred overnight. The molecular sieves were filtered, the filtrate was diluted with DCM (100 mL) and washed with cold saturated aq. NaHCO₃ (100 mL) and water (100 mL). The organic layer was separated, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography (gradient elution: 0-3% MeOH in DCM in 10 CV) to afford the title product as light yellow oil (3.10 g, 88%, rf = 0.25 (2% MeOH in DCM)). MS: calculated for C₂₀H₃₂N₄O₁₁, 504.21. Found 505.4.1H NMR (500 MHz, CDCl3) ^ 6.21-6.14 (m, 1H), 5.30 (dd, J = 3.4, 1.1 Hz, 1H), 5.04 (dd, J = 11.2, 3.4 Hz,1H), 4.76 (d, J = 8.6 Hz, 1H), 4.23-4.08 (m, 3H), 3.91-3.80 (m, 3H), 3.74-3.59 (m, 9H), 3.49- 3.41 (m, 2H), 2.14 (s, 3H), 2.02 (s, 3H), 1.97 (d, J = 4.2 Hz, 6H).13C NMR (125 MHz, CDCl3) ^ 170.6 (C), 170.5 (C), 170.4 (C), 170.3 (C), 102.1 (CH), 71.6 (CH), 70.8 (CH), 70.6 (CH), 70.5 (CH), 70.3 (CH2), 69.7 (CH2), 68.5 (CH2), 66.6 (CH2), 61.5 (CH2), 23.1 (CH3), 20.7 (3xCH3). Preparation of compound 5: Compound 4 (1.00 g, 1.98 mmol, 1.0 eq.) was dissolved in a mixture of ethyl acetate (EtOAc) and MeOH (30 mL 1:1 v/v) and Pd/C (100 mg) was added. The reaction mixture was degassed using vacuum/argon cycles (3x) and hydrogenated under balloon pressure overnight. The reaction mixture was filtered through celite and washed with EtOAc (30 mL). The solvent was removed under reduced pressure to afford the title compound as colourless oil (0.95 g, quantitative yield, rf = 0.25 (10% MeOH in DCM)). The compound was used without further purification. MS: calculated for C20H34N2O11, 478.2. Found 479.4. Preparation of compound 7: Tris{[2-(tert-butoxycarbonyl)ethoxy]methyl}-methylamine 6 (3.37 g, 6.67 mmol, 1.0 eq.) was dissolved in a mixture of DCM/water (40 mL 1:1 v/v) and Na₂CO₃ (0.18 g, 1.7 mmol, 0.25 eq.) was added while stirring vigorously. Benzyl chloroformate (2.94 mL, 20.7 mmol, 3.10 eq.) was added dropwise to the previous mixture and the reaction was stirred at room temperature for 24 h. The reaction mixture was diluted with CH2Cl2 (100 mL) and washed with water (100 mL). The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the resulting crude material was purified by flash chromatography (gradient elution: 0-10% EtOAc in cyclohexane in 12 CV) to afford the title compound as pale yellowish oil (3.9 g, 91%, rf = 0.56 (10% EtOAc in cyclohexane)). MS: calculated for C₃₃H₅₃NO₁₁, 639.3. Found 640.9.1H NMR (500 MHz, DMSO-d6) ^ 7.38-7.26 (m, 5H), 4.97 (s, 2H), 3.54 (t, 6H), 3.50 (s, 6H), 2.38 (t, 6H), 1.39 (s, 27H).13C NMR (125 MHz, DMSO-d6) ^ 170.3 (3xC), 154.5 (C), 137.1 (C), 128.2 (2xCH), 127.7 (CH), 127.6 (2xCH), 79.7 (3xC), 68.4 (3xCH2), 66.8 (3xCH2), 64.9 (C), 58.7 (CH2), 35.8 (3xCH2), 27.7 (9xCH3). Preparation of compound 8: Cbz-NH-tris-Boc-ester 7 (0.20 g, 0.39 mmol, 1.0 eq.) was dissolved in CH2Cl2 (1 mL) under argon, trifluoroacetic acid (TFA, 1 mL) was added and the reaction was stirred at room temperature for 1 h. The solvent was removed under reduced pressure, the residue was co-evaporated 3 times with toluene (5 mL) and dried under high vacuum to get the compound as its TFA salt (0.183 g, 98%). The compound was used without further purification. MS: calculated for C21H29NO11, 471.6. Found 472.4. Preparation of compound 9: CbzNH-tris-COOH 8 (0.72 g, 1.49 mmol, 1.0 eq.) and GalNAc- PEG3-NH₂5 (3.56 g, 7.44 mmol, 5.0 eq.) were dissolved in N,N-dimethylformamide (DMF) (25 mL). Then N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (2.78 g, 7.44 mmol, 5.0 eq.), 1-hydroxybenzotriazole hydrate (HOBt) (1.05 g, 7.44 mmol, 5.0 eq.) and N,N-diisopropylethylamine (DIPEA) (2.07 mL, 11.9 mmol, 8.0 eq.) were added to the solution and the reaction was stirred for 72 h. The solvent was removed under reduced pressure, the residue was dissolved in DCM (100 mL) and washed with saturated aq. NaHCO3 (100 mL). The organic layer was dried over Na2SO4, the solvent evaporated and the crude material was purified by flash chromatography (gradient elution: 0-5% MeOH in DCM in 14 CV). The product was obtained as pale yellowish oil (1.2 g, 43%, rf = 0.20 (5% MeOH in DCM)). MS: calculated for C81H125N7O41, 1852.9. Found 1854.7.1H NMR (500 MHz, DMSO- d6) ^ 7.90-7.80 (m, 10H), 7.65-7.62 (m, 4H), 7.47-7.43 (m, 3H), 7.38-7.32 (m, 8H), 5.24-5.22 (m, 3H), 5.02-4.97 (m, 4H), 4.60-4.57 (m, 3 H), 4.07-3.90 (m 10H), 3.67-3.36 (m, 70H), 3.23- 3.07 (m, 25H), 2.18 (s, 10H), 2.00 (s, 13H), 1.89 (s, 11H), 1.80-1.78 (m, 17H).13C NMR (125 MHz, DMSO-d6) ^ 170.1 (C), 169.8 (C), 169.7 (C), 169.4 (C), 169.2 (C), 169.1 (C), 142.7 (C), 126.3 (CH), 123.9 (CH), 118.7 (CH), 109.7 (CH), 100.8 (CH), 70.5 (CH), 69.8 (CH), 69.6 (CH), 69.5 (CH), 69.3 (CH2), 69.0 (CH2), 68.2 (CH2), 67.2 (CH2), 66.7 (CH2), 61.4 (CH2), 22.6 (CH2), 22.4 (3xCH3), 20.7 (9xCH3). O O O O O O O O O O O O O ^O NH O O O O HN O O O NH HN ^O O _O ^O O O O O O O O O Pd/C, H O O O O O O O _O O NH ^O N O O MeOH,drops o O O O O O H N Cbz f AcOH H _O N O O ^O O NH O O H NH O O O O O O O O O O N O O O HN ^O H O O O N O HN ^O H O 9 O ¹⁰ Preparation of compound 10: Triantennary GalNAc compound 9 (0.27 g, 0.14 mmol, 1.0 eq.) was dissolved in MeOH (15 mL), 3 drops of acetic acid (AcOH) and Pd/C (30 mg) was added. The reaction mixture was degassed using vacuum/argon cycles (3x) and hydrogenated under balloon pressure overnight. The completion of the reaction was followed by mass spectrometry and the resulting mixture was filtered through a thin pad of celite. The solvent was evaporated and the residue obtained was dried under high vacuum and used for the next step without further purification. The product was obtained as pale yellowish oil (0.24 g, quantitative yield). MS: calculated for C₇₃H₁₁₉N₇O₃₉, 1718.8. Found 1719.3.

Preparation of compound 11: Commercially available suberic acid bis(N-hydroxysuccinimide ester) (3.67 g, 9.9 mmol, 1.0 eq.) was dissolved in DMF (5 mL) and triethylamine (1.2 mL) was added. To this solution was added dropwise a solution of 3-azido-1-propylamine (1.0 g, 9.9 mmol, 1.0 eq.) in DMF (5 mL). The reaction was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc (100 mL) and washed with water (50 mL). The organic layer was separated, dried over Na₂SO₄ and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography (gradient elution: 0-5% MeOH in DCM in 16 CV). The product was obtained as white solid (1.54 g, 43%, rf = 0.71 (5% MeOH in DCM)). MS: calculated for C15H23N5O5, 353.4. Found 354.3. O ^O O O O O O O O O O O O NH O O O O O ^O HN ^O _O NH HN ^O O O O O O O O O O O O O O O O O O _O O N O O O O O O NH ^O O ^O H H _O N O O N O NH ^O CH C H NH O l , Et N O O O N N H O O O O O O O O O O O O O HN ^O N O O H _O ^O N O HN H O 10 O + 12 O O O N N N O H O 11 Preparation of TriGalNAc (12): Triantennary GalNAc compound 10 (0.35 g, 0.24 mmol, 1.0 eq.) and compound 11 (0.11 g, 0.31 mmol, 1.5 eq.) were dissolved in DCM (5 mL) under argon and triethylamine (0.1 mL, 0.61 mmol, 3.0 eq.) was added. The reaction was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was dissolved in EtOAc (100 mL) and washed with water (100 mL). The organic layer was separated and dried over Na2SO4. The solvent was evaporated and the resulting crude material was purified by flash chromatography (elution gradient: 0-10% MeOH in DCM in 20 CV) to afford the title compound as white fluffy solid (0.27 g, 67%, rf = 0.5 (10% MeOH in DCM)). MS: calculated for C84H137N11O41, 1957.1. Found 1959.6. Conjugation of Tether 1 to a siRNA strand: Monofluoro cyclooctyne (MFCO) conjugation at 5’- or 3’-end 5‘-end MFCO conjugation

3‘-end MFCO conjugation

General conditions for MFCO conjugation: Amine-modified single strand was dissolved at 700 OD/mL in 50 mM carbonate/bicarbonate buffer pH 9.6/dimethyl sulfoxide (DMSO) 4:6 (v/v) and to this solution was added one molar equivalent of a 35 mM solution of MFCO-C6-NHS ester (Berry&Associates, Cat. # LK 4300) in DMF. The reaction was carried out at room temperature and after 1 h another molar equivalent of the MFCO solution was added. The reaction was allowed to proceed for an additional hour and was monitored by LC/MS. At least two molar equivalent excess of the MFCO NHS ester reagent relative to the amino modified oligonucleotide were needed to achieve quantitative consumption of the starting material. The reaction mixture was diluted 15-fold with water, filtered through a 1.2 µm filter from Sartorius and then purified by reserve phase (RP HPLC) on an Äkta Pure instrument (GE Healthcare). Purification was performed using a XBridge C18 Prep 19 x 50 mm column from Waters. Buffer A was 100 mM TEAAc pH 7 and buffer B contained 95% acetonitrile in buffer A. A flow rate of 10 mL/min and a temperature of 60°C were employed. UV traces at 280 nm were recorded. A gradient of 0-100% B within 60 column volumes was employed. Fractions containing full length conjugated oligonucleotide were pooled, precipitated in the freezer with 3 M NaOAc, pH 5.2 and 85% ethanol and the collected pellet was dissolved in water. Samples were desalted by size exclusion chromatography and concentrated using a speed-vac concentrator to yield the conjugated oligonucleotide in an isolated yield of 40–80%. 5’-GalNAc-T1 conjugates

