RNAi AGENTS TARGETING TRANSFERRIN RECEPTOR 2 (TFR2)

Abstract

The present disclosure relates to, inter alia, compositions and methods, including ribonucleic acid interference agent (RNAi agents) agents that find use, inter alia, in the treatment management of diseases, including anemia.

Description

Attorney Docket No.: CTY-003PC / 139872-5003RNAi AGENTS TARGETING TRANSFERRIN RECEPTOR 2 (TFR2)TECHNICAL FIELDThe present disclosure relates to, inter alia, compositions and methods, including RNA interference (RNAi) agents that find use, inter alia, in the treatment management of diseases, including anemia.PRIORITYThis Application claims the benefit of, and priority to, US Application Nos. 63 / 774,414, filed March 19, 2025; 63 / 978,651, filed February 9, 2026; and 64 / 004,739, filed March 13, 2026, each of which is hereby incorporated by reference in its entirety.SEQUENCE LISTINGThe instant application contains a sequence listing, which has been submitted in XML format via Patent Center. The contents of the XML copy named “CTY-003PC_139872-5003_Sequence_Listing,” which was created on March 19, 2026, and is 1,857,468 bytes in size, are incorporated herein by reference in their entirety.BACKGROUNDAnemia of inflammation, also called anemia of chronic disease (ACD), is a type of anemia that affects people who are undergoing inflammation caused by conditions such as chronic infections, autoimmune diseases (e.g., rheumatoid arthritis and lupus), inflammatory bowel diseases (e.g., Crohn’s Disease and ulcerative colitis), cancer, chronic kidney disease (CKD), congestive heart failure, chronic pulmonary diseases, and obesity. Anemia of inflammation is the second most common type of anemia, after iron-deficiency anemia, amounting to about 40% of all anemias. See, e.g., Weiss et al., Anemia of inflammation, Blood 133(1): 40- 50 (2018). Patients suffering from anemia of inflammation have a normal or sometimes increased amount of iron stored in the body tissues, but a low level of iron in the blood. It is believed that the expression of hepcidin, the master regulator of iron homeostasis, is increased during inflammation, leading to a reduction in iron export from hepatocytes via ferroportin. In addition, shortened erythrocyte half-life, suppressed erythropoietin response to anemia, and inhibition of erythroid cell differentiation by inflammatory mediators further contribute to the pathology of anemia of inflammation. Thus, in addition to the symptoms of the underlying condition, the patients also suffers from anemia specific symptoms such as fatigue and weakness, shortness of breath, irregular heartbeat / arrhythmia / heart failure, and multi-organ failure.DB1 / 167456146.4 1Attorney Docket No.: CTY-003PC / 139872-5003Current standard of care includes treating the underlying condition and treating the anemia with agents such as erythropoiesis-stimulating agents (ESAs), which have serious side effects including increased risk of heart attack, heart failure, or stroke. As a result, a lot of patients are untreated. Therefore, there is a need for new therapies.SUMMARYAccordingly, in various aspects, the present disclosure provides RNA interference (RNAi) compositions and methods that are useful, inter alia, in reducing the levels of Transferrin receptor 2 (TFR2).In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a region of complementarity which comprises at least 12, or at least 13, or at least 14 contiguous nucleotides differing by no more than 3 nucleotides from a nucleotide sequence selected from any one of the antisense strands listed in Table 2, Table 1, Table 3, Table 4, Table 5, orTable 6, optionally wherein the RNAi agent comprises at least one chemical modification selected from internucleotide linkage modification, sugar modifications, base modifications, 5’-end modification, reversible modification, and a combination thereof.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, wherein said sense strand and said antisense strand comprises a region of complementarity which comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from any one of the duplexes listed in Table 2, Table 1, Table 3, Table 4, Table 5, or Table 6, optionally wherein the RNAi agent comprises at least one chemical modification selected from internucleotide linkage modification, sugar modifications, base modifications, 5’- end modification, reversible modification, and a combination thereof.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of SEQ ID NOs: 1-338. In embodiments, said antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 323), Duplex4181UM (SEQ ID NO: 326), Duplex4128UM (SEQ ID NO: 310), Duplex4026UM (SEQ ID NO: 275), Duplex3336UM (SEQ ID NO: 29), Duplex4125UM (SEQ ID NO: 307), and Duplex3391UM (SEQ ID NO: 53).DB1 / 167456146.4 2Attorney Docket No.: CTY-003PC / 139872-5003In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, wherein said sense strand comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of SEQ ID NOs: 339-676; and wherein said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of SEQ ID NOs: 323, 326, 310, 308, 29, 307, and 53, and 1- 338. In embodiments, the sense strand comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 661), Duplex4181UM (SEQ ID NO: 664), Duplex4128UM (SEQ ID NO: 648), Duplex4026UM (SEQ ID NO: 613), Duplex3336UM (SEQ ID NO: 367), Duplex4125UM (SEQ ID NO: 645), and Duplex3391 UM (SEQ ID NO: 391). In embodiments, the sense strand includes at least 13 contiguous nucleotides differing by no more than 3 nucleotides from any one of the respective sense strands of duplexes Duplex4178UM, Duplex4181 UM, Duplex4128UM, Duplex4026UM, Duplex3336UM, Duplex4125UM, and Duplex3391UM; SEQ ID NOs: 323, 326, 310, 308, 29, 307, and 53, and 1-338, respectively. In embodiments, the sense strand includes at least 14 contiguous nucleotides differing by no more than 3 nucleotides from any one of the respective sense strands of duplexes Duplex4178UM, Duplex4181 UM, Duplex4128UM, Duplex4026UM, Duplex3336UM, Duplex4125UM, and Duplex3391 UM; SEQ ID NOs: 323, 326, 310, 308, 29, 307, and 53, and 1-338, respectively. In embodiments, the sense strand includes at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the respective sense strands of duplexes Duplex4178UM, Duplex4181 UM, Duplex4128UM, Duplex4026UM, Duplex3336UM, Duplex4125UM, and Duplex3391UM; SEQ ID NOs: 323, 326, 310, 308, 29, 307, and 53, and 1-338, respectively. Optionally, the stretch of contiguous nucleotides of the sense strand differs by no more than two nucleotides, optionally by no more than one nucleotide, or optionally has no mismatches with any one of the respective sense strands of such duplexes.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, wherein said antisense strand comprises a region of complementarity which comprises at least 12, or at least 13, or at least 14 contiguous nucleotides differing by no more than 3 nucleotides from any one of the duplexes listed in Table 1 (one of SEQ ID NOs: 339-676 and one of 1-338, respectively). In embodiments, the sense strand and the antisense strand comprises at least 12, or at least 13, or at least 14 contiguous nucleotides differing by no more than 3 nucleotides from anyone of Duplex4178UM (SEQ ID NOs: 323 and 661), Duplex4181 UM (SEQ ID NOs: 326 and 664), Duplex4128UM (SEQ ID NOs: 310 and 648), Duplex4026UM (SEQ ID NOs: 275 and 613), Duplex3336UM (SEQ ID NOs: 29 and 367), Duplex4125UM (SEQ ID NOs: 307 and 645), andDB1 / 167456146.4 3Attorney Docket No.: CTY-003PC / 139872-5003Duplex3391 UM (SEQ ID NOs: 53 and 391), optionally wherein the sense strand and / or the antisense strand comprise at least one nucleotide modification selected from sugar modifications, internucleotide linkage modification (i.e., backbone modifications), nucleobase modifications, 5’-end modification, 3’-end modification, conjugation with a targeting moiety and a combination thereof.In embodiments, at least one of the sense strand and the antisense strand comprises a targeting ligand. In embodiments, the targeting ligand targets a receptor which mediates delivery to liver tissue.In embodiments, the targeting ligand enhances hepatocyte cell delivery of the RNAi agent compared to the delivery in the absence of the targeting ligand.In embodiments, the targeting ligand binds the Asialoglycoprotein receptor (ASGPR) on hepatocyte cells. In embodiments, the targeting ligand is selected from a GalNAc moiety, a galactosylated cholesterol, a glycolipid, an arabinogalactan (AG), bicyclic bridged ketal, and lactosylated / galactosylated moiety.In embodiments, the targeting ligand is one or more GalNAc moieties attached through a bivalent or trivalent branched linker.In embodiments, the ligand is attached to the 3’ end, the 5’ end, or the 3’ and 5’ end of the sense strand. In embodiments, the targeting ligand is a triantennary GalNAc ligand.In embodiments, the targeting ligand is attached to the RNAi agent at the 3’-terminal nucleotide residue of the sense strand.In embodiments, the targeting ligand comprises the structureDB1 / 167456146.4 4Attorney Docket No.: CTY-003PC / 139872-5003OH / OHAcHNDB1 / 167456146.4 5Attorney Docket No.: CTY-003PC / 139872-5003O~-P~~N(iPr}2O-CNEtODMTOACZDACO( (nB —,—OTMTo,„v. A, / \ / A-; HNH(f V-. / X.v'PO--CNE1DB1 / 167456146.4 6Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the targeting ligand is conjugated via a bio-cleavable linker selected from DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NOs: 339-676, wherein a substitution of a uracil for any thymine in SEQ ID NOs: 339-676 does not count as a difference that contributes to said differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NOs: 339-676; and wherein said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of 1-338, respectively, wherein a substitution of a uracil for any thymine in 1-338 does not count as a difference that contributes to said differing by no more than 3 nucleotides from any one of the nucleotide sequences of 1-338, respectively, wherein at least one of said sense strand and said antisenseDB1 / 167456146.4 7Attorney Docket No.: CTY-003PC / 139872-5003strand comprises one or more tris(GalNAc) moieties conjugated to one or more terminal nucleotide position, optionally via a linker or carrier. In embodiments, the sense strand comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 661), Duplex4181UM (SEQ ID NO: 664), Duplex4128UM (SEQ ID NO: 648), Duplex4026UM (SEQ ID NO: 613), Duplex3336UM (SEQ ID NO: 367), Duplex4125UM (SEQ ID NO: 645), and Duplex3391UM (SEQ ID NO: 391). In embodiments, said antisense strand comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from any one of SEQ ID NOs: 323, 326, 310, 308, 29, 307, and 53.In embodiments, the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of the sense strand nucleotide sequence of a duplex selected from Duplex4178UM (SEQ ID NOs: 323 and 661), Duplex4181 UM (SEQ ID NOs: 326 and 664), Duplex4128UM (SEQ ID NOs: 310 and 648), Duplex4026UM (SEQ ID NOs: 275 and 613), Duplex3336UM (SEQ ID NOs: 29 and 367), Duplex4125UM (SEQ ID NOs: 307 and 645), and Duplex3391UM (SEQ ID NOs: 53 and 391). In embodiments, the sense strand and / or the antisense strand comprise at least one nucleotide modification selected from sugar modifications, internucleotide linkage modification (i.e., backbone modifications), nucleobase modifications, 5’-end modification (without limitation, e.g., an unpaired vinyl phosphate-modified U nucleotide (vinu), positioned at the 5’-terminus of the antisense strand), 3'-end modification, conjugation with a targeting moiety (without limitation, e.g., a GalNAc moiety of any of the herein disclosed embodiments) and a combination thereof.In embodiments, the sense strand and / or the antisense strand comprise at least one nucleotide modification selected from sugar modifications, internucleotide linkage modification (i.e., backbone modifications), nucleobase modifications, 5’-end modification (without limitation, e.g., an unpaired vinyl phosphate-modified U nucleotide (vinu), positioned at the 5’-terminus of the antisense strand), 3’-end modification, conjugation with a targeting moiety (without limitation, e.g., a GalNAc moiety of any of the herein disclosed embodiments) and a combination thereof.In embodiments, the double stranded RNAi agent comprises at least one modified nucleotide.In embodiments, at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the sense strand are modified nucleotides.In embodiments, all of the nucleotides of the sense strand are modified nucleotides.DB1 / 167456146.4 8Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the antisense strand are modified nucleotides.In embodiments, all of the nucleotides of the sense strand are modified nucleotides.In embodiments, all of the nucleotides of the antisense strand are modified nucleotides.In embodiments, all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides.In embodiments, at least one of the modified nucleotides is selected from a deoxy-nucleotide, a 3’ -terminal deoxy-thymine (dT) nucleotide, a 2’-O-methyl modified nucleotide, a 2 -fluoro modified nucleotide, a 2’-deoxy- modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a T-amino-modified nucleotide, a 2’-O-allyl-modified nucleotide, 2’-C-alkyl-modified nucleotide, 2’-hydroxyl-modified nucleotide, a 2’-methoxyethyl modified nucleotide, a 2’-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5-anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a 2’-deoxy-2’-fluoro modified nucleotide, a 2’-deoxy modified nucleotide, 3’-terminal deoxy-thymine nucleotides (dT), a locked nucleotide, an abasic nucleotide, a 2'-amino-modified nucleotide, a 2’-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a nucleotide comprising a 5’-phosphorothioate group, a nucleotide comprising a 5’- methylphosphonate group, a nucleotide comprising a 5’ phosphate or 5’ phosphate mimic, a nucleotide comprising vinyl phosphonate, a nucleotide comprising adenosine-glycol nucleic acid (GNA), a nucleotide comprising thymidine-glycol nucleic acid (GNA) S-Isomer, a nucleotide comprising 2-hydroxymethyl- tetrahydrofurane-5-phosphate, a nucleotide comprising 2’-deoxythymidine-3’-phosphate, a nucleotide comprising T-deoxyguanosine-3’-phosphate, and a terminal nucleotide linked to a cholesteryl derivative and a dodecanoic acid bisdecylamide group.In embodiments, the modifications on the nucleotides are selected from 2’-O-methyl and 2’-fluoro modifications.In embodiments, the RNAi agent further includes at least one phosphorothioate internucleotide linkage. In embodiments, the double stranded RNAi agent comprises 6-8 phosphorothioate internucleotide linkages. In embodiments, the region of complementarity is at least 17 nucleotides in length.DB1 / 167456146.4 9Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the region of complementarity is about 19-23 nucleotides, or about 12-20 nucleotides, or about 14-19 nucleotides in length.In embodiments, the region of