3’-GalNAc-T1 conjugates

General procedure for TriGalNAc conjugation: MFCO-modified single strand was dissolved at 2000 OD/mL in water and to this solution was added one equivalent solution of compound 12 (10 mM) in DMF. The reaction was carried out at room temperature and after 3 h 0.7 molar equivalent of the compound 12 solution was added. The reaction was allowed to proceed overnight and completion was monitored by LCMS. The conjugate was diluted 15-fold in water, filtered through a 1.2 µm filter from Sartorius and then purified by RP HPLC on an Äkta Pure instrument (GE Healthcare). RP HPLC purification was performed using a XBridge C18 Prep 19 x 50 mm column from Waters. Buffer A was 100 mM triethylammonium acetate pH 7 and buffer B contained 95% acetonitrile in buffer A. A flow rate of 10 mL/min and a temperature of 60°C were employed. UV traces at 280 nm were recorded. A gradient of 0-100% B within 60 column volumes was employed. Fractions containing full-length conjugated oligonucleotide were pooled, precipitated in the freezer with 3 M NaOAc, pH 5.2 and 85% ethanol and the collected pellet was dissolved in water to give an oligonucleotide solution of about 1000 OD/mL. The O-acetates were removed by adding 20% aqueous ammonia. Quantitative removal of these protecting groups was verified by LC-MS. The conjugates were desalted by size exclusion chromatography using Sephadex G25 Fine resin (GE Healthcare) on an Äkta Pure (GE Healthcare) instrument to yield the conjugated oligonucleotides in an isolated yield of 50–70%. The following schemes further set out the routes of synthesis: Scheme 1:

Scheme 2:

Scheme 3:

Scheme 4:

Scheme 5:

Example 3: Duplex Annealing To generate the desired siRNA duplex, the two complementary strands were annealed by combining equimolar aqueous solutions of both strands. The mixtures were placed into a water bath at 70°C for 5 minutes and subsequently allowed to cool to ambient temperature within 2 h. The duplexes were lyophilized for 2 days and stored at -20°C. The duplexes were analyzed by analytical SEC HPLC on Superdex™ 75 Increase 5/150 GL column 5 x 153-158 mm (Cytiva) on a Dionex Ultimate 3000 (Thermo Fisher Scientific) HPLC system. Mobile phase consisted of 1x PBS containing 10% acetonitrile. An isocratic gradient was run in 10 min at a flow rate of 1.5 mL/min at room temperature. UV traces at 260 and 280 nm were recorded. Water (LC-MS grade) was purchased from Sigma-Aldrich and Phosphate- buffered saline (PBS; 10x, pH 7.4) was purchased from GIBCO (Thermo Fisher Scientific). Example 4: Synthesis of tether 2 General Experimental conditions: Thin layer chromatography (TLC) was performed on silica-coated aluminium plates with fluorescence indicator 254 nm from Macherey-Nagel. Compounds were visualized under UV light (254 nm), or after spraying with the 5% H₂SO₄ in methanol (MeOH) or ninhydrin reagent according to Stahl (from Sigma-Aldrich), followed by heating. Flash chromatography was performed with a Biotage Isolera One flash chromatography instrument equipped with a dual variable UV wavelength detector (200-400 nm) using Biotage Sfär Silica 10, 25, 50 or 100 g columns (Uppsala, Sweden). All moisture-sensitive reactions were carried out under anhydrous conditions using dry glassware, anhydrous solvents, and argon atmosphere. All commercially available reagents were purchased from Sigma-Aldrich and solvents from Carl Roth GmbH + Co. KG. D-Galactosamine pentaacetate was purchased from AK scientific. HPLC/ESI-MS was performed on a Dionex UltiMate 3000 RS UHPLC system and Thermo Scientific MSQ Plus Mass spectrometer using an Acquity UPLC Protein BEH C4 column from Waters (300Å, 1.7 µm, 2.1 x 100 mm) at 60 °C. The solvent system consisted of solvent A with H2O containing 0.1% formic acid and solvent B with acetonitrile (ACN) containing 0.1% formic acid. A gradient from 5-100% of B over 15 min with a flow rate of 0.4 mL/min was employed. Detector and conditions: Corona ultra-charged aerosol detection (from esa). Nebulizer Temp.: 25 °C. N2 pressure: 35.1 psi. Filter: Corona. 1H and 13C NMR spectra were recorded at room temperature on a Varian spectrometer at 500 MHz (1H NMR) and 125 MHz (13C NMR). Chemical shifts are given in ppm referenced to the solvent residual peak (CDCl₃ – ₁H NMR: δ at 7.26 ppm and ₁₃C NMR δ at 77.2 ppm; DMSO-d6 – ₁H NMR: δ at 2.50 ppm and ₁₃C NMR δ at 39.5 ppm). Coupling constants are given in Hertz. Signal splitting patterns are described as singlet (s), doublet (d), triplet (t) or multiplet (m). Synthesis route for the conjugate building block TriGalNAc _Tether2: Preparation of compound 2: D-Galactosamine pentaacetate (3.00 g, 7.71 mmol, 1.0 eq.) was dissolved in anhydrous dichloromethane (DCM) (30 mL) under argon and trimethylsilyl trifluoromethanesulfonate (TMSOTf, 4.28 g, 19.27 mmol, 2.5 eq.) was added. The reaction was stirred at room temperature for 3 h. The reaction mixture was diluted with DCM (50 mL) and washed with cold saturated aq. NaHCO3 (100 mL) and water (100 mL). The organic layer was separated, dried over Na₂SO₄, and concentrated to afford the title compound as yellow oil, which was purified by flash chromatography (gradient elution: 0-10% MeOH in DCM in 10 CV). The product was obtained as colourless oil (2.5 g, 98%, rf= 0.45 (2% MeOH in DCM)). Preparation of compound 4: Compound 2 (2.30 g, 6.98 mmol, 1.0 eq.) and azido-PEG3-OH (1.83 g, 10.5 mmol, 1.5 eq.) were dissolved in anhydrous DCM (40 mL) under argon and molecular sieves 3 Å (5 g) were added to the solution. The mixture was stirred at room temperature for 1 h. TMSOTf (0.77 g, 3.49 mmol, 0.5 eq.) was then added to the mixture and the reaction was stirred overnight. The molecular sieves were filtered, the filtrate was diluted with DCM (100 mL) and washed with cold saturated aq. NaHCO3 (100 mL) and water (100 mL). The organic layer was separated, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography (gradient elution: 0-3% MeOH in DCM in 10 CV) to afford the title product as light-yellow oil (3.10 g, 88%, rf = 0.25 (2% MeOH in DCM)). MS: calculated for C20H32N4O11, 504.21. Found 505.4.1H NMR (500 MHz, CDCl3) ^ 6.21-6.14 (m, 1H), 5.30 (dd, J = 3.4, 1.1 Hz, 1H), 5.04 (dd, J = 11.2, 3.4 Hz,1H), 4.76 (d, J = 8.6 Hz, 1H), 4.23-4.08 (m, 3H), 3.91-3.80 (m, 3H), 3.74-3.59 (m, 9H), 3.49- 3.41 (m, 2H), 2.14 (s, 3H), 2.02 (s, 3H), 1.97 (d, J = 4.2 Hz, 6H).13C NMR (125 MHz, CDCl3) ^ 170.6 (C), 170.5 (C), 170.4 (C), 170.3 (C), 102.1 (CH), 71.6 (CH), 70.8 (CH), 70.6 (CH), 70.5 (CH), 70.3 (CH2), 69.7 (CH2), 68.5 (CH2), 66.6 (CH2), 61.5 (CH2), 23.1 (CH3), 20.7 (3xCH3). Preparation of compound 5: Compound 4 (1.00 g, 1.98 mmol, 1.0 eq.) was dissolved in a mixture of ethyl acetate (EtOAc) and MeOH (30 mL 1:1 v/v) and Pd/C (100 mg) was added. The reaction mixture was degassed using vacuum/argon cycles (3x) and hydrogenated under balloon pressure overnight. The reaction mixture was filtered through celite and washed with EtOAc (30 mL). The solvent was removed under reduced pressure to afford the title compound as colourless oil (0.95 g, quantitative yield, rf = 0.25 (10% MeOH in DCM)). The compound was used without further purification. MS: calculated for C₂₀H₃₄N₂O₁₁, 478.2. Found 479.4. Preparation of compound 7: Tris{[2-(tert-butoxycarbonyl)ethoxy]methyl}-methylamine 6 (3.37 g, 6.67 mmol, 1.0 eq.) was dissolved in a mixture of DCM/water (40 mL 1:1 v/v) and Na2CO3 (0.18 g, 1.7 mmol, 0.25 eq.) was added while stirring vigorously. Benzyl chloroformate (2.94 mL, 20.7 mmol, 3.10 eq.) was added dropwise to the previous mixture and the reaction was stirred at room temperature for 24 h. The reaction mixture was diluted with CH2Cl2 (100 mL) and washed with water (100 mL). The organic layer was separated and dried over Na2SO4. The solvent was removed under reduced pressure and the resulting crude material was purified by flash chromatography (gradient elution: 0-10% EtOAc in cyclohexane in 12 CV) to afford the title compound as pale yellowish oil (3.9 g, 91%, rf = 0.56 (10% EtOAc in cyclohexane)). MS: calculated for C33H53NO11, 639.3. Found 640.9.1H NMR (500 MHz, DMSO-d6) ^ 7.38-7.26 (m, 5H), 4.97 (s, 2H), 3.54 (t, 6H), 3.50 (s, 6H), 2.38 (t, 6H), 1.39 (s, 27H).13C NMR (125 MHz, DMSO-d6) ^ 170.3 (3xC), 154.5 (C), 137.1 (C), 128.2 (2xCH), 127.7 (CH), 127.6 (2xCH), 79.7 (3xC), 68.4 (3xCH2), 66.8 (3xCH2), 64.9 (C), 58.7 (CH2), 35.8 (3xCH2), 27.7 (9xCH3). Preparation of compound 8: Cbz-NH-tris-Boc-ester 7 (0.20 g, 0.39 mmol, 1.0 eq.) was dissolved in CH₂Cl₂ (1 mL) under argon, trifluoroacetic acid (TFA, 1 mL) was added and the reaction was stirred at room temperature for 1 h. The solvent was removed under reduced pressure, the residue was co-evaporated 3 times with toluene (5 mL) and dried under high vacuum to get the compound as its TFA salt (0.183 g, 98%). The compound was used without further purification. MS: calculated for C₂₁H₂₉NO₁₁, 471.6. Found 472.4. Preparation of compound 9: CbzNH-tris-COOH 8 (0.72 g, 1.49 mmol, 1.0 eq.) and GalNAc- PEG3-NH25 (3.56 g, 7.44 mmol, 5.0 eq.) were dissolved in N,N-dimethylformamide (DMF) (25 mL). Then N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) (2.78 g, 7.44 mmol, 5.0 eq.), 1-hydroxybenzotriazole hydrate (HOBt) (1.05 g, 7.44 mmol, 5.0 eq.) and N,N-diisopropylethylamine (DIPEA) (2.07 mL, 11.9 mmol, 8.0 eq.) were added to the solution and the reaction was stirred for 72 h. The solvent was removed under reduced pressure, the residue was dissolved in DCM (100 mL) and washed with saturated aq. NaHCO3 (100 mL). The organic layer was dried over Na₂SO₄, the solvent evaporated and the crude material was purified by flash chromatography (gradient elution: 0-5% MeOH in DCM in 14 CV). The product was obtained as pale yellowish oil (1.2 g, 43%, rf = 0.20 (5% MeOH in DCM)). MS: calculated for C₈₁H₁₂₅N₇O₄₁, 1852.9. Found 1854.7.1H NMR (500 MHz, DMSO- d6) ^ 7.90-7.80 (m, 10H), 7.65-7.62 (m, 4H), 7.47-7.43 (m, 3H), 7.38-7.32 (m, 8H), 5.24-5.22 (m, 3H), 5.02-4.97 (m, 4H), 4.60-4.57 (m, 3 H), 4.07-3.90 (m 10H), 3.67-3.36 (m, 70H), 3.23- 3.07 (m, 25H), 2.18 (s, 10H), 2.00 (s, 13H), 1.89 (s, 11H), 1.80-1.78 (m, 17H).13C NMR (125 MHz, DMSO-d6) ^ 170.1 (C), 169.8 (C), 169.7 (C), 169.4 (C), 169.2 (C), 169.1 (C), 142.7 (C), 126.3 (CH), 123.9 (CH), 118.7 (CH), 109.7 (CH), 100.8 (CH), 70.5 (CH), 69.8 (CH), 69.6 (CH), 69.5 (CH), 69.3 (CH2), 69.0 (CH2), 68.2 (CH2), 67.2 (CH2), 66.7 (CH2), 61.4 (CH2), 22.6 (CH2), 22.4 (3xCH3), 20.7 (9xCH3). Preparation of compound 10: Triantennary GalNAc compound 9 (0.27 g, 0.14 mmol, 1.0 eq.) was dissolved in MeOH (15 mL), 3 drops of acetic acid (AcOH) and Pd/C (30 mg) was added. The reaction mixture was degassed using vacuum/argon cycles (3x) and hydrogenated under balloon pressure overnight. The completion of the reaction was followed by mass spectrometry and the resulting mixture was filtered through a thin pad of celite. The solvent was evaporated, and the residue obtained was dried under high vacuum and used for the next step without further purification. The product was obtained as pale yellowish oil (0.24 g, quantitative yield). MS: calculated for C₇₃H₁₁₉N₇O₃₉, 1718.8. Found 1719.3.