complementarity is about 14-19 nucleotides in length.In embodiments, each strand is no more than about 18 nucleotides, or no more than about 22 nucleotides, or no more than about 26 nucleotides, or no more than about 30 nucleotides in length.In embodiments, at least one strand comprises a 3’ overhang of at least 1 nucleotide.In embodiments, at least one strand comprises a 3’ overhang of at least 2 nucleotides.In embodiments, the region of complementarity comprises any one of the antisense sequences in any one of SEQ ID NOs: 1-338. In embodiments, the region of complementarity comprises any one of the antisense sequences in any one of SEQ ID NOs: 1353-1690.In embodiments, the region of complementarity consists of any one of the antisense sequences in any one of SEQ ID NOs: 1-338. In embodiments, the region of complementarity consists of any one of the antisense sequences in any one of SEQ ID NOs: 1353-1690.In embodiments, the RNAi agent further includes a phosphate or phosphate mimic at the 5’-end of the antisense strand.In embodiments, the phosphate mimic is a vinyl-phosphonate 2’-OMe-nucleotide. Optionally, the phosphate mimic is a vinyl-phosphonate 2’-OMe-uracil (vinu).In embodiments, the RNAi agent comprises at least one modified nucleotide selected from a 2’-O-methyl modified nucleotide, a 2’-fluoro modified nucleotide, and a nucleotide comprising vinyl phosphonate, optionally wherein the RNAi agent comprises at least one of each of the following modifications: 2’-O-methyl modified nucleotide, a 2’-fluoro modified nucleotide, and a nucleotide comprising vinyl phosphonate.In embodiments, the RNAi agent comprises a pattern of modified nucleotides as shown in any one of SEQ ID NOs: 1015-1690.In embodiments, the double stranded region is 12-30 nucleotide pairs in length.In embodiments, the double stranded region is 17-23 nucleotide pairs in length.In embodiments, the double stranded region is 17-25 nucleotide pairs in length.In embodiments, the double stranded region is 23-27 nucleotide pairs in length.DB1 / 167456146.4 10Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the double stranded region is 19-21 nucleotide pairs in length.In embodiments, the double stranded region is 21-23 nucleotide pairs in length.In embodiments, each strand has 12-30 nucleotides.In embodiments, each strand has 19-30 nucleotides.In embodiments, the modifications on the nucleotides are selected from LNA, glycol nucleic acid (GNA), HNA, CeNA, 2’-methoxyethyl, 2’-O-alkyl, 2’-O-allyl, 2’-C- allyl, 2’-fluoro, 2’-deoxy, 2’-hydroxyl, and combinations thereof. In embodiments, the modifications on nucleotides are selected from 2’-O-methyl, 2’-fluoro, and combinations thereof.In embodiments, the modifications on the nucleotides are 2’-O-methyl or 2’ -fluoro modifications.In embodiments, the base pair at the 1 position of the 5’-end of the antisense strand of the duplex is an AU base pair.In embodiments, the sense strand has a total of 21 nucleotides and the antisense strand has a total of 23 nucleotides.In embodiments, the sense strand has a total of 19 nucleotides and the antisense strand has a total of 21 nucleotides.In embodiments, said RNAi agent is selected from the group of chemically modified RNAi agents listed in any one of SEQ ID NOs: 1015-1690.In embodiments, all of the nucleotides of said sense strand and all of the nucleotides of said antisense strand comprise a modification.In aspects, the disclosure provides a cell containing any of the aforementioned RNAi agents.In aspects, the disclosure provides a pharmaceutical composition for reducing or suppressing expression of a TFR2 gene compared to a pretreatment control or vehicle only control comprising including any of the aforementioned RNAi agents.In aspects, the disclosure provides a pharmaceutical composition comprising a double stranded ribonucleic acid interference agent (RNAi agent), wherein:said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequenceDB1 / 167456146.4 11Attorney Docket No.: CTY-003PC / 139872-5003(vinu)sllfsuaaCfcGfAfcaguAfuGfaccsgsu (SEQ ID NO: 1675), and a sense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence gsgsucAfuAfCfUfgucgguuaaa (SEQ ID NO: 1337);said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence (vinu)sUfsuaaccgacaguAfugaccsgsu (SEQ ID NO: 1723), and a sense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence gsgsucauAfCfllfgucgguuaa (SEQ ID NO: 1703);said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence (vinu)sCfsagaAfgUfUfguuallfcAfaugsusu (SEQ ID NO: 1662), and a sense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence csasuuGfallfAfAfcaacuucuga (SEQ ID NO: 1324);said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence (vinu)sUfsgauUfaAfCfcgacAfgUfaugsasc (SEQ ID NO: 1678), and a sense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence csasuaCfuGfUfCfgguuaaucaa (SEQ ID NO: 1340); orsaid RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence (vinu)sUfsgauuaaccgacAfguaugsasc (SEQ ID NO: 1777), and a sense strand comprises a nucleotide sequence differing by no more than 2 nucleotides from the nucleotide sequence csasuacuGfuCfgguua(Agn)uca (SEQ ID NO: 1754)In embodiments, the RNAi agent is administered or suitable for administration in an unbuffered solution. In embodiments, said unbuffered solution is saline or water.In embodiments, said RNAi agent is administered or suitable for administration with a buffer solution. In embodiments, the pharmaceutical composition comprises the RNAi agent (free acid form) in water for injection at pH of about 7, adjusted with sodium hydroxide and / or phosphoric acid.In embodiments, said buffer solution comprises acetate, citrate, prolamine, carbonate, or phosphate or any combination thereof.DB1 / 167456146.4 12Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, said buffer solution is phosphate buffered saline (PBS).In aspects, the disclosure provides a method of reducing or suppressing expression of an Transferrin receptor 2 (TFR2) gene in a cell compared to a pre-treatment control or vehicle only control, the method including the steps of: (a) contacting the cell with any of the aforementioned RNAi agents or any of the aforementioned pharmaceutical compositions; and (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an TFR2 gene, thereby reducing or suppressing expression of the TFR2 gene in the cell.In embodiments, the cell is within a subject.In embodiments, the subject is a human.In embodiments, the subject is selected from a rhesus monkey, a cynomolgus monkey, a mouse, and a rat. In embodiments, the human subject suffers from anemia. In embodiments, the anemia is selected from anemia of inflammation, cancer-associated anemia, iron refractory iron deficiency anemia (I RIDA), and - thalassemia.In embodiments, the disease or disorder is anemia of inflammation. In embodiments, the disease or disorder is cancer-associated anemia. In embodiments, the disease or disorder is iron refractory iron deficiency anemia (IRIDA). In embodiments, the disease or disorder is p-thalassemia.In embodiments, the TFR2 expression is inhibited by at least about 30%.In aspects, the disclosure provides a method of treating a subject having a disorder that would benefit from a reduction in TFR2 expression, including the step of administering to the subject any of the aforementioned RNAi agents or any of the aforementioned pharmaceutical compositions, thereby treating said subject. In embodiments, the subject suffers from a TFR2-associated disorder.In embodiments, the subject is a human.In embodiments, the TFR2-associated disorder is anemia, anemia of inflammation, cancer-associated anemia, iron refractory iron deficiency anemia (IRIDA) or p-thalassemia.In embodiments, the TFR2 expression is inhibited by at least about 30%.In embodiments, the method further includes the step of administering an additional therapeutic agent to the subject.DB1 / 167456146.4 13Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the RNAi agent is capable of causing at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60% reduction of an TFR2 transcript compared to a pretreatment control or vehicle only control.In embodiments, the RNAi agent is administered to the subject intravenously.In embodiments, the method reduces the expression of a target gene in a liver tissue.In aspects, the disclosure provides a method of inhibiting the expression of TFR2 in a subject, the method including the step of: administering to said subject any of the aforementioned RNAi agents or any of the aforementioned pharmaceutical compositions, thereby inhibiting the expression of TFR2 in said subject. In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleobase sequences selected from SEQ ID NOs: 1- 338. In embodiments, the RNAi agent comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 323), Duplex4181UM (SEQ ID NO: 326), Duplex4128UM (SEQ ID NO: 310), Duplex4026UM (SEQ ID NO: 275), Duplex3336UM (SEQ ID NO: 29), Duplex4125UM (SEQ ID NO: 307), and Duplex3391UM (SEQ ID NO: 53).In embodiments, the RNAi agent comprises one or more modifications selected from a 2’-O-methyl modified nucleotide, a 2-fluoro modified nucleotide, a nucleotide comprising a glycol nucleic acid (GNA), a phosphorothioate (PS), a vinyl-phosphonate 2’-OMe-nucleotide (e.g, a vinyl-phosphonate 2’-OMe-uracil (vinu)), optionally wherein said RNAi agent comprises at least one of each modification selected from a 2’- O-methyl modified nucleotide, a 2’-fluoro modified nucleotide, a phosphorothioate and a vinyl-phosphonate 2’-OMe-uracil (vinu).In embodiments, the RNAi agent comprises four or more PS modifications, optionally six to ten PS modifications, and optionally six PS modifications.In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, and wherein the RNAi agent comprises six PS modifications positioned at the penultimate and ultimate internucleotide linkages from the 5’ -terminus of the sense and the respective 3’- and 5’-termini of the antisense strands of the RNAi agent.DB1 / 167456146.4 14Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, and wherein the RNAi agent comprises two or more 2’-fluoro modified nucleotides, optionally wherein each of the sense strand and the antisense strand of the RNAi agent comprises two or more 2’-fluoro modified nucleotides, optionally wherein the 2’-fluoro modified nucleotides are located on the sense strand at nucleobase positions 5, 7, 8, and 9 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 2, 6, 8, 9, 14 and 16 from the 5’-terminus of the antisense strand.In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, and wherein the RNAi agent comprises two or more 2’-fluoro modified nucleotides, optionally wherein each of the sense strand and the antisense strand of the RNAi agent comprises two or more 2’-fluoro modified nucleotides, optionally wherein the 2’-fluoro modified nucleotides are located on the sense strand at nucleobase positions 7, 9, 10, and 11 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 2, 6, 8, 9, 14 and 16 from the 5’-terminus of the antisense strand.In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, and wherein the RNAi agent comprises two or more 2’-O-methyl modified nucleotides, optionally wherein each of the sense strand and the antisense strand of the RNAi agent comprises two or more 2’-O-methyl modified nucleotide nucleotides, optionally wherein the 2’-O-methyl modified nucleotide nucleotides are located on the sense strand at nucleobase positions 1, 2, 3, 4, 6, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 3, 4, 5, 7, 10, 11, 12, 13, 15, 17, 18, 19, 20, and 21 from the 5’-terminus ofthe antisense strand.In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, and wherein the RNAi agent comprises two or more 2’-O-methyl modified nucleotides, optionally wherein each of the sense strand and the antisense strand of the RNAi agent comprises two or more 2’-O-methyl modified nucleotides, optionally wherein the 2’-O-methyl modified nucleotides are located on the sense strand at nucleobase positions 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17, 18, 19, 20, and 21 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 1, 3, 4, 5, 7, 10, 11, 12, 13, 15, 17, 18, 19, 20, 21, 22, and 23 from the 5’-terminus ofthe antisense strand.DB1 / 167456146.4 15Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a3’-terminus, and wherein the RNAi agent comprises one or more vinu modifications, optionally wherein the RNAi agent comprises a single vinu modification at the 5’-terminus of the antisense strand. In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, wherein each of the sense strand and the antisense strand of the RNAi agent comprises 2’-fluoro modified nucleotides located on the sense strand at nucleobase positions 5, 7, 8, and 9 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 2, 6, 8, 9, 14 and 16 from the 5’-terminus of the antisense strand, wherein each of the sense strand and the antisense strand of the RNAi agent comprises 2’-O-methyl modified nucleotide nucleotides located on the sense strand at nucleobase positions 1, 2, 3, 4, 6, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 3, 4, 5, 7, 10, 11, 12, 13, 15, 17, 18, 19, 20, and 21 from the 5’-terminus of the antisense strand, and wherein the RNAi agent comprises a single vinu modification at the 5’-terminus of the antisense strand.In embodiments, each of the sense strand and the antisense strand of the RNAi agent comprises a 5’- terminus and a 3’-terminus, wherein each of the sense strand and the antisense strand of the RNAi agent comprises 2’-fluoro modified nucleotides located on the sense strand at nucleobase positions 7, 9, 10, and 11 from the 5’-terminus of the sense strand and on the antisense strand at nucleobase positions 2, 6, 8, 9, 14 and 16 from the 5’-terminus of the antisense strand, wherein each of the sense strand and the antisense strand of the RNAi agent comprises 2’-O-methyl modified nucleotide nucleotides located on the sense strand at nucleobase positions 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17, 18, 19, 20, and 21 from the 5’ -terminus of the sense strand and on the antisense strand at nucleobase positions 1, 3, 4, 5, 7, 10, 11, 12, 13, 15, 17, 18, 19, 20, 21, 22, and 23 from the 5’ -terminus of the antisense strand, and wherein the RNAi agent comprises a single vinu modification at the 5’ -terminus of the antisense strand.In aspects, the disclosure provides a method for treating, delaying progression of or preventing a TFR2- associated disease or disorder in a subject, the method including the step of administering to said subject any of the aforementioned RNAi agents or any of the aforementioned pharmaceutical compositions, thereby treating or preventing a TFR2-associated disease or disorder in the subject.In aspects, the disclosure provides a ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises an antisense strand, and wherein said antisense strand comprises a region of complementarity which comprises at least 12 differing by no more than 3 nucleotides from any one of SEQDB1 / 167456146.4 16Attorney Docket No.: CTY-003PC / 139872-5003ID NOs: 1-338, wherein the antisense strand is and no more than about 18 nucleotides contiguous nucleotides. In embodiments, the antisense strand has a length of 12 nucleotides, or 13 nucleotides, or 14 nucleotides, or 15 nucleotides, or 16 nucleotides, or 17 nucleotides, or 18 nucleotides. In embodiments, the antisense strand has a length of 14 nucleotides. In embodiments, said antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 323), Duplex4181 UM (SEQ ID NO: 326), Duplex4128UM (SEQ ID NO: 310), Duplex4026UM (SEQ ID NO: 275), Duplex3336UM (SEQ ID NO: 29), Duplex4125UM (SEQ ID NO: 307), and Duplex3391UM (SEQ ID NO: 53). In embodiments, said antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178 (SEQ ID NO: 1337), Duplex4181 (SEQ ID NO: 1340), Duplex4128 (SEQ ID NO: 1324), Duplex7902 (SEQ ID NO: 1703), Duplex8045 (SEQ ID NO: 1754), Duplex4026 (SEQ ID NO: 1289), Duplex3336 (SEQ ID NO: 1043), Duplex4125 (SEQ ID NO: 1321), and Duplex3391 (SEQ ID NO: 1067).In embodiments, the RNAi agent further comprising a sense strand from any one of at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of SEQ ID NOs: 339-676. In embodiments, the RNAi agent is double stranded. In embodiments, the sense strand comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178UM (SEQ ID NO: 661), Duplex4181 UM (SEQ ID NO: 664), Duplex4128UM (SEQ ID NO: 648), Duplex4026UM (SEQ ID NO: 613), Duplex3336UM (SEQ ID NO: 367), Duplex4125UM (SEQ ID NO: 645), and Duplex3391UM (SEQ ID NO: 391). In embodiments, the sense strand comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from any one of Duplex4178 (SEQ ID NO: 1675), Duplex4181 (SEQ ID NO: 1678), Duplex4128 (SEQ ID NO: 1662), Duplex7902 (SEQ ID NO: 1723); Duplex8045 (SEQ ID NO: 1777), Duplex4026 (SEQ ID NO: 1627), Duplex3336 (SEQ ID NO: 1381), Duplex4125 (SEQ ID NO: 1659), and Duplex3391 (SEQ ID NO: 1405).In embodiments, the RNAi agent comprises at least one modified nucleotide. In embodiments, at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the antisense strand are modified nucleotides. In embodiments, all of the nucleotides of the antisense strand are modified nucleotides.DB1 / 167456146.4 17Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the sense strand are modified nucleotides. In embodiments, all of the nucleotides of the sense strand are modified nucleotides.In embodiments, the modified nucleotides comprise nucleotide modifications selected from sugar modifications, internucleotide linkage modification (i.e., backbone modifications), nucleobase modifications, 5’-end modification, 3’-end modification, conjugation with a targeting moiety and a combination thereof. In embodiments, the nucleotide modifications are selected from a deoxy-nucleotide, a 3’-terminal deoxythymine (dT) nucleotide, a 2’-O-methyl modified nucleotide, a 2’-fluoro modified nucleotide, a 2’-deoxy- modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a T-amino-modified nucleotide, a 2’-O-allyl-modified nucleotide, 2’-C-alkyl-modified nucleotide, 2’-hydroxyl-modified nucleotide, a 2’-methoxyethyl modified nucleotide, a 2’-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5-anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a 2’-deoxy-2’-fluoro modified nucleotide, a 2’-deoxy modified nucleotide, 3’-terminal deoxy-thymine nucleotides (dT), a locked nucleotide, an abasic nucleotide, a 2’-amino-modified nucleotide, a 2’-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a nucleotide comprising a 5’-phosphorothioate group, a nucleotide comprising a 5’- methylphosphonate group, a nucleotide comprising a 5’ phosphate or 5’ phosphate mimic, a nucleotide comprising vinyl phosphonate, a nucleotide comprising adenosine-glycol nucleic acid (GNA), a nucleotide comprising thymidine-glycol nucleic acid (GNA) S-Isomer, a nucleotide comprising 2-hydroxymethyl- tetrahydrofurane-5-phosphate, a nucleotide comprising 2’-deoxythymidine-3’-phosphate, a nucleotide comprising T-deoxyguanosine-3’-phosphate, and a terminal nucleotide linked to a cholesteryl derivative and a dodecanoic acid bisdecylamide group. In embodiments, modifications on the nucleotides are 2’-O-methyl and 2’-fluoro modifications. In embodiments, the nucleotide modifications comprise at least one phosphorothioate internucleotide linkage.In embodiments, the RNAi agent comprises 6-8 phosphorothioate internucleotide linkages. In embodiments, the 5’ modification is or comprises a vinyl phosphonate-modified nucleotide, e.g., a vinyl-phosphonate 2’- OMe-uracil ("vinu" modification).DB1 / 167456146.4 18Attorney Docket No.: CTY-003PC / 139872-5003In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, the RNAi agent having an antisense strand complementary to at least one portion of an mRNA of transferrin receptor 2 (TFR2) and a sense strand, where: the sense strand (SS) is 19 to 25 nucleotides in length and includes a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 to 25 nucleotides in length and includes a 5'-terminus and a 3'-terminus, where the AS, starting from the 5'-terminal nucleotide as position 1, includes the following modifications: at AS position 2: a 2’-fluoro (2'-F) modification; at AS position 5: a 2'-F or 2'-deoxyribonucleotide (dN) modification; at AS position 7: a 2'- F or dN modification; at AS position 12: a 2'-F or dN modification; and at AS position 14: a 2'-F or dN modification, where the AS includes a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and where the SS, starting from the 5'-terminal nucleotide as position 1, includes a 2'-F, dN, a glycol nucleic acid (GNA), or 2'-O-methyl ribonucleotide (2'- OMe) modification at two or more positions of the that correspond to positions 7, 8, 9, and / or 15 of a 19- nucelotide SS, where the SS includes a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In embodiments, the RNAi agent further includes one or more of the following: a Tm reducing modification; a 5' AS modification that boosts RISC loading; and / or a targeting ligand. Optionally, the Tm reducing modification is a GNA at a position of the SS that corresponds to position 15 of a 19-nucleotide SS and / or the targeting ligand is a GalNAc ligand.In another embodiment, the RNAi agent further includes one or more of the following: a Tm reducing modification, a vinyl-phosphonate 2'-OMe-uracil (vinu), and / or a targeting ligand. Optionally, theTm reducing modification is a GNA. Optionally, the vinu is at position 1. Optionally, the targeting ligand includes a GalNAc moiety. Optionally, the GalNAc moiety is attached to the 3'-terminus of the SS.In embodiments, the RNAi agent includes the SS and the AS forming a duplex.In embodiments, the RNAi agent includes one or more nucleic acids of the SS and the AS being independently modified nucleic acids.In embodiments, the RNAi agent comprises one or more nucleic acid linkages of the SS and the AS that are modified nucleic acid linkages.DB1 / 167456146.4 19Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the RNAi agent further includes a 2'-0Me modification at position 3, 4, 6, 8, 9, 10, 13, 15, 16, 17, 18, 19, 20, and / or 21 of the AS.In embodiments, the RNAi agent further includes a 2'-OMe modification atposition(s) of the SS corresponding to positions 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 16, 17, 18, and / or 19 of a 19-nucleotide SS.In embodiments, the RNAi agent further includes a PS modification at one or more of the following internucleotide linkages: positions 1-2 and / or 2-3 of the SS, and / or positions 1-2, 2-3, 19-20 and / or the ultimate and / or penultimate internucleotide linkages at the 3'-end of the AS of the AS. In embodiments, the RNAi agent includes the AS further including a vinyl-phosphonate 2'-OMe-uracil (vinu) at position 1.In embodiments, a PS modification may be present at the ultimate internucleotide linkage at the 3’-end of the SS and / or at position 19 of the SS (the latter such as to provide a linkage between said position and a ligand, such as, e.g., GalNAc).In embodiments, the RNAi agent includes the AS further including a vinyl-phosphonate 2'-OMe-uracil (vinu) at position 1.In embodiments, the RNAi agent further includes an inverted abasic nucleotide ([N]) at or near the 5'-end of the SS.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.DB1 / 167456146.4 20Attorney Docket No.: CTY-003PC / 139872-5003In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 12: a 2'-F modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, at position 9: a 2'-F modification, and at position 15: a glycol nucleic acid (GNA), wherein an inverted abasic nucleotide [N] is bound with the nucleotide at position 1 of the SS, and wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 12: a dN modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length DB1 / 167456146.4 21Attorney Docket No.: CTY-003PC / 139872-5003and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815. 1817. 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339- 676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a 2'-F modification, at position 12: a 2'-F modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide DB1 / 167456146.4 22Attorney Docket No.: CTY-003PC / 139872-5003sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'- deoxyribonucleotide (dN) modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797. 1799. 1801. 1803. 1805. 1807. 1809. 1811. 1813. 1815. 1817. 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 8: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 6: a 2'-F modification, at position 8: a 2'-F modification, at position 9: a 2'-F modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 8: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has DB1 / 167456146.4 23Attorney Docket No.: CTY-003PC / 139872-5003a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, at position 9: a 2'-F modification, at position 15: a glycol nucleic acid (GNA) modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 9: a 2'-F modification, at position 15: a glycol nucleic acid (GNA) modification, wherein an inverted abasic nucleotide [N] is bound with the nucleotide at position 1 of the SS, and wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796. 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.DB1 / 167456146.4 24Attorney Docket No.: CTY-003PC / 139872-5003In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) DB1 / 167456146.4 25Attorney Docket No.: CTY-003PC / 139872-5003modification, at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 12: a 2'-F modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-F modification, at position 7: a 2'-F modification, at position 12: a 2'-F modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, DB1 / 167456146.4 26Attorney Docket No.: CTY-003PC / 139872-50031786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797. 1799. 1801. 1803. 1805. 1807. 1809. 1811. 1813. 1815. 1817. 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-deoxyribonucleotide (dN) modification, at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796. 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides andDB1 / 167456146.4 27Attorney Docket No.: CTY-003PC / 139872-5003comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 8: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815. 1817. 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 8: a DB1 / 167456146.4 28Attorney Docket No.: CTY-003PC / 139872-50032'-F modification, and at position 9: a 2'-F modification wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796. 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815. 1817. 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 9: a 2'-F modification wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792. 1794. 1796. 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824. In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819. 1821. 1823, or 1825; and wherein the SS comprises: at position 5: a 2'-F modification, at position 7: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796. 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least oneDB1 / 167456146.4 29Attorney Docket No.: CTY-003PC / 139872-5003portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-deoxyribonucleotide (dN) modification, at position 7: a dN modification, at position 12: a dN modification, and at position 14: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798. 1800. 1802. 1804. 1806. 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 5: a 2'-F modification, at position 12: a 2'-F modification, at position 14: a 2'-F modification, and at position 16: a 2'-F modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808. 1810. 1812. 1814. 1816. 1818. 1820. 1822, or 1824.