Preparation of compound 14: Triantennary GalNAc compound 10 (0.45 g, 0.26 mmol, 1.0 eq.), HBTU (0.19 g, 0.53 mmol, 2.0 eq.) and DIPEA (0.23 mL, 1.3 mmol, 5.0 eq.) were dissolved in DCM (10 mL) under argon. To this mixture, it was added dropwise a solution of compound 13 (0.14 g, 0.53 mmol, 2.0 eq.) in DCM (5 mL). The reaction was stirred at room temperature overnight. The solvent was removed, and the residue was dissolved in EtOAc (50 mL), washed with water (50 mL) and dried over Na2SO4. The solvent was evaporated, and the crude material was purified by flash chromatography (gradient elution: 0-5% MeOH in DCM in 20 CV). The product was obtained as white fluffy solid (0.25 g, 48%, rf = 0.4 (10% MeOH in DCM)). MS: calculated for C88H137N7O42, 1965.1. Found 1965.6.

Preparation of TriGalNAc (15): Triantennary GalNAc compound 14 (0.31 g, 0.15 mmol, 1.0 eq.) was dissolved in EtOAc (15 mL) and Pd/C (40 mg) was added. The reaction mixture was degassed by using vacuum/argon cycles (3x) and hydrogenated under balloon pressure overnight. The completion of the reaction was monitored by mass spectrometry and the resulting mixture was filtered through a thin pad of celite. The solvent was removed under reduced pressure and the resulting residue was dried under high vacuum overnight. The residue was used for conjugations to oligonucleosides without further purification (0.28 g, quantitative yield). MS: calculated for C81H131N7O42, 1874.9. Found 1875.3. Conjugation of Tether 2 to a siRNA strand: TriGalNAc tether 2 (GalNAc-T2) conjugation at 5’- end or 3’-end 5’-GalNAc-T2 conjugates

3’-GalNAc-T2 conjugates

Preparation of TriGalNAc tether 2 NHS ester: To a solution of carboxylic acid tether 2 (compound 15, 227 mg, 121 µmol) in DMF (2.1 mL), N-hydroxysuccinimide (NHS) (15.3 mg, 133 µmol) and N,N′-diisopropylcarbodiimide (DIC) (19.7 µL, 127 µmol) were added. The solution was stirred at room temperature for 18 h and used without purification for the subsequent conjugation reactions. General procedure for triGalNAc tether 2 conjugation: Amine-modified single strand was dissolved at 700 OD/mL in 50 mM carbonate/bicarbonate buffer pH 9.6/DMSO 4:6 (v/v) and to this solution was added one molar equivalent of Tether 2 NHS ester (57 mM) solution in DMF. The reaction was carried out at room temperature and after 1 h another molar equivalent of the NHS ester solution was added. The reaction was allowed to proceed for one more hour and reaction progress was monitored by LCMS. At least two molar equivalent excess of the NHS ester reagent relative to the amino modified oligonucleoside were needed to achieve quantitative consumption of the starting material. The reaction mixture was diluted 15-fold with water, filtered once through 1.2 µm filter from Sartorius and then purified by reserve phase (RP HPLC) on an Äkta Pure (GE Healthcare) instrument. The purification was performed using a XBridge C18 Prep 19 x 50 mm column from Waters. Buffer A was 100 mM TEAA pH 7 and buffer B contained 95% acetonitrile in buffer A. A flow rate of 10 mL/min and a temperature of 60°C were employed. UV traces at 280 nm were recorded. A gradient of 0–100% B within 60 column volumes was employed. Fractions containing full-length conjugated oligonucleosides were pooled together, precipitated in the freezer with 3 M NaOAc, pH 5.2 and 85% ethanol and then dissolved at 1000 OD/mL in water. The O-acetates were removed with 20% ammonium hydroxide in water until completion (monitored by LC-MS). The conjugates were desalted by size exclusion chromatography using Sephadex G25 Fine resin (GE Healthcare) on an Äkta Pure (GE Healthcare) instrument to yield the conjugated oligonucleotides in an isolated yield of 60–80%. The conjugates were characterized by HPLC–MS analysis with a 2.1 x 50 mm XBridge C18 column (Waters) on a Dionex Ultimate 3000 (Thermo Fisher Scientific) HPLC system equipped with a Compact ESI-Qq-TOF mass spectrometer (Bruker Daltonics). Buffer A was 16.3 mM triethylamine, 100 mM HFIP in 1% MeOH in H2O and buffer B contained 95% MeOH in buffer A. A flow rate of 250 µL/min and a temperature of 60°C were employed. UV traces at 260 and 280 nm were recorded. A gradient of 1-100% B within 31 min was employed. The following schemes further set out the routes of synthesis:

Scheme 6:

Scheme 7:

Scheme 8:

Scheme 9:

Example 5: Duplex Annealing To generate the desired siRNA duplex, the two complementary strands were annealed by combining equimolar aqueous solutions of both strands. The mixtures were placed into a water bath at 70°C for 5 minutes and subsequently allowed to cool to ambient temperature within 2 h. The duplexes were lyophilized for 2 days and stored at -20°C. The duplexes were analyzed by analytical SEC HPLC on Superdex™ 75 Increase 5/150 GL column 5 x 153-158 mm (Cytiva) on a Dionex Ultimate 3000 (Thermo Fisher Scientific) HPLC system. Mobile phase consisted of 1x PBS containing 10% acetonitrile. An isocratic gradient was run in 10 min at a flow rate of 1.5 mL/min at room temperature. UV traces at 260 and 280 nm were recorded. Water (LC-MS grade) was purchased from Sigma-Aldrich and Phosphate- buffered saline (PBS; 10x, pH 7.4) was purchased from GIBCO (Thermo Fisher Scientific). Example 6: Alternative synthesis route for the conjugate building block TriGalNAc _Tether2

Conjugation of Tether 2 to a siRNA strand: TriGalNAc tether 2 (GalNAc-T2) conjugation at 5’- end or 3’-end Conjugation conditions

Pre-activation: To a solution of compound 15 (16 umol, 4 eq.) in DMF (160 μL) was added TFA-O-PFP (15 μl, 21 eq.) followed by DIPEA (23 μl, 32 eq.) at 25°C. The tube was shaken for 2 h at 25°C. The reaction was quenched with H2O (10 μL). Coupling: The resulting mixture was diluted with DMF (400 μl), followed by addition of oligo- amine solution (4.0 μmol in 10 x PBS, pH 7.4, 500 μL; final oligo concentration in organic and aqueous solution: 4 µmol/ml = 4 mM). The tube was shaken at 25°C for 16 h and the reaction was analysed by LCMS. The resulting mixture was treated with 28% NH4OH (4.5 ml) and shaken for 2 h at 25°C. The mixture was analysed by LCMS, concentrated, and purified by IP- RP HPLC to produce the oligonucleotides conjugated to tether 2 GalNAc. 5’-GalNAc-T2 conjugates