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent) capable of inhibiting the expression of TFR2, comprising an antisense strand complementary to at least one portion of an mRNA of TFR2 and a sense strand, wherein: the sense strand (SS) is 19 nucleotides in length and comprises a 5'-terminus and a 3'-terminus, and the antisense strand (AS) is 21 nucleotides and comprises a 5'-terminus and a 3'-terminus, wherein the AS comprises: at position 2: a 2’-fluoro (2'-F) modification, at position 4: a 2'-F modification, at position 6: a 2'-F modification, at position 12: a 2'-F modification, at position 14: a 2'-F modification, at position 16: a 2'-F modification, and at position 18: a 2'-F DB1 / 167456146.4 30Attorney Docket No.: CTY-003PC / 139872-5003modification; and wherein the AS has a nucleotide sequence having at least 80% sequence identity to any one ofSEQ ID NOs: 1-338, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, or 1825; and wherein the SS comprises: at position 7: a 2'-F modification, at position 8: a 2'-F modification, and at position 9: a 2'-F modification, wherein the SS has a nucleotide sequence having at least 80% sequence identity to any one of SEQ ID NOs: 339-676, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, or 1824.In aspects, the disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier, and any of the aforementioned RNAi agents.In aspects, the disclosure provides a method for treating, delaying progression of or preventing a TFR2- associated disease or disorder in a subject, the method comprising administering to said subject any of the aforementioned RNAi agents or any of the any of the aforementioned pharmaceutical composition, thereby treating or preventing a TFR2-associated disease or disorder in the subject.In aspects, the disclosure provides a method for treating, delaying progression of or preventing a TFR2- associated disease or disorder in a subject, the method comprising contacting a cell derived from the subject with any of the aforementioned RNAi agents or any of the any of the aforementioned pharmaceutical composition, optionally culturing the cell in vitro and administering the cell to the subject.In embodiments, the TFR2-associated disease or disorder is the human subject suffers from is anemia. In embodiments, the human subject suffers from anemia of inflammation. In embodiments, the human subject suffers from iron refractory iron deficiency anemia (IRIDA). In embodiments, the human subject suffers from P-thalassemia.In embodiments, the method of any of the aspects or embodiments disclosed herein causes a reduction in TFR2 mRNA in the liver by at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80% or more. In embodiments, the method of any of the aspects or embodiments disclosed herein causes a reduction in TFR2 protein in the blood, plasma or serum by at least about 10%, or at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80% or more. In embodiments, the method of any of the aspects or embodiments disclosed herein causes a reduction in retinol levels in the blood, plasma or serum by at least about 10%, or at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least DB1 / 167456146.4 31Attorney Docket No.: CTY-003PC / 139872-5003about 80% or more. In embodiments, the method of any of the aspects or embodiments disclosed herein the method causes a reduction in the serum level of hepcidin or active fragments thereof by at least about 10%, or at least about 20%, or at least about 30%, or at least about 40%, or at least about 50% or more. In embodiments, the derivative of vitamin A is 11 -cis-retinal or all-trans-retinal.In aspects, the disclosure provides a kit for performing any of the aforementioned methods, including: a) the RNAi agent, and b) instructions for use, and c) optionally, a means for administering the RNAi agent to the subject.The disclosure provides RNAi agents for inhibiting TFR2. Compositions and articles defined by the disclosure were isolated or otherwise manufactured in connection with the examples provided below. Other features and advantages of the disclosure will be apparent from the detailed description, and from the claims.Any aspect or embodiment disclosed herein can be combined with any other aspect or embodiment as disclosed herein.BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a scatterplot showing the screening of 916 GalNAc-conjugated-siRNA duplexes in silencing mRNA expression of Transferrin receptor 2 (TFR2) in primary human hepatocytes (PHH) delivered at 1 pM and 0.1 pM via GalNAc-mediated free uptake. X and Y axes indicate the remaining percentage of TFR2 mRNA normalized to controls. A publicly known reference duplex is color coded.FIG.2 is a scatterplot showing the screening of 175 GalNAc-conjugated, chemically modified siRNA duplexes in silencing gene expression of TFR2 in primary cynomolgus hepatocytes (PCH) as a function of gene expression of TFR2 in primary human hepatocytes (PHH) delivered at 1 pM via GalNAc-mediated free uptake. Publicly known reference duplexes are color coded. 147 duplexes that showed <60% TFR2 mRNA remaining in PHH and <70% TFR2 mRNA remaining in PCH (including reference duplexes) are bracketed with dashed lines.FIG. 3 shows the extent of silencing of TFR2 by top 160 chemically modified siRNA duplexes transfected at 50 nM in Hep3B cells. Hep3B cells express low levels of TFR2 but the error bars show that reliable silencing results were observed.FIG. 4 is a bar graph showing the number of differentially expressed genes in Hep3B cells treated with 160 TFR2 duplexes or four controls, indicated with numerals 1-4, each at 50 nM, as determined by RNA-seq analysis.DB1 / 167456146.4 32Attorney Docket No.: CTY-003PC / 139872-5003FIG. 5 shows volcano plots of off target profiles for selected duplexes via differentially expressed genes (DEGs). X-axis represents fold change knockdown and Y-axis indicates p-value for each DEG. Sequencing analysis of the RNA was performed, and genes were considered differentially expressed if the absolute value of the Log2(Fold change)= - / - 0.58 compared to the mock-transfected controls and padj <0.05. DEGs are represented by a red dot.FIG. 6A and FIG. 6B depict representative dose response curves for 5 selected duplexes in both primary human hepatocytes (FIG. 6A) and primary cynomolgus hepatocytes (PCH, FIG.6B) after 24 hours of culture. All doses were normalized to lowest dose.FIG. 7A and FIG. 7B show the knockdown of human TFR2 protein in mice expressing AAV delivered hTFR2 after two weeks of RNAi treatment. FIG. 7A shows knockdown induced by 15 duplexes that were tested at 3 mg / kg. FIG. 7B shows knockdown induced by 5 duplexes that were tested in dose response 3, 1, 0.3 mg / kg. Knockdown is visualized as percent of vehicle-treated AAV control.FIG. 8 shows the in vivo activity of 5 duplexes dosed at 1 mg / kg and 3 mg / kg in NHP over time. The knockdown of TFR2 mRNA (top panels), the levels of serum iron (middle panels), and the transferrin saturation (TSAT) (bottom panels) are shown. Knockdown of TFR2 is plotted as % change from individual animal baseline.FIG. 9A and FIG. 9B depict the in vivo activity of Duplex4178 in NHP dosed at 1 and 3 mg / kg from 2 weeks prior to dosing to 92 days post dose. FIG. 9A shows the knockdown of TFR2 mRNA. FIG. 9B shows the levels of blood Hb (top panel), the transferrin saturation (TSAT) (middle panel) and the levels of serum iron (bottom panel).FIG. 10 shows a schematic diagram that compares exemplary herein disclosed modification patterns for 19 / 21-mer RNAi agents. Nucleotides are color coded based on chemical modification: 2'-F modifications are shown in yellow and indicated by number 1; dN modifications are shown in red and indicated by number 2; vinyl-phosphonate 2'-OMe-uracil (“vinu”) modifications are shown in blue and indicated by number 3; glycol nucleic acid (GNA) modifications are shown in purple and indicated by number 4; and 2'-OMe modifications are shown in black. Phosphorothionate linkages are shown as bridges between nucleotides and a rhombus depicts an inverted abasic modification. The sense strand (top strand) is shown in a 5’ to 3’ orientation from left to right, and the antisense strand (bottom stand) is shown in a 3’ to 5’ orientation from left to right. GalNac is indicated with a rectangle attached to the 3’ end of the sense strand. In some embodiments, theDB1 / 167456146.4 33Attorney Docket No.: CTY-003PC / 139872-5003modification patterns disclosed in FIG. 10 may have a nucleotide sequence having at least 80% sequence identity to a sequence disclosed herein in Table 5 or Table 6.FIG. 11 shows an example normalized performance of modified TFR2-targeting RNAi agents as disclosed herein relative to a parent duplex across two test concentrations (10 and 1000 nM). Each design, listed on the y-axis, incorporates distinct fluorination, deoxyribonucleotide, or GNA modification patterns, while the x- axis reports performance normalized to the parent. Colored markers denote different seed locations. Several designs outperform the parent across both concentrations, demonstrating that specific modification patterns and seed placements can substantially improve duplex activity. At the bottom is a schematic diagram of a “5F (F@ AS2 / 14, S7 / 8 / 9; dN @ AS5 / 7 / 12)” modification pattern format TFR2-targeting RNAi agent having SS SEQ ID NO: 1792 (further including a 3'-terminal GalNAc as shown) and AS SEQ ID NO: 1793. Duplexes are color- and number-coded as in FIG. 10.FIG. 12 shows an example fold-change performance of multiple TFR2-targeting RNAi agents as disclosed herein relative to a 5F-3dN reference TFR2-targeti ng RNAi agent (specifically, the “5F (F@ AS2 / 14, S7 / 8 / 9; dN @ AS5 / 7 / 12)” format RNAi agent of FIG. 11 was altered with various different modifications, as indicated, for purpose of assessing structure-activity relationships (SAR) across the RNAi agent’s modifications) at 10 nM. Each design, listed along the y-axis, incorporates distinct combinations of 2'-O-methyl, 2'-fluoro, deoxyribonucleotide, GNA, or triplet-break substitutions. The x-axis reports fold-change relative to the reference duplex, with values greater than 1 indicating improved activity. At the bottom is a schematic diagram of the “3dN to F_AS, SS1 invabasic, SS15GNA” RNAi agent having SS SEQ ID NO: 1796 (further including a 3'-terminal GalNAc as shown) and AS SEQ ID NO: 1797. Duplexes are color- and number-coded as in FIG. 10.FIG. 13 shows a schematic diagram of a “1 OF” format modification pattern on a TFR2-targeti ng RNAi agent, where SS is 5'- mGmGmUmCfAmUfAfCfUmGmUmCmGmGmUmUmAmAmA-3' (SEQ ID NOs: 1808, further including a 3'-terminal GalNAc and modifications, as shown) and AS is 5'(vinu)sUmUmAmAfCmCfGfAmCmAmGmUfAmUfGmAmCmC-3' (SEQ ID NO: 1809). Duplexes are color- and number-coded as in FIG. 10.FIG. 14 shows an example comparative plots illustrating overall Iog2 fold change in target gene knockdown relative to a parent or baseline RNA interference (RNAi) agent for a plurality of chemically modified RNAi agents across two different target mRNAs (Target 1 (Target 1 is TFR2) and Target 2), wherein each dataDB1 / 167456146.4 34Attorney Docket No.: CTY-003PC / 139872-5003point represents the median knockdown with 95% confidence intervals, and wherein marker color and marker size indicate relative sequence dependency associated with the respective modification patterns.FIG. 15 shows an example schematic and comparative analysis illustrating the effect of selected AS and SS chemical modification patterns on RNAi activity. As shown, the right of the figure depicts representative modification patterns (A, k, I, m, n, F, o, and p) highlighting positional substitution of modified nucleotides. The left portion shows fold change in gene knockdown for corresponding RNAi duplexes relative to a reference 5-fluoro, deoxyribonucleotide-containing duplex, with individual data points representing different duplex constructs evaluated under comparable conditions. Duplexes are color- and number-coded as in FIG.10.FIG. 16 shows a schematic diagram that compares additional exemplary herein disclosed modification patterns for 19 / 21-mer RNAi agents. Nucleotides are color coded based on chemical modification: 2'-F modifications are shown in yellow and indicated by number 1; dN modifications are shown in red and indicated by number 2; vinyl-phosphonate 2'-OMe-uracil (“vinu”) modifications are shown in blue and indicated by number 3; glycol nucleic acid (GNA) modifications are shown in purple and indicated by number 4; and 2'-OMe modifications are shown in black. Phosphorothionate linkages are shown as bridges between nucleotides and a rhombus depicts an inverted abasic modification. The sense strand (top strand) is shown in a 5’ to 3’ orientation from left to right, and the antisense strand (bottom stand) is shown in a 3’ to 5’ orientation from left to right. GalNac is indicated with a rectangle attached to the 3’ end of the sense strand. In some embodiments, the modification patterns disclosed in FIG.10 may have a nucleotide sequence having at least 80% sequence identity to a sequence disclosed herein in Table 5 or Table 6. A rhombus depicts an inverted abasic modification, while phosphorothionate linkages are shown as bridges between nucleotides, or between an inverted abasic nucleotide modification and an indicated 5'-terminal nucleotide, or between indicated 3'-terminal nucleotides and GalNAc modifications.DETAILED DESCRIPTIONThe present disclosure relates, at least in part, to the discovery of double stranded ribonucleic acid interference agents (RNAi agents) capable of robust inhibition of Transferrin receptor 2 (TFR2), in cells, tissues and subjects. As detailed below, TFR2 plays a critical role in regulation of iron metabolism. Via this action, TFR2 contributes to the pathology of various diseases and disorders, including, but not limited to, hematological disease and disorders such as anemia (e.g., anemia of inflammation, cancer-associatedDB1 / 167456146.4 35Attorney Docket No.: CTY-003PC / 139872-5003anemia, and iron refractory iron deficiency anemia (I RIDA)) and 0-thalassemia making it a molecular target for treating, delaying progression of or preventing these diseases.Described herein are rules of chemical modification and modification patterns made upon a variety of dsRNAs that function as RNAi triggers (RNAi agents), where such dsRNAs are capable of inhibiting expression of a target gene. Exemplary dsRNAs include, e.g., siRNAs, among other art-recognized RNAi-inducing double stranded siRNA formats.In embodiments, an RNAi agent of the disclosure has a sense strand of 19 to 25 nucleotides in length and an antisense strand of 21 to 25 nucleotides in length (the two strands thereby forming a X / Y-mer, where X and Y are the nucleotide lengths of the sense and antisense strand, respectively when annealed to one another as a dsRNA). It will be appreciated by the ordinarily skilled artisan in the relevant art that antisense strand modification patterns disclosed herein may be transferred from one length of antisense strand (AS) to another length of antisense strand by maintaining position numbers of specified modifications in reference to the 5'-terminal residue of the AS as position 1. For example, if positions 1, 2, and / or 3 of an AS of 21 nucleotides in length carry a specific type of nucleotide modification, then a preferred manner of transferring that pattern to an AS of greater or less length (e.g., nucleic acids) is to maintain those same modifications at positions 1, 2, and / or three of the AS of greater or lesser nucleic acids in length. In contrast, it will be further appreciated that for transfer of a SS modification pattern from a first SS of a certain length to a second SS of a different length, a preferred modification pattern transfer will maintain the position of such SS modifications in reference to the corresponding AS positions. Thus, for a 19 / 21 mer, in which the 19-nucleotide-long sense strand (SS) carries modifications at positions 1 or 2 of the SS, a preferred transfer of that modification pattern to a 20-nucleotide-long SS in a corresponding 20 / 22mer would involve the SS having those modifications at positions 2 or 3 of the 20-nucleotide SS, as that would maintain the relative position of such modifications in reference to the antisense strand (AS) of that double stranded RNA. More generally, while the position of modifications on the AS are maintained in moving from, e.g., a 19 / 21 mer to a 20 / 22mer (or other staggered- length duplexes), for the SS of the 19 / 21 mer modified at position n in the 19 / 21 mer, the SS of the 20 / 22mer carrying a preferred transferred modification pattern has that modification at position n + 1 of the SS of the 20 / 22mer.In embodiments, the RNAi agent sense and antisense strands are each independently 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In embodiments, a RNAi agent has a duplex length of about 19, 20, 21, 22, 23, 24 or 25 nucleotides.DB1 / 167456146.4 36Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the region of perfect or substantial complementarity between the sense strand and the antisense strand is 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.In embodiments, the sense strand and antisense strand of the RNA interference agent may anneal to form a duplex region in which the paired portion of the strands may be defined by overlap of a sense strand (SS) and an antisense strand (AS). The antisense strand duplex region sequence may be about 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100% (perfectly), or any value therebetween, complementary to a nucleotide sequence (e.g., a target sequence) present in a target mRNA. Because a duplex region may be defined by complementarity of two strands, a sense strand duplex region sequence may be partially or wholly complementary to a corresponding nucleotide sequence present in a target mRNA. A sense strand duplex region may be the same length as, or shorter than, a corresponding antisense strand duplex region.In embodiments, the sense strand (SS) and the antisense strand (AS) may anneal to form a duplex. An SS and AS may be partially, substantially, or fully complementary to one another within a complementary region, such as, e.g., with a sense-strand core-stretch sequence being at least 70%, 75%, 80%, 85%, 90%, 95%, 99%, 100%, or any value therebetween, complementary to an antisense core-stretch sequence. In embodiments, a sense-strand core-stretch sequence may include at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, or at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25 nucleotides that are at least 75% to 100% complementary to a corresponding 10-25-nucleotide portion of an antisense-strand core-stretch sequence.In embodiments, a SS or an AS may independently contain an additional 1-6 nucleotides (an overhang sequence) at a 3' end, a 5' end, or both ends of a duplex region. Any additional nucleotides present at a 3' or 5' end of a AS may or may not be complementary to a corresponding sequence in a target mRNA. Any additional nucleotides present at a terminus of a SS may or may not be identical to corresponding positions in a target mRNA. Overhangs may therefore occur on one or both strands and may be complementary, non- complementary, or mismatched.In embodiments, a duplex-paired region formed between an SS and AS may include at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, or at least 25 nucleotides. In embodiments, the duplex-paired region is 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.In embodiments, referencing sequences set forth herein, an RNAi agent may incorporate one or more alternative nucleotides (e.g., an RNA counterpart of a DNA nucleotide or a DNA counterpart of an RNA nucleotide), and / or one or more chemically modified nucleotides, and / or one or more modified internucleotide DB1 / 167456146.4 37Attorney Docket No.: CTY-003PC / 139872-5003linkages, while maintaining essentially the same complementary behavior as the corresponding sequence listing entry.In embodiments, the SS and AS may may contain one or more mismatches (e.g., 1, 2, 3, 4, or 5) relative to each other within a complementary region. Where multiple mismatches are present, such mismatches may occur consecutively (e.g., 2-3 or more in a row) or may be dispersed throughout a duplex. In embodiments, a 3' terminus of the SS may contain one or more mismatches. In embodiments, two mismatches may be incorporated at a 3' terminus of a sense strand.In embodiments, an RNAi agent may include a SS and a AS complementary to at least a portion of a targetgene mRNA, wherein the AS comprises 2'-F modifications at AS positions 2 and 14 and the SS comprises 2'-F modifications at two or more positions of the SS that correspond to positions 7, 8, 9 or 19 of a 19- nucleotide SS.It will be appreciated by the ordinarily skilled artisan in the relevant art that the antisense strand may vary in length. In embodiments, an antisense strand of an RNAi agent may have a length of 21, 22, 23, 24, or 25 nucleotides.It will also be appreciated by the skilled artisan in the relevant art that the sense strand may vary in length. In embodiments, a sense strand of an RNAi agent may have a length of 19, 20, 21, 22, 23, 24, or 25 nucleotides.Exemplified modification patterns of RNAi agents of the disclosure are primarily depicted upon 19 / 21mer RNAi agents, i.e., an RNAi agent where the sense strand is 19 nucleotides in length, the antisense strand is 21 nucleotides in length, the 3'-end of the sense strand and the 5'-end of the antisense strand form a blunt end, and the 3'-end of the antisense strand of the RNAi agent forms a 2-nucleotide overhang with the 5'-end of the sense strand. The duplex region of a 19 / 21 mer RNAi agent therefore has a 19 nucleotide long complementary region between the sense strand and the antisense strand (though 100% complementarity of sense strand and antisense strand nucleotides is not necessarily required in the complementary region of an RNAi agent, as in certain embodiments, mismatch(es) may be present in the complementary region). In certain embodiments where an antisense strand of an RNAi agent of the disclosure is extended, such extension of the antisense strand of the RNAi agent is correspondingly made to the sense strand of the RNAi agent of the disclosure, thereby maintaining the blunt end / 2-nucleotide overhang end structure of the extended RNAi agent resulting from such extension. Accordingly, In embodiments, an antisense strand of an RNAi agent of the disclosure that has been extended by one nucleotide in length (relative to an original 21 DB1 / 167456146.4 38Attorney Docket No.: CTY-003PC / 139872-5003nucleotide long antisense strand of an original 19 / 21 mer RNAi agent) may have an extended length of 22 nucleotides while a corresponding sense strand of the RNAi agent has an extended length of 20 nucleotides, thereby forming a 20 / 22mer RNAi agent. Likewise, In embodiments, an antisense strand of an RNAi agent of the disclosure that has been extended by two nucleotides in length (relative to an original 21 nucleotide long antisense strand of an original 19 / 21 mer RNAi agent) may have an extended length of 23 nucleotides while a corresponding sense strand of the RNAi agent has an extended length of 21 nucleotides, thereby forming a 21 / 23mer RNAi agent. In embodiments, an antisense strand of an RNAi agent of the disclosure that has been extended by three nucleotides in length (relative to an original 21 nucleotide long antisense strand of an original 19 / 21 mer RNAi agent) may have an extended length of 24 nucleotides while a corresponding sense strand of the RNAi agent has an extended length of 22 nucleotides, thereby forming a 22 / 24mer RNAi agent. And In embodiments, an antisense strand of an RNAi agent of the disclosure that has been extended by four nucleotides in length (relative to an original 21 nucleotide long antisense strand of an original 19 / 21 mer RNAi agent) may have an extended length of 25 nucleotides while a corresponding sense strand of the RNAi agent has an extended length of 23 nucleotides, thereby forming a 23 / 25mer RNAi agent. For purpose of positional numbering of the modification patterns of the instant disclosure, in embodiments, addition of nucleotides to the antisense strand of an exemplified 19 / 21 mer RNAi agent (an RNAi agent having a sense strand of 19 nucleotides in length and an antisense strand of 21 nucleotides in length), or subtraction of nucleotides from the antisense strand of an exemplified 19 / 21 mer RNAi agent is performed at the 3'-end of the antisense strand, usually while performing offsetting additions to or subtractions from the corresponding 5'-end of the sense strand (thereby maintaining a blunt end / 2-nucleotide overhang end RNAi agent format, as noted above). Because additions to or subtractions from an exemplified 21 -nucleotide antisense strand are performed at the 3'-end of the antisense strand, in such embodiments, modification pattern positional numbering of the antisense strand remains fixed (e.g., for a 21 nucleotide long antisense strand that is extended by two nucleotides at the 3'-end of the antisense strand to a 23 nucleotide long antisense strand in a corresponding new 21 / 23mer RNAi agent format, positions 1-21 of the new 23 nucleotide antisense strand directly correspond to positions 1-21 of the original 19 / 21mer RNAi agent 21 nucleotide long antisense strand (as both antisense strands number from a shared position 1 at the 5'-end of the antisense strand), with new positions 22 and 23 added in the new 23 nucleotide long antisense strand of the new 21 / 23mer RNAi agent, effectively added to the 3'-end of the original 21 nucleotide long antisense strand of the original 19 / 21 mer RNAi agent. By way of further nonlimiting example, an antisense strand having a length of 21 nucleotides may be shortened to 20 or 19 nucleotides by removal of one or more 3'-terminalDB1 / 167456146.4 39Attorney Docket No.: CTY-003PC / 139872-5003nucleotides. For example, an original 19 / 21mer RNAi agent 21 -nucleotide antisense strand may be represented as 5'-N1 -N2*-N3-N4-N5-N6-N7-N8-N9-N10-N11 -N 12-N 13-N 14*-N 15-N16-N17-N18-N19-N20- N21-3', where N2* and N14* denote nucleotides including a chemical modification, with nucleotide positions numbered from the 5' terminus. Such an original antisense strand may be shortened to 20 nucleotides by subtracting the nucleotide at the 3'-terminus of the original 21 -nucleotide antisense strand, resulting in a 20 nucleotide long antisense strand in a new 18 / 20mer RNAi agent having, e.g., 5'-N1-N2*-N3-N4-N5-N6-N7- N8-N9-N10-N11-N12-N13-N14*-N15-N16-N17-N18-N19-N20-3' as the new 20 nucleotide long antisense strand sequence.Unless otherwise indicated, nucleotide positions of an antisense strand are numbered from the 5' terminus, with the 5'-terminal nucleotide designated as position 1, regardless of a total length of an antisense strand. Accordingly, chemical modifications recited at specific antisense-strand positions may refer to the indicated nucleotide position as counted from the 5' terminus and may remain fixed across antisense strands of different lengths.In embodiments, an antisense strand may include a region that is complementary to a corresponding region of a sense strand and may further include one or more non-complementary overhang nucleotides positioned at the 3'-terminus of the antisense strand. In such embodiments, a complementary region may define a duplex architecture of an RNAi agent.Unless otherwise indicated, nucleotide positions of a sense strand may be defined relative to a duplex architecture and a region of complementarity to an antisense strand. In embodiments, when length of a sense strand is varied by addition or removal of nucleotides within a complementary region, positional numbering of sense strand nucleotides shifts accordingly.In embodiments, variation in sense strand length may include addition or removal of one or more nucleotides within a complementary region of a sense strand that base-pairs with a corresponding region of an antisense strand. For example, a sense strand having a length of 19 nucleotides and a complementary region of 19 nucleotides may be lengthened to 21 nucleotides by addition of two nucleotides within a complementary region, such that the complementary region increases to 21 nucleotides and positional numbering of sensestrand nucleotides shifts accordingly. In such embodiments, a nucleotide designated as position 7 in a 19- nucleotide sense strand would be designated as position 9 in a 21 -nucleotide sense strand.By way of further non-limiting example, a sense strand having a length of 19 nucleotides and a complementary region of 19 nucleotides may be represented as 5'-S1-S2-S3-S4-S5-S6-S7*-S8-S9-S10- DB1 / 167456146.4 40Attorney Docket No.: CTY-003PC / 139872-5003S11-S12-S13-S14-S15-S16-S17-S18-S19-3'. In embodiments, a sense strand may be lengthened to 21 nucleotides by addition of two nucleotides at the 5'-terminus of the sense strand, e.g., 5'-S1 '-S2'-S3'-S4'-S5'- S6'-S7'-S8’-S9’*-S 10’-S 11 '-S12’-S 13'-S 14'-S15'-S16'-S17'-S 18'-S19'-S20'-S21 '-3', where position SN of the original RNAi agent is equivalent to position S(N+2)’ of the new RNAi agent sense strand and positioning of the modification at sense strand nucleotide 7 (S7*) of the original 19 / 21 mer RNAi agent in the specific nonlimiting example is therefore shifted to position 9 of the new, 5'-extended sense strand (S9’*) of the new 21 / 23mer RNAi agent, thereby maintaining the relationship of the original sense strand modification pattern to the corresponding original antisense strand modification pattern of the original 19 / 21 mer RNAi agent within the new, extended 21 / 23mer RNAi agent.In embodiments, chemical modifications at specific sense-strand positions are located within a complementary region and may be defined relative to an antisense strand and a duplex architecture. Accordingly, the positional designation of such modifications on an antisense strand may remain constant when antisense-strand length variation includes addition or removal of overhang nucleotides, yet modification pattern numbering will tend to shift upon the sense strand, when nucleotides are added to or removed from the 5'-end of the sense strand, extending or contracting the complementary region of the RNAi agent in the process of performing such additions to or subtractions from the 5'-end of the sense strand.In certain alternative embodiments, it is also contemplated that the 3'-end of a sense strand may be extended, thereby forming an overhang of the 3'-end of the sense strand relative to the 5'-end of the antisense strand. In such alternative embodiments, positional numbering of the sense strand of altered length (a sense strand having more than 19 nucleotides in length) will continue to be in reference to the sense strand nucleotide that pairs with the 5'-terminal nucleotide of the antisense strand being position 19 of the sense strand. Thus, in such alternative embodiments, extension of sense strand length will maintain positional numbering of modifications upon the sense strand (absent inclusion of other sense strand length changes at the 5'-end of the sense strand / 3'-end of the antisense strand, which will adjust sense strand positional numbering as described above).Unless otherwise specified, positional comparisons to “a 19-nucleotide sense strand” are to be made to a 19- nucleotide sense strand of a 19 / 21 mer RNAi agent as exemplified herein, in which the 3'-end (position 19) of the 19-nucleotide sense strand forms a blunt end with the 5'-end (position 1) of the 21 -nucleotide antisense strand.DB1 / 167456146.4 41Attorney Docket No.: CTY-003PC / 139872-5003Unless indicated otherwise, chemical modification patterns of a sense strand and / or an antisense strand as disclosed herein are exemplified without limitation with reference to an RNAi