3’-GalNAc-T2 conjugates

Example 7: Solid phase synthesis method: scale ≤1µmol Syntheses of siRNA sense and antisense strands were performed on a MerMade192X synthesiser with commercially available solid supports made of controlled pore glass with universal linker (Universal CPG, with a loading of 40 μmol/g; LGC Biosearch or Glen Research). RNA phosphoramidites were purchased from ChemGenes or Hongene. The 2'-O-Methyl phosphoramidites used were the following: 5'-(4,4'-dimethoxytrityl)-N- benzoyl-adenosine 2'-O-methyl-3'- [(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'- (4,4'-dimethoxytrityl)-N-acetyl-cytidine 2'-O-methyl-3'- [(2-cyanoethyl)-(N,N-diisopropyl)]- phosphoramidite, 5'-(4,4'-dimethoxytrityl)-N-isobutyryl-guanosine 2'-O-methyl-3'-[(2- cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'-(4,4'-dimethoxytrityl)-uridine 2'-O-methyl- 3'-[(2-cyanoethyl)- (N,N-diisopropyl)]-phosphoramidite. The 2’-F phosphoramidites used were the following: 5'-dimethoxytrityl-N-benzoyl- deoxyadenosine 2'-fluoro-3'-[(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'- dimethoxytrityl-N-acetyl-deoxycytidine 2'-fluoro-3'-[(2-cyanoethyl)-(N,N-diisopropyl)]- phosphoramidite, 5'-dimethoxytrityl-N-isobutyryl-deoxyguanosine 2'-fluoro-3'- [(2-cyanoethyl)- (N,N-diisopropyl)]-phosphoramidite and 5'-dimethoxytrityl-deoxyuridine 2'-fluoro-3'-[(2- cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite. All phosphoramidites were dissolved in anhydrous acetonitrile (Honeywell Research Chemicals) at a concentration of 0.05M, except 2’-O-methyl-uridine phosphoramidite which was dissolved in DMF/MeCN (1:4, v/v). Iodine at 0.02M in acetonitrile/Pyridine/H₂O (DNAchem) was used as oxidizing reagent. Thiolation for phosphorothioate linkages was performed with 0.2 M PADS (TCI) in acetonitrile/pyridine 1:1 v/v.5-Ethyl thiotetrazole (ETT), 0.25M mM in acetonitrile was used as activator solution. Inverted abasic phosphoramidite, 3-O-Dimethoxytrityl-2-deoxyribose-5-[(2-cyanoethyl)-(N, N- diisopropyl)]-phosphoramidite were purchased from Chemgenes (ANP-1422) or Hongene (OP- 040). At each cycle, the DMT was removed by deblock solution, 3% TCA in DCM (DNAchem). The coupling time was 180 seconds. The oxidizer contact time was set to 80 seconds and thiolation time was 2*100 seconds. At the end of the synthesis, the oligonucleotides were cleaved from the solid support using a NH₄OH:EtOH solution 4:1 (v/v) for 20 hours at 45°C (TCI). The solid support was then filtered off, the filter was thoroughly washed with H2O and the volume of the combined solution was reduced by evaporation under reduced pressure. Oligonucleotide were treated to form the sodium salt by ultracentrifugation using Amicon Ultra- 2 Centrifugal Filter Unit; PBS buffer (10x, Teknova, pH 7.4, Sterile) or by EtOH precipitation from 1M sodium acetate. The single strands identity were assessed by MS ESI- and then, were annealed in water to form the final duplex siRNA and duplex purity were assessed by size exclusion chromatography. Example 8: Solid phase synthesis method: scale ≥5 µmol Syntheses of siRNA sense and antisense strands were performed on a MerMade12 synthesiser with commercially available solid supports made of controlled pore glass with universal linker (Universal CPG, with a loading of 40 μmol/g; LGC Biosearch or Glen Research) at 5 µmol scale. Sense strand destined to 3' conjugation were sytnthesised at 12 µmol on 3'-PT-Amino- Modifier C6 CPG 500 Å solid support with a loading of 86 µmol/g (LGC). RNA phosphoramidites were purchased from ChemGenes or Hongene. The 2'-O-Methyl phosphoramidites used were the following: 5'-(4,4'-dimethoxytrityl)-N- benzoyl-adenosine 2'-O-methyl-3'- [(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'- (4,4'-dimethoxytrityl)-N-acetyl-cytidine 2'-O-methyl-3'- [(2-cyanoethyl)-(N,N-diisopropyl)]- phosphoramidite, 5'-(4,4'-dimethoxytrityl)-N-isobutyryl-guanosine 2'-O-methyl-3'-[(2- cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'-(4,4'-dimethoxytrityl)-uridine 2'-O-methyl- 3'-[(2-cyanoethyl)- (N,N-diisopropyl)]-phosphoramidite. The 2’-F phosphoramidites used were the following: 5'-dimethoxytrityl-N-benzoyl- deoxyadenosine 2'-fluoro-3'-[(2-cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite, 5'- dimethoxytrityl-N-acetyl-deoxycytidine 2'-fluoro-3'-[(2-cyanoethyl)-(N,N-diisopropyl)]- phosphoramidite, 5'-dimethoxytrityl-N-isobutyryl-deoxyguanosine 2'-fluoro-3'- [(2-cyanoethyl)- (N,N-diisopropyl)]-phosphoramidite and 5'-dimethoxytrityl-deoxyuridine 2'-fluoro-3'-[(2- cyanoethyl)-(N,N-diisopropyl)]-phosphoramidite. Inverted abasic phosphoramidite, 3-O-Dimethoxytrityl-2-deoxyribose-5-[(2-cyanoethyl)-(N, N- diisopropyl)]-phosphoramidite were purchased from Chemgenes (ANP-1422) or Hongene (OP- 040). All phosphoramidites were dissolved in anhydrous acetonitrile (Honeywell Research Chemicals) at a concentration of 0.05M, except 2’-O-methyl-uridine phosphoramidite which was dissolved in DMF/MeCN (1:4, v/v). Iodine at 0.02M in acetonitrile/Pyridine/H2O (DNAchem) was used as oxidizing reagent. Thiolation for phosphorothioate linkages was performed with 0.2 M PADS (TCI) in acetonitrile/pyridine 1:1 v/v.5-Ethyl thiotetrazole (ETT), 0.25M mM in acetonitrile was used as activator solution. At each cycle, the DMT was removed by deblock solution, 3% TCA in DCM (DNAchem). For strands synthesised on universal CPG the coupling was performed with 8 eq. of amidite for 130 seconds. The oxidation time was 47 seconds, the thiolation time was 210 seconds. For strands synthesised on 3'-PT-Amino-Modifier C6 CPG the coupling was performed with 8 eq. of amidite for 2*150 seconds. The oxidation time was 47 seconds, the thiolation time was 250 seconds At the end of the synthesis, the oligonucleotides were cleaved from the solid support using a NH4OH:EtOH solution 4:1 (v/v) for 20 hours at 45°C (TCI). The solid support was then filtered off, the filter was thoroughly washed with H₂O and the volume of the combined solution was reduced by evaporation under reduced pressure. Oligonucleotide were treated to form the sodium salt by EtOH precipitation from 1M sodium acetate. The single strand oligonucleotides were purified by IP-RP HPLC on Xbridge BEH C185 µm, 130 Å, 19x150 mm (Waters) column with an increasing gradient of B in A. Mobile phase A: 240 mM HFIP, 7 mM TEA and 5% methanol in water; mobile phase B: 240 mM HFIP, 7 mM TEA in methanol. The single strands purity and identity were assessed by UPLC/MS ESI- on Xbridge BEH C18 2.5 µm, 3x50 mm (Waters) column with an increasing gradient of B in A. Mobile phase A: 100 mM HFIP, 5 mM TEA in water; mobile phase B: 20% mobile phase A: 80% Acetonitrile (v/v). Sense strands were conjugated as per protocol provided in any of Examples 2, 4, 6. Sense and Antisense strands were then annealed in water to form the final duplex siRNA and duplex purity were assessed by size exclusion chromatography. The present invention is not intended to be limited in scope to the particular disclosed embodiments, which are provided, for example, to illustrate various aspects of the invention. Various modifications to the compositions and methods described will become apparent from the description and teachings herein. Such variations may be practiced without departing from the true scope and spirit of the disclosure and are intended to fall within the scope of the present disclosure. Example 9: Dose-response for Inhibition of SLC25A5 Expression in Human Huh7 Cells Huh7 cells (human hepatocyte-derived cell line, obtained from JCRB Cell Bank) were maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% FBS and 1% non-essential amino acids at 37˚C, 5% CO₂, 95% humidity. Cells were transfected with siRNA duplexes targeting either SLC25A5 mRNA or a negative control siRNA (siRNA-control; sense strand 5’- _{GCCTGTACCAAGGCTTTAA}-3’ (SEQ ID NO:1383), antisense strand 5’- _{TTAAAGCCTTGGTACAGGC}-3’ (SEQ ID NO:1382)) in a 6-point, log dose response curve to give final in assay concentrations of 3nM to 0.03pM. Transfection was carried out by diluting Lipofectamine RNAiMAX (ThermoFisher) in Opti-MEM (ThermoFisher) medium at a ratio of 48.5:1.5. This solution was added to an equal volume of siRNA, diluted to the required concentration in phosphate buffered saline. The lipofectamine RNAiMAX and siRNA mixture was incubated at room temperature for 15 minutes before 20 µL was added to wells of a 96 well plate. Huh7 cells were dissociated from flasks using trypsin and resuspended at a density of 200,000 cells/mL.100 µL of Huh7 cell suspension was added to each well of the siRNA- containing 96-well plates. Cells were incubated for 24 hours at 37˚C, 5% CO2,95% humidity. Each siRNA was tested in triplicate wells and on two separate days for a total of six replicates. Intracellular RNA was isolated using an RNeasy kit (Qiagen) according to the manufacturer’s instructions. cDNA synthesis was performed using a FastKing RT kit, with gDNase (Tiangen). Target cDNA was the quantified by qPCR on an ABI Prism 7900HT or ABI QuantStudio 7 with primers specific for human SLC25A5 (forward: ACTGACATCATGTACACAGGCAC (SEQ ID ^NO:1384), reverse: ACCCATGCCTCTGAGAACATT (SEQ ID NO:1385)^{) and human GAPDH} ^(forward: GAAGGTGAAGGTCGGAGTC (SEQ ID NO:1386)^{, reverse:} _{GAAGATGGTGATGGGATTTC (SEQ ID NO:1387)} ^{) using a SensiFAST SYBR Hi-ROX kit} (Meridian). qPCR was performed in duplicate on cDNA derived from each well and the mean Ct calculated. Relative SLC25A5 expression was calculated from mean Ct values using the comparative Ct (∆∆Ct) method, 229ormalized to GAPDH and relative to untreated cells. Maximum percent inhibition of SLC25A5 expression and pEC50 values (-log₁₀ of the EC50) were calculated using a four parameter (variable slope) model using NumPy (Python). Results are shown in Table 6. Sequences of RNAi molecules are depicted in the relevant Tables herein. Table 6 – Results of dose-response experiments for inhibition of SLC25A5 mRNA expression in human Huh7 cells. Observed and fitted pEC50s are reported with observed minimum and maximum relative expression values (relative to medium control) for two experimental replicates (repeated on separate days with three repeats per day). ETXM ID Minimum r1 Maximum r1 pEC50 r1 Minimum r2 Maximum r2 pEC50 r2 ETX-M00001351 0.095738517 1.012076322 9.74 0.16593971 1.135465148 9.46 ETX-M00001352 0.068977171 0.832613609 10.36 0.107726125 1.031889622 10.19 ETX-M00001353 0.076601856 0.942804039 10.09 0.105081317 0.866486243 9.79 ETX-M00001354 0.04160111 0.352837401 12.42 0.054758242 0.528360743 10.99 ETX-M00001355 0.286834824 1.105769257 9.36 0.422953861 1.267175414 9.08 ETX-M00001356 0.062109246 0.683699132 10.89 0.082971501 0.990778092 10.6 ETX-M00001357 0.260371194 1.047615584 9.05 0.330270419 1.227520719 9.11 ETX-M00001358 0.126012018 1.005286574 10.49 0.097256411 0.933587755 10.17 ETX-M00001359 0.086718222 0.886522538 10.16 0.143556553 1.077345717 9.88 ETX-M00001360 0.197501054 