agent including a 19-nucleotide sense strand and a 21 -nucleotide antisense strand. In embodiments, positions of chemical modifications are described relative to respective sense and antisense strand lengths of a 19 / 21-mer RNAi agent having a blunt end formed by the 3'-end of the sense strand and the 5'-end of the antisense strand and also having a two-nucleotide overhang of the 3'-end of the antisense strand relative to the 5'-end of the sense strand. It will be appreciated by the ordinarily skilled artisan in the relevant art that, where modification patterns are exemplified herein with reference to a 19-nucleotide sense strand and a 21 -nucleotide antisense strand, positional designations of nucleotide modifications may be adjusted as disclosed herein when length of a sense strand and / or an antisense strand is varied, in accordance with the numbering conventions described herein.Transferrin receptor 2 (TFR2)The Transferrin receptor 2 (TFR2) protein, which is also known as hemochromatosis type 3 (HFE3), is a receptor protein belonging to the transferrin receptor-like family that is produced primarily in the liver. TFR2 is believed to be a putative “iron sensor” that fine-tunes iron homeostasis, inter alia, by regulating the levels of hepcidin, a master regulator of iron homeostasis. The TFR2 gene is located on chromosome 7, at the 7q22.1 region and has an open reading frame that spans approximately 21 kb and includes 18 exons. This gene encodes a single-pass type II membrane protein. This protein mediates cellular uptake of transferrin- bound iron, and is involved in iron homeostasis, hepatocyte function and erythrocyte differentiation. In humans, two isoforms of TFR2 is produced: TFR2 isoform alpha, the transcript of which includes all 18 exons, and TFR2 isoform beta, the transcript of which lacks exons 1 through 3 but includes a 142 base-insertion with respect to the alpha transcript at the 5’ end of exon 4. TFR2o is a protein of about 89 kDa encompassing 801 amino acids. The amino acid sequence of TFR2 isoform alpha, which is publicly available as GenBank Accession No. NP_003218.2, is provided below:MERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELRGPEPLGSRPRQ PNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGSCQACGDSVLVVSEDVNYEPDLDFHQGRLYWSD LQAMFLQFLGEGRLEDTIRQTSLRERVAGSAGMAALTQDIRAALSRQKLDHVWTDTHYVGLQFPDPAHPN TLHWVDEAGKVGEQLPLEDPDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVIS FAQKVTNAQDFGAQGVLIYPEPADFSQDPPKPSLSSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASS GLPSIPAQPISADIASRLLRKLKGPVAPQEWQGSLLGSPYHLGPGPRLRLVVNNHRTSTPINNIFGCIEGRSEDB1 / 167456146.4 42Attorney Docket No.: CTY-003PC / 139872-5003PDHYWIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSNGFRPRRSLLFISWDGGDFGSVGSTEWLEG YLSVLHLKAWYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEQWFTNPSWDAEVIRP LPMDSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSH DRLLPLDFGRYGDWLRHIGNLNEFSGDLKARGLTLQWVYSARGDYIRAAEKLRQEIYSSEERDERLTRMY NVRIMRVEFYFLSQYVSPADSPFRHIFMGRGDHTLGALLDHLRLLRSNSSGTPGATSSTGFQESRFRRQLA LLTWTLQGAANALSGDVWNIDNNF (SEQ ID NO: 1694).The amino acid sequence of TFR2 isoform beta, which lacks a transmembrane domain, which is publicly available as GenBank Accession No. NP_001193784.1, is provided below:MAALTQDIRAALSRQKLDHVWTDTHYVGLQFPDPAHPNTLHWVDEAGKVGEQLPLEDPDVYCPYSAIGNV TGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYPEPADFSQDPPKP SLSSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPISADIASRLLRKLKGPVAPQEWQG SLLGSPYHLGPGPRLRLWNNHRTSTPINNIFGCIEGRSEPDHYWIGAQRDAWGPGAAKSAVGTAILLELV RTFSSMVSNGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHLKAWYVSLDNAVLGDDKFHAKTSPL LTSLIESVLKQVDSPNHSGQTLYEQVVFTNPSWDAEVIRPLPMDSSAYSFTAFVGVPAVEFSFMEDDQAYP FLHTKEDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLDFGRYGDWLRHIGNLNEFSGDLKAR GLTLQWVYSARGDYIRAAEKLRQEIYSSEERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRGD HTLGALLDHLRLLRSNSSGTPGATSSTGFQESRFRRQLALLTWTLQGAANALSGDVWNIDNNF (SEQ ID NO: 1695).Iron is an essential element, which has roles in vital processes such as the electron transport chain, the distribution of oxygen throughout the body via hemoglobin, and as a cofactor in numerous enzymatic reactions. However, excess iron can be very toxic to the cell, e.g., because of its role in the formation of free radicals, which can oxidize proteins, lipids, and damage DNA and RNA. Human body needs 10-30 mg of iron per day, depending on age, sex, and life stage. The body acquires the vast majority of the iron from recycling of dead red blood cells by macrophages. The remainder is met by the dietary absorption of iron.Iron transport into the bloodstream is accomplished through transferrin, which transports iron through the blood to tissues throughout the body. On the surface of hepatocytes, Transferrin receptor 2 (TFR2) binds to transferrin and thereby allows iron entry in hepatic cells. In addition, transferrin receptor 2 also interacts with the BMP receptor complex, which is central to modulating expression of hepcidin, and thus responsible for regulating iron homeostasis.DB1 / 167456146.4 43Attorney Docket No.: CTY-003PC / 139872-5003However, in addition to its role as a master regulator of iron homeostasis, hepcidin plays a role in immunity. Michels etal., Hepcidin and Host Defense against Infectious Diseases, PLoS Pathog. (8):e1004998 (2015). Macrophages, monocytes and neutrophils secrete hepcidin in response to inflammation through the TLR-4 signaling pathway, the IL-6 stimulatory pathway, and / orthe bone morphogenetic protein-6 signaling pathway, among others. Peyssonnaux et al., TLR4-dependent hepcidin expression by myeloid cells in response to bacterial pathogens, Blood 107: 3727-3732 (2006); Theurl et al., Autocrine formation of hepcidin induces iron retention in human monocytes. Blood 111: 2392-2399 (2008); Sow et al., Role of STAT1, NF-KB, and C / EBPp in the macrophage transcriptional regulation of hepcidin by mycobacterial infection and IFN-y. Journal of Leukocyte Biology 86: 1247-1258 (2009); Wu et al., Hepcidin Regulation by BMP Signaling in Macrophages is Lipopolysaccharide Dependent, PLoS ONE 7(9): e44622 (2012); and Layoun and Santos Bacterial cell wall constituents induce hepcidin expression in macrophages through MyD88 signaling, Inflammation 35(4): 1500-1506 (2012). During times of iron overload, hepcidin expression is increased to reduce iron export from hepatocytes via ferroportin. Ferroportin is the only iron exporter in the body, and is expressed on the surface of enterocytes, macrophages and hepatocytes. Hepcidin tags ferroportin for internalization / degradation which prevents absorption of iron from the gut, and inhibits the release of iron from iron-recycling macrophages, leading to a reduction in Fe3+in the blood. Conversely, during times of iron deficiency, hepcidin expression is downregulated, leading to ferroportin stabilization on the cell surface, increased absorption of iron from the gut, the release of iron from stores in liver and iron-recycling macrophages, which leads to an increase in Fe3+in blood circulation. TFR2 is believed to play a role in iron homeostasis based on its ability to bind and be stabilized by iron-bound transferrin. For example, TFR2 that is not bound apo-transferrin (without iron) is believed to be subjected to lysosomal degradation. On the other hand, TFR2 bound to iron-loaded transferrin (holo-Transferrin) is believed to have increased half-life and is capable of stimulating hepcidin production. Thus, TFR2 is believed to be the putative “iron sensor” that finetunes this system, based on its ability to bind and be stabilized by iron-bound transferrin.In addition, while the overexpression of hepcidin during inflammation can restrict the availability of iron for pathogens during acute infection, in chronic or acute inflammatory conditions, this mimics iron overload independent of actual iron overload in a chronic disease setting, and thus leads to iron deficiency for hematopoiesis even as iron is stored in the liver and to the development of anemia of chronic disease. TFR2 plays a role in the pathology of anemia of chronic disease by further stimulating hepcidin production and thereby decreasing in Fe3+in the blood circulation. Anemia of inflammation is the second most common typeDB1 / 167456146.4 44Attorney Docket No.: CTY-003PC / 139872-5003of anemia, after iron-deficiency anemia, amounting to about 40% of all anemias. See, e.g., Weiss et al., Anemia of inflammation, Blood 133(1): 40-50 (2018).In addition, TFR2 plays roles in the pathology of other diseases such as -thalassemia, iron refractory iron deficiency anemia (I RIDA). 0-thalassemia, due to a deficiency in beta-globin production, the excessive free a-globin chains that are produced tend to aggregate or degrade, releasing toxic heme, porphyrins and iron, which produce reactive oxygen species (ROS). It has been shown that reduction of TFR2 leads to a reduced abundance of toxic free a-globin chains. IRIDA is a rare genetic condition that follows an autosomal recessive inheritance due to a defect in the TMPRSS6 gene encoding Matriptase-2, which exhibits iron deficiency anemia that is unresponsive to oral iron treatment. IRIDA patients have elevated levels of hepcidin. TFR2 is believed to be involved in hepcidin production in IRIDA.TRF2 also contributes to cancer-associated anemia via hepcidin overexpression. Anemia is very common in cancer patients, with 30 to 90% cancer patients suffering from anemia. Knight et al., Prevalence and Outcomes of Anemia in Cancer: a Systematic Review of the Literature, Am J Med. 116(suppl 7A):11 S— 26S (2004). Interestingly, high hepcidin levels are found in cancer patients and implicated in the pathogenesis anemia in cancer patients. See, e.g., Arvedson et al., Evaluation of serum hepcidin concentrations in cancer and leukemia patients, J Clin Oncol. 26(15S):20581 (2008); Sharma et al., Involvement of hepcidin in the anemia of multiple myeloma. Clin Cancer Res. 14(11 ):3262— 7 (2008); Fan et al., Hepcidin upregulation in lung cancer: A potential therapeutic target associated with immune infiltration, Front Immunol 12: 612144 (2021); Dong eta / ., Hepcidin is Upregulated and is a Potential Therapeutic Target Associated with Immunity in Glioma, Front Oncol. 12:963096 (2022). TFR2 is believed to be also involved in hepcidin production in cancer-associated anemia. Cancers with anemia of inflammation component include (solid cancer (without limitation, e.g., lung cancer, ovarian cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, kidney cancer, gynecological cancers (e.g., uterine cancer, endometrial cancer, ovarian cancer, cervical cancer, vaginal cancer, and vulvar cancer), head and neck cancer, esophageal cancer, stomach cancer, gastric cancer, pancreatic cancer, liver cancer (without limitation, e.g., hepatocellular carcinoma), and thyroid cancer), and blood cancers (without limitation, e.g., acute leukemia, chronic leukemia, Hodgkin’s lymphoma, Non-Hodgkin, lymphoma, multiple myeloma, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms, myeloma (e.g., monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, and extramedullary plasmacytoma), and myelofibrosis).DB1 / 167456146.4 45Attorney Docket No.: CTY-003PC / 139872-5003Accordingly, Transferrin receptor 2 (TFR2) is important to the pathology of hematological disease and disorders such as anemia (e.g., anemia of inflammation, cancer-associated anemia, and iron refractory iron deficiency anemia (IRIDA)), and p-thalassemia, making it a molecular target for treating, delaying progression of or preventing these diseases. See, Roetto et al., The Functional Versatility of Transferrin Receptor 2 and Its Therapeutic Value, Pharmaceuticals (Basel), 11 (4):115 (2018). In addition, TFR2 is a molecular target for treating, delaying progression of or preventing autoimmune diseases (e.g., rheumatoid arthritis and lupus), inflammatory bowel disease (e.g., Crohn’s Disease and ulcerative colitis), chronic kidney disease (CKD), and cancers with anemia of inflammation component, which include solid cancers (without limitation, e.g., lung cancer, ovarian cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, kidney cancer, gynecological cancers (e.g., uterine cancer, endometrial cancer, ovarian cancer, cervical cancer, vaginal cancer, and vulvar cancer), head and neck cancer, esophageal cancer, stomach cancer, gastric cancer, pancreatic cancer, liver cancer (without limitation, e.g., hepatocellular carcinoma), and thyroid cancer), and blood cancers (without limitation, e.g., acute leukemia, chronic leukemia, Hodgkin’s lymphoma, Non-Hodgkin, lymphoma, multiple myeloma, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms, myeloma (e.g., monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, and extramedullary plasmacytoma), and myelofibrosis.TFR2 Target SequencesIn embodiments, RNAi agents capable of inhibiting TFR2 expression are provided herein, and can be used to achieve a therapeutic benefit. Through examination of the TFR2 mRNA, including mRNAs of multiple different species (e.g., human, rhesus monkey, and mouse) and in vitro and in vivo testing, it has been discovered that certain sequences of TFR2 mRNA are useful as targeting sequences because they are more amenable than others to RNAi agent-mediated knockdown.Accordingly, in embodiments, RNAi agents provided herein are designed so as to have regions of complementarity to TFR2 mRNA (e.g., within a target sequence of TFR2 mRNA) for purposes of targeting the mRNA in cells and inhibiting its expression. The region of complementary is generally of a suitable length and base content to enable annealing of the RNAi agent (or a strand thereof) to TFR2 mRNA for purposes of inhibiting its expression. In embodiments, the region of complementarity is at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19 or at least 20 nucleotides in length. In embodiments, the RNAi agent provided herein has a region of complementarity to TFR2 that is in the range of 12 to 30 (e.g., 12 to 30, 12 to 22, 15 to 25, 17 to 21, 18 to 27, 19 to 27, or 15 to 30) nucleotides in length.DB1 / 167456146.4 46Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the RNAi agent provided herein has a region of complementarity to TFR2 that is 12, 13, 14, 15. 16. 17. 18. 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides in length.In embodiments, the RNAi agent disclosed herein comprises a region of complementarity (e.g., on an antisense strand of a double-stranded RNAi agent) that is at least partially complementary to TFR2. In embodiments, the RNAi agent disclosed herein comprises a region of complementarity (e.g., on an antisense strand of a double-stranded RNAi agent) that is fully complementary to TFR2. In embodiments, the region of complementarity of an RNAi agent (e.g., on an antisense strand of a double-stranded RNAi agent) is complementary to a contiguous sequence of nucleotides of TFR2 that is in the range of 12 to 20 nucleotides (e.g., 12 to 20, 12 to 18, 12 to 16, 12 to 14, 14 to 20, 14 to 18, 14 to 16, 16 to 20, 16 to 18, or 18 to 20) in length. In embodiments, the region of complementarity of an RNAi agent (e.g., on an antisense strand of a double-stranded RNAi agent) is complementary to a contiguous sequence of nucleotides of TFR2 that is 10, 11. 12. 13. 14. 15. 16. 17. 18. 19, or 20 contiguous nucleotides in length.In embodiments, the region of complementarity of an RNAi agent that is complementary to contiguous nucleotides of TFR2 spans the entire length of an antisense strand. In embodiments, the region of complementarity of an RNAi agent that is complementary to contiguous nucleotides of TFR2 spans a portion of the entire length of an antisense strand.In embodiments, the region of complementarity to TFR2 may have one or more mismatches compared with a corresponding sequence of TFR2 mRNA. A region of complementarity on an RNAi agent may have up to 1, up to 2, up to 3, up to 4, up to 5, etc. mismatches provided that it maintains the ability to form complementary base pairs with TFR2 mRNA under appropriate hybridization conditions. Alternatively, a region of complementarity on an RNAi agent may have no more than 1, no more than 2, no more than 3, no more than 4, or no more than 5 mismatches provided that it maintains the ability to form complementary base pairs with TFR2 mRNA under appropriate hybridization conditions. In embodiments, if there are more than one mismatches in a region of complementarity, they may be positioned consecutively (e.g., 2, 3, 4, or more in a row), or interspersed throughout the region of complementarity provided that the RNAi agent maintains the ability to form complementary base pairs with TFR2 mRNA under appropriate hybridization conditions. Exemplary target sequences in TFR2 for the RNAi agents disclosed herein include SEQ ID NOs: 677-1014. tyRNAIn aspects, the present disclosure provides a synthetic nucleic acid composition comprising an antisense strand, wherein the antisense strand comprises at least about 12 nucleotides and fewer than about 25DB1 / 167456146.4 47Attorney Docket No.: CTY-003PC / 139872-5003nucleotides, and wherein the antisense strand comprises a binding site for a PAZ domain of an RNA-induced silencing complex (RISC). In embodiments, the RISC comprises an Argonaute (AGO) protein selected from AG02 and AGO3. In embodiments, the AGO protein is AGO2. In embodiments, the AGO protein is AGO3. In embodiments, antisense strand has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides.In aspects, the present disclosure provides a method of making a pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier, and an antisense strand capable of inducing an assembly of a RISC, the method comprising (i) providing a tyRNA that is complementary to contiguous 12 to 19 nucleotides of a target RNA, wherein the tyRNA has been determined to be capable of binding PAZ domain of an RNA-induced silencing complex (RISC), and (ii) formulating the tyRNA for administration to a human patient. In embodiments, tyRNA has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides.In aspects, the present disclosure provides a method of making a pharmaceutical composition comprising an RNAi agent capable of interfering with a function of a target RNA, the method comprising (i) contacting an array of RNA molecules with an isolated AGO protein selected from AG03; (ii) isolating the RNA molecules that bind to the AGO protein and form a RNA molecule-AGO protein complex; and (iii) formulating one or more selected molecules for administration to a human patient. In embodiments, the RNA molecules have a length that is in the range of about 10 nucleotides to about 25 nucleotides, or about 12 nucleotides to about 20 nucleotides, or about 14 nucleotides to about 18 nucleotides. In embodiments, RNA molecules have a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides, or more. In embodiments, the AG03 protein is a mammalian AGO3 protein, a primate AG03 protein, or human AGO3 protein.In embodiments, the AG03 protein is immobilized on a solid support (e.g., a bead or a column). In embodiments, the method further comprises washing the RNA molecule-AGO3 protein complex. In embodiments, selecting comprises eluting the RNA molecules from the RNA molecule-AGO3 protein complex. In embodiments, the method further comprises sequencing the selected RNA molecules and repeating steps (i) and (ii).In aspects, the present disclosure provides a method of making a pharmaceutical composition comprising an RNAi agent capable of interfering with a function of a target RNA, the method comprising (i) contacting an array of RNA molecules with an isolated AGO protein selected from AGO2; (ii) isolating the RNA moleculesDB1 / 167456146.4 48Attorney Docket No.: CTY-003PC / 139872-5003that bind to the AGO protein and form a RNA molecule-AGO protein complex; and (iii) formulating one or more selected molecules for administration to a human patient. In embodiments, the RNA molecules have a length that is in the range of about 10 nucleotides to about 25 nucleotides, or about 12 nucleotides to about 20 nucleotides, or about 14 nucleotides to about 18 nucleotides. In embodiments, RNA molecules have a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides, or more. In embodiments, the AG02 protein is a mammalian AGO2 protein, a primate AG02 protein, or human AGO2 protein.In embodiments, the AG02 protein is immobilized on a solid support (e.g., a bead or a column). In embodiments, the method further comprises washing the RNA molecule-AGO2 protein complex. In embodiments, selecting comprises eluting the RNA molecules from the RNA molecule-AGO2 protein complex. In embodiments, the method further comprises sequencing the selected RNA molecules and repeating steps (i) and (ii).In aspects, the present disclosure provides a method of making a pharmaceutical composition comprising an RNAi agent capable of interfering with a function of a target RNA, the method comprising (i) contacting an array of RNA molecules with an isolated AGO protein to form a RNA molecule-AGO protein complex; (ii) contacting the complex with an exonuclease enzyme to generate fragments of the RNA molecules that are protected by the AGO protein; (iii) extracting the fragments; (iv) sequencing the fragments; (v) resynthesizing at least one of the fragments, optionally the synthesizing comprising incorporating at least one chemical modification; and (vi) formulating the at least one synthesized fragment for administration to a human patient. In embodiments, the AGO protein is AGO3 protein, optionally a mammalian AGO3 protein, a primate AGO3 protein, or human AGO3 protein. In embodiments, the AGO protein is AGO2 protein, optionally a mammalian AGO2 protein, a primate AGO2 protein, or human AG02 protein. In embodiments, the RNA molecules are complementary to the target RNA. In embodiments, the RNA molecules are chemically synthesized. In embodiments, the RNA molecules are prepared by in vitro translation. In embodiments, the RNA molecules are chemically modified according to any of the herein disclosed embodiments. In embodiments, at least one, or at least 5, or at least 10, or at least 20, or at least 40, or at least 60, more nucleotides at the 5’ and / or the 3’ end of the RNA molecules do not comprise backbone modifications (i.e., they comprise phosphodiester linkages). In embodiments, the exonuclease is selected from interferon-stimulated gene 20 kDa (ISG20), three prime repair exonuclease 1 (TREX1), and ERI1 (enhanced RNAi, also known as 3’hExo), poly(A)- specific ribonuclease (PARN), EXO5, or a variant thereof.DB1 / 167456146.4 49Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the AGO protein immobilized on a solid support (e.g., a bead or a column). In embodiments, the method further comprises washing the RNA molecule-AGO protein complex. In embodiments, the complex is contacted with an exonuclease enzyme before washing. In embodiments, the complex is contacted with an exonuclease enzyme in the presence of a manganese (Mn) ion (without limitation, e.g., Mn2+), a magnesium (Mg) ion (without limitation, e.g., Mg2+), or a combination thereof. In embodiments, the complex is contacted with an exonuclease enzyme after washing. In embodiments, extracting comprises eluting the RNA molecules from the RNA molecule-AGO protein complex.In embodiments, the synthesized fragment has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides, or about 20 nucleotides, or more.In aspects, the present disclosure provides a method of making a pharmaceutical composition comprising an RNAi agent capable of interfering with a function of a target RNA, the method comprising (i) contacting fragments of a target RNA molecules having lengths of about at least about 8 nucleotides with an isolated AGO3 protein to form a target RNA molecule-AGO protein complex; (ii) selecting the fragments that do not bind to the AGO protein; (iii) sequencing a fragment that does not bind to the AGO protein; (iv) preparing an RNAi agent that comprises an oligonucleotide that is antisense with respect to the target RNA and comprises a sequence that is complementary to a sequence that is immediately downstream (on 3’ side) with respect to the fragment; (vi) formulating the oligonucleotide for administration to a human patient. In embodiments, the oligonucleotide has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides. In embodiments, the oligonucleotide is chemically modified according to any of the herein disclosed embodiments.In aspects, the present disclosure provides a ribonucleic acid interference agent (RNAi agent) comprising an antisense strand that is complementary to a target nucleic acid. In embodiments, the target nucleic acid is TFR2 mRNA. In embodiments, the antisense strand has a length that is in the range of about 10 nucleotides to about 25 nucleotides, or about 12 nucleotides to about 19 nucleotides, or about 14 nucleotides to about 18 nucleotides. In embodiments, the antisense strand has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides, or about 20 nucleotides, or more. In embodiments, the antisense strand has a length that is less than about 22 nucleotides, or less than about 20 nucleotides, or less than about 18 nucleotides, or less than 17 nucleotides, or less than about 16 nucleotides, or less than about 15 nucleotides, or less than about 14DB1 / 167456146.4 50Attorney Docket No.: CTY-003PC / 139872-5003nucleotides, or less. In embodiments, the antisense strand has a length that is at least about 12 nucleotides, or at least about 13 nucleotides, or at least about 14 nucleotides, or at least about 16 nucleotides.In embodiments, the RNAi agent is a tiny RNA (tyRNA). In embodiments, tyRNA is shorter than 19 nucleotides is length. See Nakanishi, Are Argonaute-Associated Tiny RNAs Junk, Inferior miRNAs, or a New Type of Functional RNAs?, Front. Mol. Biosci. 8: 795356 (2021). In embodiments, the RNAi agent is an cleavage-inducing tyRNA (cityRNA). CityRNA are disclosed in WO2024206996, WO2024206999, WO2024206998, WO2024044759 and W02022006276, which are hereby incorporated by reference in their entirety. In embodiments, cityRNA has a length of about 12 nucleotides, or about 13 nucleotides, or about 14 nucleotides, or about 15 nucleotides, or about 16 nucleotides, or about 18 nucleotides. In embodiments, the RNAi agent is a short interfering RNA (siRNA). In embodiments, the siRNA has a length of about 20 to about 24 nucleotides. In embodiments, the RNAi agent is an microRNA (miRNA). In embodiments, miRNA is a small, single stranded, non-coding RNA molecules comprising between 19-25 nucleotides, that optionally comprise mismatches with the target.In embodiments, the RNAi agent is double-stranded, single-stranded or comprises a combination of single- and double-stranded segments. In embodiments, the RNAi agent is single stranded. In embodiments, where the guide stand is base-paired with a passenger strand (also referred to herein as a sense strand). In embodiments, where the guide stand comprises a nucleic acid sequence that is substantially complementary to a portion of the nucleotide sequence of a target RNA. In embodiments, where the passenger stand has a nucleic acid sequence that is substantially identical to the portion of the nucleotide sequence of a target RNA. In embodiments, the target RNA is an mRNA.In embodiments, the antisense strand is capable of binding an Argonaute (AGO) protein selected from AGO2, and AGO3 and form an antisense strand-AGO protein complex, which optionally comprises other proteins. In embodiments, the AGO protein is AGO2. In embodiments, the AGO protein is AGO3. In embodiments, the antisense strand is capable of binding one or more of the middle (MID) domain, the P-element-induced whimpy testes (PIWI) domain and the PIWI / Argonaute / Zwille (PAZ) domains of the AGO protein. In embodiments, the antisense strand is capable of binding the MID domain of the AGO protein. In embodiments, the antisense strand is capable of binding the PAZ domain so that the antisense strand AGO protein complex can undergo a transition to a mature a RNA-lnduced Silencing Complex (RISC). Accordingly, in embodiments, the complex is a mature RISC. In embodiments, the complex interacts with the target RNA. In embodiments, the complex interferes with a function of the target RNA. In embodiments, the complexDB1 / 167456146.4 51Attorney Docket No.: CTY-003PC / 139872-5003cleaves or slices the target RNA. In embodiments, the complex induces degradation of the target RNA. In embodiments, the complex induces repression of translation of the target RNA.RNAi AgentsDescribed herein are RNAi agents for reducing or suppressing expression of the TFR2 gene encoding for TFR2 (referred to herein as TFR2 RNAi agents). Each TFR2 RNAi agent comprises a sense strand and an antisense strand. In embodiments, the antisense strand of an RNAi agent may be referred to as a "guide strand." For example, if an antisense strand can engage with RNA-induced silencing complex (RISC) and bind to an Argonaut protein, or engage with or bind to one or more similar factors, and direct silencing of a target gene, it may be referred to as a guide strand. In embodiments a sense strand complementary with a guide strand may be referred to as a "passenger strand."For siRNA designs, the sense strand and antisense strand each can be 12 to 30 nucleotides in length. In embodiments, the sense and antisense strands each can be 14 to 26 nucleotides in length. The sense and antisense strands can be either the same length or they can be different lengths. In embodiments, the sense and antisense strands are each independently 14-21 nucleotides in length. In embodiments, the sense and antisense strands are each 12-26 nucleotides in length. In embodiments, the sense and antisense strands are each 19-23 nucleotides in length. In embodiments, the sense strand is about 19 nucleotides