1.021858054 9.44 0.444312718 1.286204781 9.33 ETX-M00001361 0.155005218 1.010333551 9.41 0.337064444 1.310022413 8.88 ETX-M00001362 0.602601339 1.065764399 9.79 0.782613101 1.537826561 9.69 ETX-M00001363 0.267572294 1.072128134 9.35 0.294825935 0.993647402 9.12 ETX-M00001364 0.06269171 0.884419453 10.17 0.099587992 0.789694685 10.08 ETX-M00001365 0.162554032 1.032331404 9.49 0.230453664 0.874107567 9.12 ETX-M00001366 0.6460043 1.101955001 8.88 0.560386396 0.86269628 6.93 ETX-M00001367 0.071999043 0.945858821 9.64 0.153954817 1.043108396 9.61 ETX-M00001368 0.308068257 0.9872225 9.47 0.405284264 1.139893375 9.4 ETX-M00001369 0.156575267 0.90043545 9.83 0.225683816 1.020341168 9.72 ETX-M00001370 0.470403615 1.014232608 9.5 0.563112577 1.122335299 9.31 ETX-M00001371 0.098907568 0.787402535 10.35 0.153074794 0.798991053 10.32 ETX-M00001372 0.232940452 20.51401011 9.15 0.29985096 0.937317894 9.23 ETX-M00001373 0.672653114 1.084781814 8.98 0.709952949 1.044549135 6.47 ETX-M00001374 0.129831319 0.858799681 10.42 0.184951482 0.991071046 10.47 ETX-M00001375 0.638666505 1.178135966 9.09 0.833987501 1.394790706 8.96 ETX-M00001376 0.173010986 1.014074132 9.55 0.271870984 1.159800931 9.44 ETX-M00001377 0.029866025 0.461845856 11.42 0.082112622 0.405412255 11.37 ETX-M00001378 0.033539757 0.391435718 11.38 0.074342373 0.394622732 11.41 ETX-M00001379 0.163436084 0.971055681 9.56 0.205951766 0.969382997 9.48 ETX-M00001380 0.670568552 1.034799511 9.0 0.703395629 1.344662124 8.94 ETX-M00001381 0.110474151 0.94017161 9.78 0.166686735 0.848694146 9.75 ETX-M00001382 0.122417733 1.010395959 9.73 0.270001915 1.09501631 9.56 ETX-M00001383 0.221764768 1.090018663 9.27 0.327849656 1.16764907 9.0 ETX-M00001384 0.287275636 1.053461449 9.3 0.407959766 1.098005644 9.4 ETX-M00001385 0.216868684 1.02420622 9.14 0.279940004 1.109063691 9.31 ETX-M00001386 0.148103725 1.112208683 10.22 0.201395101 1.026732832 9.9 ETX-M00001387 0.452045611 1.214447835 9.11 0.440417532 1.065952197 8.99 ETX-M00001388 0.800140403 1.158463785 9.01 0.76715024 0.967428082 8.9 ETX-M00001389 0.800162618 1.419723412 0.0 0.773333933 1.392230032 9.5 ETX-M00001390 0.78279321 1.267998923 9.0 0.678338137 1.053988924 9.01 ETX-M00001391 0.205170765 1.226167435 9.59 0.333949624 1.105578037 9.72 ETX-M00001392 0.158295637 1.087596385 9.47 0.257646919 0.954021904 9.08 ETX-M00001393 0.194066175 3.342535483 9.04 0.313998274 0.971069253 9.22 ETX-M00001394 0.180283743 1.118030944 9.28 0.260329094 1.082753479 9.18 ETX-M00001395 0.309352861 1.137365201 9.28 0.52067815 1.193534411 9.11 ETX-M00001396 0.40019968 1.13373136 9.49 0.563866817 1.334643135 8.99 ETX-M00001397 0.073086557 0.940567178 10.12 0.146815712 1.080179879 9.62 ETX-M00001398 0.496678766 1.275410449 9.11 0.569827975 1.224383752 9.0 ETX-M00001399 0.646326737 1.261626778 8.25 0.783692857 1.127135396 9.37 ETX-M00001400 0.28591739 1.049050528 10.22 0.455156391 1.119328067 9.26 ETX-M00001401 0.335759007 1.305561354 9.14 0.548618029 1.073617382 8.98 ETX-M00001402 0.660927117 1.250923252 -0.32 0.811938783 1.135108226 ? ETX-M00001403 0.272226606 1.247723091 9.26 0.332815624 1.063614207 9.1 ETX-M00001404 0.94795512 1.325845624 8.4 0.882313118 1.159683253 ? ETX-M00001405 0.216376035 1.081756406 9.38 0.353142531 1.074248491 9.08 ETX-M00001406 0.425361623 1.388509882 9.03 0.520891691 1.290040521 9.0 ETX-M00001407 0.360201247 1.028556712 9.36 0.530895788 1.15606022 8.54 ETX-M00001408 0.790249405 1.164609515 9.04 0.822216806 1.000182763 8.25 ETX-M00001409 0.384042177 1.109734635 9.07 0.588229001 0.984025099 8.11 ETX-M00001410 0.458907902 1.110918523 8.99 0.661359549 1.203285258 8.99 ETX-M00001411 0.75868181 1.269040526 8.79 0.810606369 1.180662648 9.95 ETX-M00001412 0.15105394 1.235349129 9.46 0.260396517 0.975273705 8.96 ETX-M00001413 0.160985877 1.678177568 9.61 0.26980012 0.961196934 8.94 ETX-M00001414 0.768241259 1.170215924 ? 0.715623854 1.158138413 7.59 ETX-M00001415 0.158415985 0.863652199 9.01 0.327047507 1.082230484 9.23 ETX-M00001416 0.501585231 0.925841695 8.16 0.696435893 1.067735112 8.99 ETX-M00001417 0.079029021 0.804039145 10.19 0.129634235 0.972886998 9.97 ETX-M00001418 0.215872805 0.953565365 9.4 0.297826739 0.997706738 9.21 ETX-M00001419 0.934639334 1.346565751 0.25 0.93139409 1.274261754 0.0 ETX-M00001420 0.612369112 1.827760146 9.14 0.657453694 1.36190322 8.99 ETX-M00001421 0.091032944 0.929188108 9.92 0.13364019 1.220179968 9.78 ETX-M00001422 0.101499366 1.062852058 9.77 0.139991669 1.09309642 9.63 ETX-M00001423 0.030768893 0.602673809 10.94 0.114329435 0.807419623 10.28 ETX-M00001424 0.041897446 0.706970326 10.98 0.119111702 0.787803206 10.56 ETX-M00001425 0.053728018 0.473666552 11.18 0.130755094 0.684291085 10.44 ETX-M00001426 0.027792257 0.69772576 10.99 0.1330014 0.805546258 10.34 ETX-M00001427 0.042372721 0.768245564 10.56 0.15004026 0.98645508 9.71 ETX-M00001428 0.038274421 0.540155754 11.12 0.131942785 0.810898502 10.3 ETX-M00001429 0.071583565 0.925950293 9.9 0.291507299 1.13672904 9.45 ETX-M00001430 0.023816791 0.215234943 -78.66 0.135367433 0.607962593 10.78 ETX-M00001431 0.435973061 1.411804601 8.46 0.694683789 1.248311443 -0.01 ETX-M00001432 0.177808018 1.234507806 9.88 0.338993675 1.056091296 9.3 ETX-M00001433 0.344988132 1.299711934 9.0 0.627298879 1.201312427 9.02 ETX-M00001434 0.028180714 0.40484356 11.55 0.103829996 0.703970412 10.3 ETX-M00001435 0.216966986 1.11371214 9.77 0.330384089 1.112557791 9.8 ETX-M00001436 0.115218504 0.707893402 10.87 0.142475213 0.768763289 10.65 ETX-M00001437 0.103217781 0.70456761 10.07 0.143716816 1.035354144 10.14 ETX-M00001438 0.132112484 1.005363409 9.72 0.218409608 1.10831212 9.78 ETX-M00001439 0.221764768 1.090018663 9.27 0.123223569 0.957429878 9.87 ETX-M00001440 0.287275636 1.053461449 9.3 0.163879147 0.817019676 10.42 ETX-M00001441 0.216868684 1.02420622 9.14 0.306020744 1.065748137 9.97 ETX-M00001442 0.148103725 1.112208683 10.22 0.576438032 1.124823589 8.99 ETX-M00001443 0.452045611 1.214447835 9.11 0.2936311 1.049463941 9.54 ETX-M00001444 0.800140403 1.158463785 9.01 0.365630694 1.172872599 9.29 ETX-M00001445 0.800162618 1.419723412 0.0 0.197824563 0.916524711 9.95 ETX-M00001446 0.78279321 1.267998923 9.0 0.700984039 1.099422182 8.58 ETX-M00001447 0.100102106 0.854701522 10.39 0.168763678 0.751253787 10.26 ETX-M00001448 0.15894435 1.043784315 9.89 0.223273212 0.883386035 10.42 ETX-M00001449 0.249364194 1.077980073 9.52 0.351716637 0.93335442 9.79 ETX-M00001450 0.368410731 1.275252679 9.17 0.55019584 1.169170461 8.93 ETX-M00001451 0.308919609 1.192696082 8.97 0.490813235 1.211992211 9.01 ETX-M00001452 0.238825279 1.127361753 9.5 0.267021778 1.07609102 9.47 ETX-M00001453 0.217260602 1.051652684 9.46 0.230084869 1.042460178 9.37 ETX-M00001454 0.234446288 1.169298234 9.41 0.271443049 1.179742065 9.19 ETX-M00001455 0.746843593 1.367585649 8.29 0.968150833 1.336735444 -0.17 ETX-M00001456 0.183031984 1.064959801 9.29 0.289254915 1.293047811 8.99 ETX-M00001457 0.238616955 1.114849179 9.25 0.397275929 1.264765125 9.16 ETX-M00001458 0.210942479 1.125762774 9.28 0.303795657 1.299295709 9.11 ETX-M00001459 0.489740872 1.694856765 8.55 0.584916867 1.104498189 8.98 ETX-M00001460 0.285056768 1.294302518 9.14 0.441451608 1.188362675 9.08 ETX-M00001461 0.110882254 0.727086504 10.3 0.17207752 0.838528119 10.5 ETX-M00001462 0.200805398 1.214763555 9.35 0.280317345 1.012046941 9.24 ETX-M00001463 0.320540907 1.810561879 8.88 0.402634571 1.290068698 9.2 ETX-M00001464 0.159637206 1.271535485 9.55 0.265979152 1.23028713 9.39 ETX-M00001465 0.454641221 1.443074714 9.0 0.56238986 1.35228576 9.0 ETX-M00001466 0.171636779 1.335353607 9.74 0.196300204 1.171968934 9.57 ETX-M00001467 0.778757355 1.553862978 8.43 0.851261054 1.271042398 8.29 ETX-M00001468 0.401989061 1.057827275 9.46 0.577060998 1.186666801 9.73 ETX-M00001469 0.396568651 1.171359199 9.16 0.523167163 1.175507738 9.18 ETX-M00001470 0.113717947 0.907199722 9.62 0.218182315 1.063325306 9.57 ETX-M00001471 0.120533094 0.828923044 10.57 0.244872851 1.072996958 9.86 ETX-M00001472 0.113811368 0.815070157 9.95 0.240436689 1.012257113 10.24 ETX-M00001473 0.283579604 0.963540287 9.45 0.426049534 1.120006437 9.28 ETX-M00001474 0.248817244 1.007768806 9.29 0.364067497 1.049510075 9.27 ETX-M00001475 0.121434646 1.137384843 10.19 0.220525582 1.722171527 9.66 ETX-M00001476 0.174490948 0.988894599 9.4 0.295644685 1.17090225 9.28 ETX-M00001477 0.171943987 1.188054484 9.66 0.274977759 1.18087502 9.28 ETX-M00001478 0.177969128 1.021092284 9.67 0.331721708 1.093505269 9.62 ETX-M00001479 0.092930861 0.824855043 10.54 0.204343598 0.969385677 9.84 ETX-M00001480 0.141566218 0.745036939 10.32 0.233151152 0.895095386 9.84 ETX-M00001481 0.138921202 0.736618352 10.51 0.226481701 0.841155311 10.13 ETX-M00001482 0.388745982 1.162255498 9.06 0.568413041 1.123140442 9.12 ETX-M00001483 0.072424585 0.938831484 10.58 0.109836142 0.783990627 10.89 ETX-M00001484 0.385456815 1.337734578 8.99 0.407593444 1.115493506 8.59 ETX-M00001485 0.644075114 1.33239794 9.0 0.696154137 1.207585965 9.09 ETX-M00001486 0.209202376 1.331221759 9.02 0.294101713 1.014341711 9.77 ETX-M00001487 0.108356429 0.947812285 10.31 0.166435673 1.481408137 9.55 ETX-M00001488 0.47465733 1.14219708 8.96 0.628623935 1.900515639 9.0 ETX-M00001489 0.434499739 1.167375381 9.13 0.440779731 1.591624543 8.71 ETX-M00001490 0.19610501 1.205713394 9.56 0.274297457 1.103030792 9.3 ETX-M00001491 0.426861836 1.463737558 8.63 0.643380462 2.286311572 8.46 ETX-M00001492 0.224798533 1.081459718 9.49 0.233644026 1.400814023 9.2 ETX-M00001493 0.906094114 1.191672581 9.5 0.976893745 1.264085464 -1.4 ETX-M00001494 0.08192495 0.94445998 10.19 0.17525009 0.993388621 10.2 ETX-M00001495 0.080857184 0.597337943 10.8 0.049498544 0.491324095 11.23 ETX-M00001496 0.094063464 0.764050166 10.18 0.071457482 0.720299294 10.4 ETX-M00001497 0.075678813 0.50449811 11.45 0.063012829 0.455447572 11.57 ETX-M00001498 0.510534822 1.259204211 8.99 0.463093976 1.048341966 9.01 ETX-M00001499 0.418784302 1.1920872 9.0 0.374906799 1.073669819 9.03 ETX-M00001500 0.200723546 1.060111323 9.52 0.175118984 0.899436225 9.63 ETX-M00001501 0.882334298 1.226476653 0.16 0.848469024 1.095005712 -5.02 ETX-M00001502 0.126837941 0.919482021 9.95 0.115173834 0.973821256 10.23 ETX-M00001503 0.231044552 1.082675933 9.24 0.176195581 1.075046561 9.61 ETX-M00001504 0.114326676 0.733485819 10.86 0.083699606 0.693000187 10.9 ETX-M00001505 0.197915702 1.103229148 9.48 0.13713965 0.998946726 9.9 ETX-M00001506 0.176746491 0.987150514 9.97 0.135915382 0.873482162 10.34 ETX-M00001507 0.08160249 0.71798817 10.37 0.087207447 0.670526217 10.66 ETX-M00001508 0.364040402 1.280998227 9.3 0.348836799 1.050224419 9.3 ETX-M00001509 0.31606101 0.979201368 9.69 0.313530488 0.975783603 9.52 ETX-M00001510 0.071968429 0.581647292 10.78 0.060296712 0.602027438 10.82 ETX-M00001511 0.144734418 1.030898602 9.95 0.10386541 0.925246827 10.2 ETX-M00001512 0.104870364 0.75616524 10.37 0.059908818 0.516885518 11.64 ETX-M00001513 0.179163038 1.072057612 9.61 0.105146715 0.742414703 9.93 ETX-M00001514 0.112349798 0.769550516 10.29 0.071720467 0.693729042 10.6 ETX-M00001515 0.067451248 0.568081347 10.82 0.114948551 0.602883724 11.12 ETX-M00001516 0.226102671 1.151276558 9.24 0.272063757 1.323051929 9.3 ETX-M00001517 0.130588516 0.890962698 9.83 0.138718171 1.147955078 9.68 ETX-M00001518 0.168426311 1.001374024 9.58 0.248305081 1.46112812 9.24 ETX-M00001519 0.809829349 1.456027731 0.0 0.749409682 1.281428091 8.05 ETX-M00001520 0.179840061 1.141350447 9.62 0.201821884 1.052988019 10.21 ETX-M00001521 0.203198525 1.289622065 9.07 0.180323649 1.117605884 9.29 ETX-M00001522 0.077505813 0.685343817 10.34 0.130822448 0.877167048 10.83 ETX-M00001523 0.117059655 0.981224957 9.91 0.105714855 0.803061856 10.02 ETX-M00001524 0.103347245 0.893605415 10.29 0.117905549 0.809822999 10.02 ETX-M00001525 0.13029678 0.941109066 9.54 0.160804315 0.832443362 9.61 ETX-M00001526 0.062744305 0.520379788 11.18 0.126635651 0.597941198 10.88 ETX-M00001527 0.099571218 0.465361604 11.17 0.072424535 0.507056471 11.76 ETX-M00001528 0.149902577 0.935776294 9.56 0.14818156 0.973651465 9.73 ETX-M00001529 0.732102262 1.130692465 9.0 0.634056731 0.979029905 9.39 ETX-M00001530 0.347540036 0.993951999 9.44 0.309187379 0.881776133 9.66 ETX-M00001531 0.493193123 1.35093671 9.2 0.373880033 1.205940588 9.4 ETX-M00001532 0.17481454 0.873636227 9.97 0.173560413 1.029329111 9.82 ETX-M00001533 0.10594013 0.862763224 10.61 0.124919693 0.800477542 9.94 ETX-M00001534 0.456821858 1.377927122 9.43 0.458928031 1.28999398 9.32 ETX-M00001535 0.157627223 0.765275769 10.57 0.127689025 0.667310419 10.54 ETX-M00001536 0.685316166 1.082851287 9.04 0.597891015 1.019780343 9.06 ETX-M00001537 0.381668923 1.062754689 9.09 0.396259914 1.000956262 8.73 ETX-M00001538 0.180573755 1.055378958 9.51 0.201395581 0.991416335 9.48 ETX-M00001539 0.197517396 0.744389507 10.38 0.16862501 0.775077746 10.54 ETX-M00001540 0.563176143 1.011627826 9.45 0.64089012 1.314587739 9.51 ETX-M00001541 0.197125268 0.945899049 9.98 0.206910811 1.109952497 9.59 ETX-M00001542 0.542663818 1.05735558 8.41 0.719819173 1.258341437 8.9 ETX-M00001543 0.777761827 1.26233632 9.0 0.554219931 1.108749535 8.72 ETX-M00001544 0.89375873 1.302943327 8.41 0.788780887 1.163578464 8.43 ETX-M00001545 0.576131016 1.119549124 9.08 0.503221337 1.264839213 8.97 ETX-M00001546 0.483426456 0.883052326 8.78 0.308175911 1.054578142 9.37 ETX-M00001547 0.480114307 1.051566679 8.54 0.359316228 1.094484103 8.78 ETX-M00001548 0.70132732 1.065456235 9.02 0.602001297 1.04393653 8.85 ETX-M00001549 0.386814514 0.993180839 9.33 0.288733418 0.998632663 9.19 ETX-M00001550 0.184467342 0.910668466 9.72 0.145861597 0.919265817 9.78 ETX-M00001551 0.386743581 0.991704529 9.25 0.367859285 0.974739364 9.29 ETX-M00001552 0.445317048 1.090403237 9.23 0.360788664 1.05755516 8.99 ETX-M00001553 0.741525263 1.205512199 9.02 0.486200881 0.930696646 8.29 ETX-M00001554 0.494077496 1.150159346 9.29 0.349603107 0.900009674 8.8 ETX-M00001555 0.178659403 0.848413657 9.97 0.170464758 0.939955207 9.57 ETX-M00001556 0.828543443 1.114700202 10.99 0.856549135 1.096966838 9.47 ETX-M00001557 0.470368629 1.276291834 9.27 0.338719844 1.019021445 9.0 ETX-M00001558 0.171496525 0.771925354 10.13 0.078951578 0.753412781 10.25 ETX-M00001559 0.181284051 0.908321484 9.55 0.168754413 1.14125101 9.37 ETX-M00001560 0.108847895 0.563787309 11.12 0.094853422 0.844001013 10.32 ETX-M00001561 0.148083049 0.650576181 10.49 0.119327018 0.933218386 10.08 ETX-M00001562 0.579285681 0.989126818 9.01 0.463948037 1.139016097 8.89 ETX-M00001563 0.098812665 0.941552386 10.34 0.214112909 1.162380727 9.47 ETX-M00001564 0.052725485 0.833096066 10.67 0.107121702 0.914576774 9.74 ETX-M00001565 0.047907714 0.581064923 10.91 0.067270985 0.552200534 10.47 ETX-M00001566 0.214032943 0.818838176 9.89 0.311818988 0.981055179 9.2 ETX-M00001567 0.199889178 0.968529415 10.04 0.319098269 1.409166113 9.13 ETX-M00001568 0.176969332 1.06278721 9.73 0.29353383 1.103629318 9.04 ETX-M00001569 0.407251176 1.186700827 8.54 0.672469941 1.17041867 8.97 ETX-M00001570 0.115382895 0.860648931 10.34 0.164460348 0.92337603 9.32 ETX-M00001571 0.05473803 0.438738377 11.93 0.084787702 0.633491573 10.88 ETX-M00001572 0.067802596 0.617781602 10.57 0.18910512 0.906705118 9.59 ETX-M00001573 0.312545863 1.17445612 9.2 0.708548657 1.189540452 9.29 ETX-M00001574 0.057184217 0.552280966 10.67 0.115227409 0.824190268 9.92 ETX-M00001575 0.04317709 0.27527029 11.85 0.09050152 0.772109748 10.47 ETX-M00001576 0.152649557 0.841047573 9.93 0.400363493 1.223773728 9.27 ETX-M00001577 0.287805848 0.877207354 9.48 0.512663586 1.095392064 8.83 ETX-M00001578 0.099624046 0.526723164 10.86 0.197297808 0.983353018 10.02 ETX-M00001579 0.863418654 1.46395648 10.84 0.84901866 1.227113901 -6.58 ETX-M00001580 0.403486041 1.096554233 9.66 0.520411651 1.02518741 9.03 ETX-M00001581 0.320598408 0.811449753 9.81 0.425870046 0.928399188 9.2 ETX-M00001582 0.215381862 0.820981528 9.58 0.256176522 0.914370438 9.42 ETX-M00001583 0.392932707 1.360432302 9.32 0.412439429 1.216383934 8.99 ETX-M00001584 0.402751165 1.132555042 9.3 0.408138628 1.048518391 9.07 ETX-M00001585 0.08435408 0.383878766 11.68 0.086676618 0.357384673 11.58 ETX-M00001586 0.269361892 0.948358322 9.22 0.338865735 0.990278462 9.47 ETX-M00001587 0.277665435 1.143162503 9.2 0.378850337 1.078608968 8.59 ETX-M00001588 0.841480649 1.220938473 9.26 0.764889069 1.058900061 9.0 ETX-M00001589 0.208434212 0.892736613 9.4 0.298104578 0.797916085 9.03 ETX-M00001590 0.716619149 1.25745607 -4.12 0.784044223 0.987616219 26.18 ETX-M00001591 0.288322534 1.08649535 9.43 0.307111179 0.965734776 9.11 ETX-M00001592 0.201705314 1.083891991 9.42 0.374456992 0.890546244 9.08 ETX-M00001593 0.18228958 1.111277792 9.33 0.256884978 0.862583147 8.99 ETX-M00001594 0.205552739 1.155201884 9.14 0.361292556 0.90636084 8.58 ETX-M00001595 0.206440906 0.991323799 9.56 0.163368706 0.955356479 9.57 ETX-M00001596 0.589633448 2.132271683 8.97 0.639093563 1.181792348 8.95 ETX-M00001597 0.367440045 1.094506689 9.35 0.407310825 1.059163317 8.71 ETX-M00001598 0.655942506 1.235746886 9.53 0.831850723 1.240753963 8.92 ETX-M00001599 0.352272258 1.111112788 8.58 0.362658499 1.037247416 8.79 ETX-M00001600 0.248248305 1.097005509 9.12 0.223276615 0.888735217 9.17 ETX-M00001601 0.475783706 1.098854043 8.51 0.465953232 1.082429874 9.0 ETX-M00001602 0.509886049 1.118393415 8.55 0.50385973 1.026034017 8.8 ETX-M00001603 0.643839605 1.137055937 9.01 0.529177461 1.064149629 9.13 ETX-M00001604 0.504469772 1.118067066 9.02 0.464379123 1.059705967 9.18 ETX-M00001605 0.567162373 1.14875507 9.01 0.551503146 1.16342646 8.98 ETX-M00001606 0.208344328 0.89822559 9.3 0.226732801 0.919876777 9.14 ETX-M00001607 0.415849594 1.050395564 9.24 0.327137947 1.113661679 9.06 ETX-M00001608 0.808421575 1.046724469 9.02 0.772163102 1.236522954 9.11 ETX-M00001609 0.554494567 1.02478462 9.0 0.577937353 1.129353801 9.03 ETX-M00001610 0.39828919 1.021515595 9.14 0.36913694 1.096504339 9.28 ETX-M00001611 0.848566644 1.161099312 0.0 0.940978555 1.380812328 0.0 ETX-M00001612 0.892481009 1.244147363 9.08 0.88917405 1.240736924 0.0 ETX-M00001613 0.656003481 1.194774105 9.05 0.829473474 1.273747001 9.0 ETX-M00001614 0.742166545 1.243436536 9.0 0.812683918 1.209821119 9.01 ETX-M00001615 0.595695462 1.14232952 9.51 0.70827781 1.158039329 9.02 ETX-M00001616 0.904920762 1.476650471 8.99 0.774445301 1.154820201 9.01 ETX-M00001617 0.861617152 1.244273276 -0.01 0.856886335 1.063775894 ? ETX-M00001618 0.593920146 1.119007631 8.98 0.557719551 1.091604502 8.87 ETX-M00001619 0.517851725 1.515200255 8.96 0.373553248 1.145052949 8.99 ETX-M00001620 0.85505106 1.147959289 8.99 0.733229539 1.166700543 8.97 ETX-M00001621 0.589689324 1.183170083 8.73 0.613296368 1.044645764 9.01 ETX-M00001622 0.892328287 1.071820251 9.71 0.826525258 1.080202515 9.1 ETX-M00001623 0.36492363 1.116179441 8.78 0.376059882 1.087345416 8.96 ETX-M00001624 0.422346201 0.94353241 8.85 0.405757963 1.066069735 8.82 ETX-M00001625 0.257167276 1.085491538 9.11 0.321340742 1.080066253 8.93 ETX-M00001626 0.32109742 0.969305592 9.13 0.804305401 1.144015273 8.78 Example 10: Pharmacological studies in normal mice In vivo pharmacology study with five selected GalNAc-siRNAs The pharmacodynamic activity of five selected ANT2 GalNAc-siRNAs was measured in vivo. Thirty-two C57BL/6 male mice were allocated for each of the five GalNAc-siRNAs, ETX- M00001397, ETX-M00001570, ETX-M00001378, ETX-M00001513, and ETX-M00001527.20 mice were allocated as a control group (saline) and 16 mice were allocated for a negative control siRNA group (ETXM1198). Mice were subcutaneously dosed with ETXMs (1 mg/kg or 3 mg/kg) on day 0, defined as the day mice were first dosed. Four mice from saline control group were sacrificed on day 0 prior to dosing and subsequently, four mice in each treatment group at each dose level were sacrificed on day 7, 14, 21, and 28. Upon termination, liver tissues and plasma samples were harvested for further analysis. SLC25A5 mRNA knockdown in mouse liver Harvested liver samples were used to measure the SLC25A5 mRNA knockdown level by RT- qPCR. Upon collection, each tissue was treated with RNAlater and stored at 4 °C overnight then at -80 °C until the further analysis. Liver tissues were homogenized with TRIZOL for RNA extraction. RNA samples, adjusted to 400 ng/µL, were reverse transcribed to cDNA using FastKing RT Kit, manufactured by TIANGEN. After reverse transcription, real-time quantitative PCR may be performed using an ABI Prism 7900HT to detect the relative abundance of SLC25A5 mRNA normalized to the housekeeping gene GAPDH. The expression of the target gene in each test sample may be determined by relative quantitation using the comparative Ct (ΔΔCt) method. This method measures the Ct differences (ΔCt) between target gene and housekeeping gene. The formula is as follows: ΔCt = average Ct of SLC25A5–average Ct of GAPDH, ΔΔCt=ΔCt (sample) – average ΔCt (untreated control), relative expression of target gene mRNA = 2-ΔΔCt. ANT2 protein knockdown in mouse liver A second sample of liver tissue was used to measure ANT2 protein knockdown by LC-MS. Forty milligrams of mouse liver with 1.5 mL of RIPA buffer were used for protein extraction. Additionally, 1X of protease inhibitor, 1X of phosphatase inhibitor and 1X of PMSF were included in the RIPA buffer. QIAGEN Tissue Lyser was used to homogenize the liver until lysate becomes transparent. After high-speed centrifugation at 4 °C, the protein concentration in liver lysate was measured by BCA quantification kit. Three hundred microgram protein was taken from each liver lysate sample for digestion using the S-TrapTM 96-well MS sample prep kit according to the manufacturer’s instruction with one exception: DTT and IAA were used as reductant and alkylation reagents instead of TCEP and MMTS. For LC-MS/MS analysis, five hundred nanogram peptide was run on a 60 minute LC method in Easy Nano 1200 (mobile phase A: 0.1% formic acid in H2O, mobile phase B: 0.1% formic acid in 80% acetonitrile). The separation gradient is: 3-28%B from 0 to 40 min, 28-46%B from 40 to 45 min, 46 -100%B from 45-50 min and maintain at 100 %B to the end. A 25 cm of C18 column was used for peptide separation. The eluted peptide was analyzed in Orbitrap Eclipse at scan range of 350-1500 m/z with PRM-MS/MS method. The raw data was processed in Skyline and the peptide quality was manually checked. The SLC25a5 protein database from UniProt was uploaded as library search. The final selection of peptides should have the following characters: 1. Elution peak without tailing; 2. Well-matched product ions; 3. Quantified peak area greater than 1e6. Consequently, the following peptides, QIFLGGVDK and EQGVLSFWR, were chosen for SLC25a5 protein quantitation. Relative protein expression is calculated via time-matched normalisation of the average target peptide counts to the Vehicle Control group. Peptide counts corresponding to the reference protein (GAPDH) are not considered. The results of mRNA and protein knockdown are shown in Figure 10. Example 11: Pharmacological studies in Gubra-Amylin NASH (GAN) diet-induced obese (DIO) mice In this Example, the activity of ETX-312 (ETX-M00001378), an inhibitor of SLC25A5 expression, on metabolic parameters, hepatic pathology, and NAFLD Activity Score (NAS) including fibrosis stage in male biopsy-confirmed GAN DIO-NASH mice was tested. A total of 9 DIO-NASH groups (n=16) and 1 LEAN-CHOW group (n=10) of male C57BL/6JRj mice were fed 40% HFD, 40% carbohydrate (22% fructose), 2% Cholesterol (GAN) diet or normal chow (Altromin 1324) for 34 weeks prior to study start. All mice were pre-biopsied at week -4 and stratified based on liver biopsy (only animals with fibrosis stage =F2-F3, steatosis score =3 and inflammation score ≥2 were included). Mice were anesthetized by inhalation anesthesia using isoflurane (2-3%). A small abdominal incision was made in the midline and the left lateral lobe of the liver exposed. A cone shaped wedge of liver tissue (approximately 50 mg) was excised from the distal portion of the lobe and fixated in 10% neutral buffered formalin (10% NBF) for histology. The cut surface of the liver was instantly electrocoagulated using bipolar coagulation (ERBE VIO 100 electrosurgical unit). The liver was returned to the abdominal cavity, the abdominal wall sutured and the skin closed with staplers. For post-operative recovery, mice received carprofen (5mg/kg) administered subcutaneously on the day of the procedure and on post-operation days 1 and 2. Animals were randomized into groups based on fibrosis stage and picrosirius red (PSR) staining (% fractional area). Mice received a total of 12 weeks of dosing and were divided into the following groups: 1) LEAN-CHOW control (saline) (subcutanoues (SC), once weekly (QW)), 2) DIO-NASH control (saline) (SC, QW), 3) SiCtrl, 5 mg/kg (SC, QW), 4) ETX-312, 5 mg/kg (SC, QW), 5) Semaglutide, 30 nmol/kg (SC, once a day (QD)), 6) Semaglutide, 30 nmol/kg (SC, QD) + ETX-312, 5 mg/kg (SC, QW), 7) Vehicle (per os (PO), QD), 8) HU6, 5 mg/kg (PO, QD), 9) Resmetirom, 3 mg/kg (PO, QD), 10) Resmetirom, 3 mg/kg (PO, QD) + ETX-312, 5 mg/kg (SC, QW). Body weight was recorded daily and food intake recorded once weekly for 24 hours during the study period. The body composition of mice was be assessed by an EchoMRI 3-1 Body composition analyzer (EchoMRI, US) at week 12. Non-anaesthetised animals were placed in a plastic tube inside the MRI scanner for approximately 80 seconds. The body composition was expressed as fat mass, fat free mass (lean mass) and water. Water is normally excluded. At the end of the study period, preterminal tail vein blood collection was conducted for non- fasting plasma Alanine transaminase (ALT), Aspartate transaminase (AST), Triglycerides (TG) and Total Cholesterol (TC) analysis. Tail-vein, tongue or cheek blood was collected in heparinized tubes and mixed by inversion 5 times. Blood was placed at 4°C until it was centrifuged at 3000 g for 10 minutes. The plasma supernatants were transferred to new tubes and immediately frozen on dry ice. The samples were stored at -70°. Terminal plasma samples were prepared during anesthesia with isoflurane with the abdominal cavity opened and cardiac blood drawn with a syringe into a Microvette/Vacuette of appropriate dimensions with anticoagulant and mixed by inversion 5 times. Blood was placed at 4°C until it was centrifuged at 3000 g for 10 minutes. The plasma supernatants were transferred to new tubes and immediately frozen on dry ice. The samples were stored at -70°C. ALT, AST, TG, and TC assays were measured using commercial kits (Roche Diagnostics), on the Cobas c 501 autoanalyzer. Insulin was measured in plasma collected in heparinized tubes using the commercial MSD platform (Meso Scale Diagnostics). TIMP -1 was measured in plasma collected in EDTA tubes using a commercial ELISA kit (R&D Systems). PIIINP was measured in plasma collected in EDTA tubes using a commercial ELISA kit (Cusabio). After study termination, the liver was collected and weighed. Terminal adipose tissue weight was also measured. Specific liver samples and biopsies were dissected and prepared as follows. The liver was divided into a left lateral lobe, medial lobe, right lateral lobe, and caudate lobe. The Post-biopsy piece (~200 mg, less than 0.7 x 0.5 cm) was cut from the left lateral lobe, 4 mm from the prebiopsy site with an edge. The tissue was collected in 10% neutral buffered formalin. A liver sample collected for future analysis of mRNA expression (~150 mg) was dissected from the left medial lobe, collected in tubes and frozen in liquid nitrogen. The samples was stored at - 70°C. A second piece of liver was dissected from the center of the left lateral lobe, put in a tube and frozen in liquid nitrogen for future analysis. The samples were stored at -70°C. Data were analysed via fitting of a simple linear model with fitted coefficients for the mean effect of the treatment on the biomarker, compared to a baseline comparator. p-values correspond to one-tailed t-tests on the regression coefficients, testing the alternate hypothesis that the coefficient in question is less than 01 (one-tailed) for non-control groups (equivalent to testing there being a reductive effect versus the comparator). Where significant heteroskedasticity was observed between treatment groups, p-values were calculated using robust estimation to the variance-covariance matrix. p-values were subsequently corrected for multiple comparisons via the FDR method. FFPE biopsies were placed in 10% neutral buffered formalin (10% NBF) for approximately 24 hours and then transferred to 70% ethanol and stored at 4°C. The FFPE biopsies were then placed in the Histokinette to infiltrate prior to embedding in blocks. Biopsy tissues were cut at 3µm on a microtome and the sections were mounted on Superfrost Plus slides and stored at 4 ⁰C. Glass slides with paraffin embedded sections were deparaffinated in xylene and rehydrated in series of graded ethanol. For Hematoxylin & Eosin (H&E) staining, slides are incubated in Mayer’s Hematoxylin (Dako), washed in tap water, stained in Eosin Y solution (Sigma-Aldrich), dehydrated in graded ethanol and cover slipped. For Picrosirius red (PSR) staining, slides were incubated in Weigert’s iron hematoxylin (Sigma-Aldrich), washed in tap water, stained in Picrosirius red (Sigma-Aldrich) and washed twice in acidified water. Excess water was removed by shaking the slides and the slides were then dehydrated in three changes of 100% ethanol, cleared in xylene and cover slipped. Immunohistochemistry (IHC) was performed using standard procedures. Briefly, after antigen retrieval and blocking of endogenous peroxidase activity, slides were incubated with primary antibody. The primary antibody was detected using a polymeric HRP-linker antibody conjugate. Next, the primary antibody was visualized with DAB as chromogen. Finally, sections were counterstained in hematoxylin and cover slipped. Slides were scanned under a 20x objective in a ScanScope AT slide scanner (Aperio). Antibodies Used: Antigen Primary Antibody Vendor Col1a1 Goat anti-type I Collagen Southern Biotech, Cat.1310-01 Galectin-3 (mouse) Rat anti-Galectin 3 Biolegend, Cat.125402 α-SMA Rabbit anti-alpha smooth Abcam, Cat. ab124964 muscle actin [EPR5368] Liver samples stained with H&E or PSR were given a score for NAFLD Activity Score (NAS) and fibrosis stage, respectively, using the clinical criteria outlined by Kleiner et al. (Design and validation of a histological scoring system for nonalcoholic fatty liver disease, Hepatology, 2005) shown in the table below. Total NAS represents the sum of scores for steatosis, inflammation, and ballooning, and ranges from 0-8. NAS and fibrosis stage was determined by Gubra Histopathological Objective Scoring Technology (GHOST) deep learning app developed by Gubra using the VIS software (Visiopharm, Denmark) for a more accurate and objective method for staging disease in DIO-NASH mouse models. The app scores were reviewed by a histopathologist blinded to the results. Terminal liver biopsy histomorphometric analysis was also conducted by immunohistochemistry (IHC) for inflammation (Gal-3), Collagen (Col1a1), and activated stellate cells (a-SMA). NAS Scoring: Feature Degree Score Steatosis (percentage of <5% 0 hepatocytes with lipid droplets) 5-33% 1 >33-66% 2 >66% 3 Lobular inflammation No foci 0 <2 foci/200x 1 2-4 foci/200x 2 >4 foci/200x 3 Ballooning degeneration None 0 Few 1 Many cells/prominent 2 ballooning Fibrosis stage None 0 Perisinusoidal or periportal 1 Perisinusoidal and 2 portal/periportal 3 Bridging fibrosis 4 Cirrhosis As shown in Figure 11, the inhibitor ETX-312 resulted in a significant improvement of the NAFLD activity score (NAS). Of note, the effect obtained with ETX-312 was greater than the effects obtained with both positive controls, i.e., the GLP-1 agonist semaglutide and the THR- beta agonist resmetirom. Surprisingly, the most significant improvement was obtained when ETX-312 was combined with semaglutide or resmetirom. The impact of the inhibitor ETX-312 on the blood markers ALT, AST, TIMP-1 and PIIINP is shown in Figures 12 and 13. The terminal liver weight to body weight ratio in DIO-NASH mice that received different treatments is shown in Figure 14. The present invention is not intended to be limited in scope to the particular disclosed embodiments, which are provided, for example, to illustrate various aspects of the invention. Various modifications to the compositions and methods described will become apparent from the description and teachings herein. Such variations may be practiced without departing from the true scope and spirit of the disclosure and are intended to fall within the scope of the present disclosure.

Claims

New PCT Patent Application Based on EP 23155094.8 e-therapeutics plc Voss.-Ref.: AG1023 PCT BS CLAIMS 1. An inhibitor of expression and / or function of SLC25A5/ANT2, wherein said inhibitor is conjugated to one or more ligand moieties, preferably wherein the ligand moiety allows targeting of hepatocytes.

2. An inhibitor according to claim 1, wherein said inhibitor is an siRNA oligomer.

3. An inhibitor of expression and / or function of SLC25A5/ANT2, wherein said inhibitor is an siRNA oligomer.

4. An inhibitor according to claim 3, wherein said inhibitor comprises an siRNA oligomer conjugated to one or more ligand moieties, preferably wherein the ligand moiety allows targeting of hepatocytes.

5. An inhibitor according to claim 1, 2 or 4, wherein said one or more ligand moieties comprise one or more GalNAc ligands or comprise one more GalNAc ligand derivatives.

6. An inhibitor according to claim 1, 2 or 4 wherein said one or more ligand moieties comprise one or more GalNAc ligand derivatives.

7. An inhibitor according to one or more preceding claims, wherein the target of the inhibitor is SLC25A5/ANT2.

8. An inhibitor according to one or more preceding claims, wherein the inhibitor is a nucleic acid for inhibiting expression of SLC25A5 comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand sequences as listed in Table 2.

9. An inhibitor according to one or more preceding claims, wherein the inhibitor is a nucleic acid for inhibiting expression of SLC25A5 comprising a duplex region that comprises a first strand and a second strand that is at least partially complementary to the first strand, wherein said first strand is: (i) at least partially complementary to a portion of RNA transcribed from the SLC25A5 gene, and (ii) comprises at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the first strand modified sequences as listed in Table 3.

10. An inhibitor according claim 8 or 9, wherein the first strand comprises nucleosides 2-18 of any one of the sequences defined in claim 8 or 9, in particular wherein the first strand comprises nucleosides 2-18 of any one of the sequences defined in Tables 2 or 3.

11. An inhibitor according to claim 8, wherein the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the second strand sequences as listed in Table 2, and wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand.

12. An inhibitor according to claim 9, wherein the second strand comprises a nucleoside sequence of at least 17 contiguous nucleosides differing by 0 or 1 nucleosides from any one of the second strand modified sequences as listed in Table 4, and wherein the second strand has a region of at least 85% complementarity over the 17 contiguous nucleosides to the first strand.

13. An inhibitor according to claim 8, wherein the first strand comprises any one of the first strand sequences as listed in Table 2.

14. An inhibitor according to claim 9, wherein the first strand comprises any one of the first strand modified sequences as listed in Table 3.

15. An inhibitor according to claim 11, wherein the second strand comprises any one of the second strand sequences as listed in Table 2.

16. An inhibitor according to claim 12, wherein the second strand comprises any one of the first strand modified sequences as listed in Table 4.

17. An inhibitor according to claim 13, wherein the first strand comprises any one of the following sequences: SEQ ID NO: 304, SEQ ID NO: 323, SEQ ID NO: 439, SEQ ID NO: 453 and SEQ ID NO: 496.

18. An inhibitor according to claim 14, wherein the first strand comprises any one of the following sequences: SEQ ID NO: 856, SEQ ID NO: 875, SEQ ID NO: 991, SEQ ID NO: 1005 and SEQ ID NO: 1048.

19. An inhibitor according to claim 15, wherein the second strand comprises any one of the following sequences: SEQ ID NO:580, SEQ ID NO:599, SEQ ID NO:715, SEQ ID NO:729 and SEQ ID NO:772.

20. An inhibitor according to claim 16, wherein the second strand comprises any one of the following sequences: SEQ ID NO:1132, SEQ ID NO:1151, SEQ ID NO:1267, SEQ ID NO:1281 and SEQ ID NO:1324.

21. An inhibitor according any one of claims 8 and 11, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 304 SEQ ID NO: 580 SEQ ID NO: 323 SEQ ID NO: 599 SEQ ID NO: 439 SEQ ID NO: 715 SEQ ID NO: 453 SEQ ID NO: 729 SEQ ID NO: 496 SEQ ID NO: 772

22. An inhibitor according any one of claims 9 and 12, comprising first and second strands that comprise, consist of, or consist essentially of a nucleoside sequence differing by 0 or 1 nucleosides from any one of the following combinations of first and second sequences: Unmodified first strand Unmodified second strand SEQ ID NO: 856 SEQ ID NO: 1132 SEQ ID NO: 875 SEQ ID NO: 1151 SEQ ID NO: 991 SEQ ID NO: 1267 SEQ ID NO: 1005 SEQ ID NO: 1281 SEQ ID NO: 1048 SEQ ID NO: 1324

23. An inhibitor according any one of claims 8 to 22, wherein the first strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 23 nucleosides.

24. An inhibitor according any one of claims 8 to 23, wherein the second strand has a length in the range of 17 to 30 nucleosides, preferably 19 to 25 nucleosides, more preferably 19 or 21 or 23 nucleosides.

25. An inhibitor according any one of claims 8 to 24, wherein the duplex region of the nucleic acid is between 17 and 30 nucleosides in length, more preferably is 19 or 21 or 23 nucleosides in length.

26. An inhibitor according any one of claims 8 to 25, wherein the region of complementarity between the first strand and the portion of RNA transcribed from the SLC25A5 gene is between 17 and 30 nucleosides in length.

27. An inhibitor according any one of claims 8 to 26, wherein the nucleic acid further comprises one or more single-stranded nucleoside overhangs, optionally wherein the overhang is present on the first or second strand, preferably at the 3’ terminus of the first or second strand, and/or wherein the overhang comprises 1 to 4 nucleosides, more preferably 2 nucleosides.

28. An inhibitor according any one of claims 8 to 27, wherein the nucleic acid is an siRNA oligonucleoside.

29. An inhibitor according to any one of claims 8 to 28, wherein the second sense strand further comprises one or more abasic nucleosides in a terminal region of the second strand, and wherein said abasic nucleoside(s) is / are connected to an adjacent nucleoside through a reversed internucleoside linkage.

30. An inhibitor according to any one of claims 8 to 29, wherein the second strand comprises 2 consecutive abasic nucleosides in the 5’ terminal region of the second strand, wherein one such abasic nucleoside is a terminal nucleoside at the 5’ terminal region of the second strand and the other abasic nucleoside is a penultimate nucleoside at the 5’ terminal region of the second strand, wherein: (a) said penultimate abasic nucleoside is connected to an adjacent first basic nucleoside in an adjacent 5’ near terminal region through a reversed internucleoside linkage; and (b) the reversed linkage is a 5-5’ reversed linkage; and (c) the linkage between the terminal and penultimate abasic nucleosides is 3’5’ when reading towards the terminus comprising the terminal and penultimate abasic nucleosides.12. An inhibitor, or inhibitor for use, according claim 10 or 11, wherein the reversed internucleoside linkage is at a terminal region which is distal to the 5’ terminal region of the second strand, or at a terminal region which is distal to the 3’ terminal region of the second strand.

31. An inhibitor according to claim 30, wherein (i) the first strand and the second strand each has a length of 23 nucleosides; (ii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in said 5’ near terminal region of the second strand, wherein a first phosphorothioate internucleoside linkage is present between said adjacent first basic nucleoside of (a) and an adjacent second basic nucleoside in said 5’ near terminal region of the second strand, and a second phosphorothioate internucleoside linkage is present between said adjacent second basic nucleoside and an adjacent third basic nucleoside in said 5’ near terminal region of the second strand; (iii) two phosphorothioate internucleoside linkages are respectively between three consecutive positions in both 5’ and 3’ terminal regions of the first strand, whereby a terminal nucleoside respectively at each of the 5’ and 3’ terminal regions of said first strand is each attached to a respective 5’ and 3’ adjacent penultimate nucleoside by a phosphorothioate internucleoside linkage, and each first 5’ and 3’ penultimate nucleoside is attached to a respective 5’ and 3’ adjacent antepenultimate nucleoside by a phosphorothioate internucleoside linkage; and (iv) the second strand of the nucleic acid is conjugated directly or indirectly to one or more ligand moieties at the 3’ terminal region of the second strand.

32. An inhibitor according to claim 30 or 31, wherein, wherein the 2 consecutive inverted abasic nucleosides in the 5’ terminal region of the second strand present as the following 5’ terminal motif

wherein: T represents a 2’Me ribose modification, B represents the nucleoside bases of the first two basic nucleosides in the 5' terminal region of the second strand, and Z represents the remaining 19 contiguous basic nucleosides of said second strand.

33. An inhibitor according to any one of claims 8 to 32, wherein the nucleic acid is conjugated directly or indirectly to one or more ligand moieties, optionally wherein said ligand moiety is present at a terminal region of the second strand, preferably at the 3’ terminal region thereof.

34. An inhibitor according to claim 33, wherein the ligand moiety comprises: (i) one or more N-acetyl galactosamine (GalNAc) ligands, and / or (ii) one or more N-acetyl galactosamine (GalNAc) ligand derivatives.

35. An inhibitor according to claim 34, wherein said one or more GalNAc ligands and / or GalNAc ligand derivatives are conjugated directly or indirectly to the 5’ or 3’ terminal region of the second strand of the nucleic acid, preferably at the 3’ terminal region thereof.

36. An inhibitor according to any one of claims 33 to 35, comprising the structure:

wherein: R₁ at each occurrence is independently selected from the group consisting of hydrogen, methyl and ethyl; R2 is selected from the group consisting of hydrogen, hydroxy, -OC1-3alkyl, -C(=O)OC1- 3alkyl, halo and nitro; X1 and X2 at each occurrence are independently selected from the group consisting of methylene, oxygen and sulfur; m is an integer of from 1 to 6; n is an integer of from 1 to 10; q, r, s, t, v are independently integers from 0 to 4, with the proviso that: (i) q and r cannot both be 0 at the same time; and (ii) s, t and v cannot all be 0 at the same time; Z is an oligonucleoside moiety.

37. An inhibitor according to claim 36, comprising the structure

, wherein oligonucleotide represents the contiguous nucleosides of the second strand.

38. An inhibitor according to any one of claims 33 to 35, comprising the structure: wherein: r and s are independently an integer selected from 1 to 16; and Z is an oligonucleoside moiety.

39. An inhibitor according to claim 38, comprising the structure

40. An inhibitor according to any one of claims 37 or 39, wherein the structure is conjugated to the 3’ terminal region of the second strand.

41. An inhibitor according to any one of claims 22, 32, 37 and 40.

42. An inhibitor according to any one of claims 22, 32, 39 and 40.

43. An inhibitor according to one or more preceding claims, formulated as a pharmaceutical composition with an excipient and / or carrier.

44. A pharmaceutical composition comprising an inhibitor according to one or more preceding claims, in combination with a pharmaceutically acceptable excipient or carrier.

45. An inhibitor according to any one of claims 1 to 43 or a pharmaceutical composition according to claim 44, for use in therapy.

46. An inhibitor according to any one of claims 1 to 43 or a pharmaceutical composition according to claim 44, for use in prevention and/or treatment of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or for use in reducing adipogenesis.

47. Use of SLC25A5/ANT2 as a target for identifying one or more therapeutic agents for the prevention and/or treatment of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or for reducing adipogenesis.

48. A method of treating or preventing a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD), and/or obesity and/or a disease or disorder associated with adipogenesis and/or a method of reducing adipogenesis, which comprises administering to a patient an inhibitor of SLC25A5/ANT2, such as an inhibitor as defined according to any one of claims 1 to 43, or a pharmaceutical composition comprising an inhibitor of SLC25A5/ANT2, such as a composition as defined according to claim 44.

49. Use of an inhibitor according to any one of claims 1 to 43 or a pharmaceutical composition according to claim 44, in the preparation of a medicament for the treatment of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non- alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis and/or for reducing adipogenesis.

50. SLC25A5/ANT2 for use as a biomarker of a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis.

51. SLC25A5/ANT2 for use in an in vivo method of predicting susceptibility to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis, typically by monitoring the sequence and/ or level of expression and / or function of SLC25A5/ANT2 in a sample obtained from a patient. 53. A method of predicting susceptibility to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis, and optionally treating said metabolic disease or disorder, in a patient, said method comprising: (a) obtaining a sample from the patient, (b) detecting the sequence and / or expression and / or function of SLC25A5/ANT2 in said sample obtained from the patient, (c) predicting susceptibility to a metabolic disease or disorder, such as a metabolic disease or disorder associated with non-alcoholic fatty liver disease (NAFLD) and/or obesity and/or a disease or disorder associated with adipogenesis, based on the sequence and / or expression and / or function of SLC25A5/ANT2 in said sample obtained from the patient, (d) preferably administering to the diagnosed patient an effective amount of an inhibitor of SLC25A5/ANT2, preferably an inhibitor of SLC25A5/ANT2 according to any one of claims 1 to 43, or of a pharmaceutical composition comprising an inhibitor of SLC25A5/ANT2, such as a composition as defined according to claim 44.