in length while the antisense strand is about 21 nucleotides in length. In embodiments, the sense strand is about 21 nucleotides in length while the antisense strand is about 23 nucleotides in length. In embodiments, the sense strand is 23 nucleotides in length and an antisense strand is 21 nucleotides in length. In embodiments, both the sense and antisense strands are each 21 nucleotides in length. In embodiments, the sense strand is 22 nucleotides in length and an antisense strand is 21 nucleotides in length. In embodiments, the sense strand is 19 nucleotides in length and an antisense strand is 21 nucleotides in length. In embodiments, the RNAi agent sense and antisense strands are each independently 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleotides in length. In embodiments, the double-stranded RNAi agent has a duplex length of about 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 nucleotides.In embodiments, the region of perfect or substantial complementarity between the sense strand and the antisense strand is 12-26 (e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26) nucleotides in length and occurs at or near the 5’ end of the antisense strand (e.g., this region may be separated from the 5’ end of the antisense strand by 0, 1, 2, 3, or 4 nucleotides that are not perfectly or substantially complementary).DB1 / 167456146.4 52Attorney Docket No.: CTY-003PC / 139872-5003The sense strand and antisense strand each contain a duplex region sequence that is 12 to 23 nucleobases in length, when sense and antisense strands anneal. An antisense strand duplex region sequence is 100% (perfectly) complementary or at least about 85% (substantially) complementary to a nucleotide sequence (sometimes referred to, e.g., as a target sequence) present in the TFR2 mRNA target. A duplex region sequence is 100% (perfectly) complementary or at least about 85% (substantially) complementary to a duplex region sequence in the antisense strand, and thus the sense strand duplex region sequence is perfectly identical or at least about 85% identical to a nucleotide sequence (target sequence) present in the TFR2 mRNA target. A sense strand duplex region sequence can be the same length as a corresponding antisense duplex region sequence or it can be a different length. In embodiments, the antisense strand duplex region sequence is 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotides in length. In embodiments, the sense strand duplex region sequence is 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotides in length.Examples of nucleotide sequences used in forming TFR2 RNAi agents are provided in Table 1, Table 2, Table 3, and Table 4.The TFR2 RNAi agent sense and antisense strands anneal to form a duplex. A sense strand and an antisense strand of an TFR2 RNAi agent may be partially, substantially, or fully complementary to each other. Within the complementary duplex region, the sense strand core stretch sequence is at least 85% complementary or 100% complementary to the antisense core stretch sequence. In embodiments, the sense strand core stretch sequence contains a sequence of at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, or at least 23 nucleotides that is at least 85% or 100% complementary to a corresponding 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 nucleotide sequence of the antisense strand core stretch sequence (i.e., the sense and antisense core stretch sequences of an TFR2 RNAi agent have a region of at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, or at least 23 nucleotides that is at least 85% base paired or 100% base paired).The sense strand and / or the antisense strand may optionally and independently contain an additional 1, 2, 3, 4, 5, or 6 nucleotides (overhang sequence) at the 3’ end, the 5’ end, or both the 3’ and 5’ ends of the duplex region sequences. The antisense strand additional nucleotides, if present, may or may not be complementary to the corresponding sequence in an TFR2 mRNA. The sense strand additional nucleotides, if present, may or may not be identical to the corresponding sequence in an TFR2 mRNA.DB1 / 167456146.4 53Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the RNAi agents of the disclosure, when contacted with a cell, are capable of reducing or suppressing expression of a Transferrin receptor 2 (TFR2) gene in the cell, compared to a pre-treatment control sample of the cell. In embodiments, the RNAi agents of the disclosure, when contacted with a cell, are capable of reducing or suppressing expression of a Transferrin receptor 2 (TFR2) gene in the cell, compared to a vehicle only treated control sample of the cell. Illustrative RNAi agents of the disclosure are listed in Table 1.DB1 / 167456146.4 54Attorney Docket No.: CTY-003PC / 139872-5003Table 1: Unmodified siRNA Duplex SequencesSEQ SEQ SEQAntisense Strand Sense Strand Seed SeedDuplex ID ID ID Target Sequence ID Sequence Sequence site SequenceNO: NO: NO:UACUGGAGGGAACUGG AACCCAGUUCCCUCC CAAACCCAGTTCCCTCDuplex3121UM 1 339 1325 ACUGGAG 677GUUUG AGUA CAGTT UAUGAGGUUUGGCUGC CCCAGGCAGCCAAAC GACCCAGGCAGCCAAADuplex3234UM 2 340 503 AUGAGGU 678CUGGGUC CUCAUA CCTCATT UAAGCCUGCAGGCUGU GGGACAGCCUGCAG GGGGGACAGCCTGCADuplex3298UM 3 341 271 AAGCCUG 679CCCCC GCUUA GGCTTC UGAAGCCUGCAGGCUG GGACAGCCUGCAGG GGGGACAGCCTGCAGDuplex3299UM 4 342 272 GAAGCCU 680UCCCC CUUCA GCTTCA UUGAAGCCUGCAGGCU GACAGCCUGCAGGC GGGACAGCCTGCAGGCDuplex3300UM 5 343 273 UGAAGCC 681GUCCC UUCAA TTCAG UCUGAAGCCUGCAGGC ACAGCCUGCAGGCU GGACAGCCTGCAGGCT Duplex3301UM 6 344 274 CUGAAGC 682UGUCC UCAGA TCAGG UCCUGAAGCCUGCAGG CAGCCUGCAGGCUU GACAGCCTGCAGGCTTDuplex3302UM 7 345 275 CCUGAAG 683CUGUC CAGGA CAGGA UCUCCUGAAGCCUGCAG GCCUGCAGGCUUCA CAGCCTGCAGGCTTCADuplex3304UM 8 346 277 CUCCUGA 684GCUG GGAGA GGAGGDB1 / 167456146.4 55Attorney Docket No.: CTY-003PC / 139872-5003UCCUCCUGAAGCCUGCA CCUGCAGGCUUCAG AGCCTGCAGGCTTCAGDuplex3305UM 9 347 278 CCUCCUG 685GGCU GAGGA GAGGG UAAAGCCGCUCCAUGCU CAAGCAUGGAGCGG CACAAGCATGGAGCGGDuplex3309UM 10 348 301 AAAGCCG 686UGUG CUUUA CTTTG UCAAAGCCGCUCCAUGC AAGCAUGGAGCGGC ACAAGCATGGAGCGGCDuplex3310UM 11 349 302 CAAAGCC 687UUGU UUUGA TTTGG UCCCAAAGCCGCUCCAU GCAUGGAGCGGCUU AAGCATGGAGCGGCTTDuplex3312UM 12 350 304 CCCAAAG 688GCUU UGGGA TGGGG UGUUGUUGCGCUCUCU UCCAGAGAGCGCAAC ATTCCAGAGAGCGCAADuplex3313UM 13 351 328 GUUGUUG 689GGAAU AACA CAACT UAGUUGUUGCGCUCUC CCAGAGAGCGCAACA TTCCAGAGAGCGCAACDuplex3314UM 14 352 329 AGUUGUU 690UGGAA ACUA AACTG UCAGUUGUUGCGCUCU CAGAGAGCGCAACAA TCCAGAGAGCGCAACADuplex3315UM 15 353 330 CAGUUGU 691CUGGA CUGA ACTGT UACAGUUGUUGCGCUC AGAGAGCGCAACAAC CCAGAGAGCGCAACAADuplex3316UM 16 354 331 ACAGUUG 692UCUGG UGUA CTGTC UGGACAGUUGUUGCGC AGAGCGCAACAACUG AGAGAGCGCAACAACTDuplex3318UM 17 355 333 GGACAGU 693UCUCU UCCA GTCCC UCGGUCUGAGAGGAUC CAAGAUCCUCUCAGA CCCAAGATCCTCTCAGDuplex3320UM 18 356 352 CGGUCUG 694UUGGG CCGA ACCGT UACGGUCUGAGAGGAU AAGAUCCUCUCAGAC CCAAGATCCTCTCAGADuplex3321UM 19 357 353 ACGGUCU 695CUUGG CGUA CCGTCDB1 / 167456146.4 56Attorney Docket No.: CTY-003PC / 139872-5003UGACGGUCUGAGAGGA AGAUCCUCUCAGACC CAAGATCCTCTCAGACDuplex3322UM 20 358 354 GACGGUC 696UCUUG GUCA CGTCT UAGACGGUCUGAGAGG GAUCCUCUCAGACCG AAGATCCTCTCAGACCDuplex3323UM 21 359 355 AGACGGU 697AUCUU UCUA GTCTA UUAGACGGUCUGAGAG AUCCUCUCAGACCGU AGATCCTCTCAGACCGDuplex3324UM 22 360 356 UAGACGG 698GAUCU CUAA TCTAC UGUAGACGGUCUGAGA UCCUCUCAGACCGUC GATCCTCTCAGACCGT Duplex3325UM 23 361 357 GUAGACG 699GGAUC UACA CTACC UUGGUAGACGGUCUGA CUCUCAGACCGUCUA TCCTCTCAGACCGTCTADuplex3327UM 24 362 359 UGGUAGA 700GAGGA CCAA CCAG UCUGGUAGACGGUCUG UCUCAGACCGUCUAC CCTCTCAGACCGTCTADuplex3328UM 25 363 360 CUGGUAG 701AGAGG CAGA CCAGC UGCUGGUAGACGGUCU CUCAGACCGUCUACC CTCTCAGACCGTCTACDuplex3329UM 26 364 361 GCUGGUA 702GAGAG AGCA CAGCG UCACGCUGGUAGACGG AGACCGUCUACCAGC TCAGACCGTCTACCAGDuplex3332UM 27 365 364 CACGCUG 703UCUGA GUGA CGTGT UCCACACGCUGGUAGAC CCGUCUACCAGCGU GACCGTCTACCAGCGTDuplex3335UM 28 366 367 CCACACG 704GGUC GUGGA GTGGA UUCCACACGCUGGUAGA CGUCUACCAGCGUG ACCGTCTACCAGCGTGDuplex3336UM 29 367 368 UCCACAC 705CGGU UGGAA TGGAA UUUCCACACGCUGGUAG GUCUACCAGCGUGU CCGTCTACCAGCGTGTDuplex3337UM 30 368 369 UUCCACA 706ACGG GGAAA GGAAGDB1 / 167456146.4 57Attorney Docket No.: CTY-003PC / 139872-5003UCCUUCCACACGCUGGU CUACCAGCGUGUGG GTCTACCAGCGTGTGGDuplex3339UM 31 369 371 CCUUCCA 707AGAC AAGGA AAGGC UUCCUCCUCCAGGUGC AGGGCACCUGGAGG AAAGGGCACCTGGAGGDuplex3346UM 32 370 398 UCCUCCU 708CCUUU AGGAA AGGAA UCUUCCUCCUCCAGGU GGCACCUGGAGGAG AGGGCACCTGGAGGAGDuplex3348UM 33 371 400 CUUCCUC 709GCCCU GAAGA GAAGA UUCUUCCUCCUCCAGGU GCACCUGGAGGAGG GGGCACCTGGAGGAGDuplex3349UM 34 372 401 UCUUCCU 710GCCC AAGAA GAAGAG UCCUCUUCCUCCUCCAG ACCUGGAGGAGGAA GCACCTGGAGGAGGAADuplex3351UM 35 373 403 ccucuuc 711GUGC GAGGA GAGGA UUCCUCUUCCUCCUCCA CCUGGAGGAGGAAG CACCTGGAGGAGGAAGDuplex3352UM 36 374 404 uccucuu 712GGUG AGGAA AGGAA UCUUCCUCUUCCUCCUC UGGAGGAGGAAGAG CCTGGAGGAGGAAGAGDuplex3354UM 37 375 406 CUUCCUC 713CAGG GAAGA GAAGA UUCUUCCUCUUCCUCCU GGAGGAGGAAGAGG CTGGAGGAGGAAGAGGDuplex3355UM 38 376 407 UCUUCCU 714CCAG AAGAA AAGAC UCGUCUUCCUCUUCCUC AGGAGGAAGAGGAA GGAGGAGGAAGAGGAADuplex3357UM 39 377 409 CGUCUUC 715 cucc GACGA GACGG UCCGUCUUCCUCUUCCU GGAGGAAGAGGAAG GAGGAGGAAGAGGAAGDuplex3358UM 40 378 410 CCGUCUU 716 ccuc ACGGA ACGGG UCCCGUCUUCCUCUUCC GAGGAAGAGGAAGAC AGGAGGAAGAGGAAGADuplex3359UM 41 379 411 CCCGUCU 717 uccu GGGA CGGGGDB1 / 167456146.4 58Attorney Docket No.: CTY-003PC / 139872-5003UGGAAUGAGGUUUGGC GCAGCCAAACCUCAU AGGCAGCCAAACCTCADuplex3360UM 42 380 506 GGAAUGA 718UGCCU UCCA TTCCC UGGGAAUGAGGUUUGG CAGCCAAACCUCAUU GGCAGCCAAACCTCATDuplex3361UM 43 381 507 GGGAAUG 719CUGCC CCCA TCCCT UAGGGAAUGAGGUUUG AGCCAAACCUCAUUC GCAGCCAAACCTCATTDuplex3362UM 44 382 508 AGGGAAU 720GCUGC CCUA CCCTG UCAGGGAAUGAGGUUU GCCAAACCUCAUUCC CAGCCAAACCTCATTCDuplex3363UM 45 383 509 CAGGGAA 721GGCUG CUGA CCTGG UCCCAGGGAAUGAGGU CAAACCUCAUUCCCU GCCAAACCTCATTCCCTDuplex3365UM 46 384 511 CCCAGGG 722UUGGC GGGA GGGC UGGAAGGCGACGUAGC UGGGCUACGUCGCC ACTGGGCTACGTCGCCDuplex3372UM 47 385 601 GGAAGGC 723CCAGU UUCCA TTCCG UCGGAAGGCGACGUAG GGGCUACGUCGCCU CTGGGCTACGTCGCCTDuplex3373UM 48 386 602 CGGAAGG 724CCCAG UCCGA TCCGA UCUCGGAAGGCGACGU GCUACGUCGCCUUC GGGCTACGTCGCCTTCDuplex3375UM 49 387 604 CUCGGAA 725AGCCC CGAGA CGAGG UCCUCGGAAGGCGACG CUACGUCGCCUUCC GGCTACGTCGCCTTCCDuplex3376UM 50 388 605 CCUCGGA 726UAGCC GAGGA GAGGG UGACCCUCGGAAGGCG CGUCGCCUUCCGAG TACGTCGCCTTCCGAGDuplex3379UM 51 389 608 GACCCUC 727ACGUA GGUCA GGTCC UCCUCACUGACCACCAA UGUUGGUGGUCAGU TGTGTTGGTGGTCAGT Duplex3387UM 52 390 649 CCUCACU 728CACA GAGGA GAGGADB1 / 167456146.4 59Attorney Docket No.: CTY-003PC / 139872-5003UCAGGUCAGGCUCAUAG AACUAUGAGCCUGAC TCAACTATGAGCCTGADuplex3391UM 53 391 672 CAGGUCA 729UUGA CUGA CCTGG UUCCAGGUCAGGCUCAU CUAUGAGCCUGACCU AACTATGAGCCTGACCDuplex3393UM 54 392 674 UCCAGGU 730AGUU GGAA TGGAT UAUCCAGGUCAGGCUCA UAUGAGCCUGACCU ACTATGAGCCTGACCTDuplex3394UM 55 393 675 AUCCAGG 731UAGU GGAUA GGATT UAAUCCAGGUCAGGCUC AUGAGCCUGACCUG CTATGAGCCTGACCTGDuplex3395UM 56 394 676 AAUCCAG 732AUAG GAUUA GATTT UAAAUCCAGGUCAGGCU UGAGCCUGACCUGG TATGAGCCTGACCTGG Duplex3396UM 57 395 677 AAAUCCA 733CAUA AUUUA ATTTC UGAAAUCCAGGUCAGGC GAGCCUGACCUGGA ATGAGCCTGACCTGGADuplex3397UM 58 396 678 GAAAUCC 734UCAU UUUCA TTTCC UGGAAAUCCAGGUCAGG AGCCUGACCUGGAU TGAGCCTGACCTGGATDuplex3398UM 59 397 679 GGAAAUC 735CUCA UUCCA TTCCA UGGCCUGGAGGUCGCU UGGAGCGACCUCCA ACTGGAGCGACCTCCADuplex3404UM 60 398 714 GGCCUGG 736CCAGU GGCCA GGCCA UAUGGCCUGGAGGUCG GAGCGACCUCCAGG TGGAGCGACCTCCAGGDuplex3406UM 61 399 716 AUGGCCU 737CUCCA CCAUA CCATG UCAUGGCCUGGAGGUC AGCGACCUCCAGGC GGAGCGACCTCCAGGCDuplex3407UM 62 400 717 CAUGGCC 738GCUCC CAUGA CATGT UAGGAACAUGGCCUGGA CCUCCAGGCCAUGU GACCTCCAGGCCATGTDuplex3412UM 63 401 722 AGGAACA 739GGUC UCCUA TCCTGDB1 / 167456146.4 60Attorney Docket No.: CTY-003PC / 139872-5003UCAGGAACAUGGCCUG CUCCAGGCCAUGUU ACCTCCAGGCCATGTT Duplex3413UM 64 402 723 CAGGAAC 740GAGGU CCUGA CCTGC UGCAGGAACAUGGCCU UCCAGGCCAUGUUC CCTCCAGGCCATGTTC Duplex3414UM 65 403 724 GCAGGAA 741GGAGG CUGCA CTGCA UUGCAGGAACAUGGCCU CCAGGCCAUGUUCC CTCCAGGCCATGTTCC Duplex3415UM 66 404 725 UGCAGGA 742GGAG UGCAA TGCAG UACUGCAGGAACAUGGC AGGCCAUGUUCCUG CCAGGCCATGTTCCTG Duplex3417UM 67 405 727 ACUGCAG 743CUGG CAGUA CAGTT UAACUGCAGGAACAUGG GGCCAUGUUCCUGC CAGGCCATGTTCCTGCDuplex3418UM 68 406 728 AACUGCA 744CCUG AGUUA AGTTC UGAACUGCAGGAACAUG GCCAUGUUCCUGCA AGGCCATGTTCCTGCA Duplex3419UM 69 407 729 GAACUGC 745GCCU GUUCA GTTCC UGGAACUGCAGGAACAU CCAUGUUCCUGCAG GGCCATGTTCCTGCAGDuplex3420UM 70 408 730 GGAACUG 746GGCC UUCCA TTCCT UAGGAACUGCAGGAACA CAUGUUCCUGCAGU GCCATGTTCCTGCAGT Duplex3421UM 71 409 731 AGGAACU 747UGGC UCCUA TCCTG UAUGGUGUCCUCCAGG GCGCCUGGAGGACA GGGCGCCTGGAGGACDuplex3427UM 72 410 758 AUGGUGU 748CGCCC CCAUA ACCATC UCUGAUGGUGUCCUCC CCUGGAGGACACCAU CGCCTGGAGGACACCADuplex3430UM 73 411 761 CUGAUGG 749AGGCG CAGA TCAGG UCCUGAUGGUGUCCUC CUGGAGGACACCAUC GCCTGGAGGACACCATDuplex3431UM 74 412 762 CCUGAUG 750CAGGC AGGA CAGGCDB1 / 167456146.4 61Attorney Docket No.: CTY-003PC / 139872-5003UGCCUGAUGGUGUCCU UGGAGGACACCAUCA CCTGGAGGACACCATCDuplex3432UM 75 413 763 GCCUGAU 751CCAGG GGCA AGGCA UUUUGCCUGAUGGUGU AGGACACCAUCAGGC GGAGGACACCATCAGGDuplex3435UM 76 414 766 UUUGCCU 752CCUCC AAAA CAAAC UAGGCUGGUUUGCCUG CAUCAGGCAAACCAG ACCATCAGGCAAACCA Duplex3442UM 77 415 773 AGGCUGG 753AUGGU CCUA GCCTT UAAGGCUGGUUUGCCU AUCAGGCAAACCAGC CCATCAGGCAAACCAGDuplex3443UM 78 416 774 AAGGCUG 754GAUGG CUUA CCTTC UCCCGAAGGCUGGUUU GGCAAACCAGCCUUC CAGGCAAACCAGCCTTDuplex3447UM 79 417 778 CCCGAAG 755GCCUG GGGA CGGGA UGUUCCCGAAGGCUGG AAACCAGCCUUCGGG GCAAACCAGCCTTCGGDuplex3450UM 80 418 781 GUUCCCG 756UUUGC AACA GAACG UACCCGUUCCCGAAGGC CAGCCUUCGGGAAC ACCAGCCTTCGGGAACDuplex3454UM 81 419 785 ACCCGUU 757UGGU GGGUA GGGTG UCACCCGUUCCCGAAGG AGCCUUCGGGAACG CCAGCCTTCGGGAACGDuplex3455UM 82 420 786 CACCCGU 758CUGG GGUGA GGTGG UAGCCUGCCACCCGUUC GGGAACGGGUGGCA TCGGGAACGGGTGGCADuplex3462UM 83 421 793 AGCCUGC 759CCGA GGCUA GGCTC UUCCCGGCCGAGCCUG UGGCAGGCUCGGCC GGTGGCAGGCTCGGCDuplex3471UM 84 422 802 UCCCGGC 760CCACC GGGAA CGGGAT UGAGCGGCCAUCCCGG CGGCCGGGAUGGCC CTCGGCCGGGATGGCCDuplex3480UM 85 423 811 GAGCGGC 761CCGAG GCUCA GCTCTDB1 / 167456146.4 62Attorney Docket No.: CTY-003PC / 139872-5003UUCAGAGCGGCCAUCCC CCGGGAUGGCCGCU GGCCGGGATGGCCGCDuplex3483UM 86 424 814 UCAGAGC 762GGCC CUGAA TCTGAC UGUCAGAGCGGCCAUC CGGGAUGGCCGCUC GCCGGGATGGCCGCTCDuplex3484UM 87 425 815 GUCAGAG 763CCGGC UGACA TGACT UGAGUCAGAGCGGCCA GGAUGGCCGCUCUG CGGGATGGCCGCTCTGDuplex3486UM 88 426 817 GAGUCAG 764UCCCG ACUCA ACTCA UCGUGGUCCAGCUUCU GCCAGAAGCUGGAC CCGCCAGAAGCTGGACDuplex3491UM 89 427 859 CGUGGUC 765GGCGG CACGA CACGT UCACACGUGGUCCAGCU GAAGCUGGACCACG CAGAAGCTGGACCACGDuplex3495UM 90 428 863 CACACGU 766UCUG UGUGA TGTGG UUCCACACGUGGUCCAG AGCUGGACCACGUG GAAGCTGGACCACGTGDuplex3497UM 91 429 865 UCCACAC 767CUUC UGGAA TGGAC UGUCCACACGUGGUCCA GCUGGACCACGUGU AAGCTGGACCACGTGTDuplex3498UM 92 430 866 GUCCACA 768GCUU GGACA GGACC UUCGGUCCACACGUGG GGACCACGUGUGGA CTGGACCACGTGTGGADuplex3501UM 93 431 869 UCGGUCC 769UCCAG CCGAA CCGAC UGUCGGUCCACACGUG GACCACGUGUGGAC TGGACCACGTGTGGACDuplex3502UM 94 432 870 GUCGGUC 770GUCCA CGACA CGACA UUGCGUGUCGGUCCAC CGUGUGGACCGACA CACGTGTGGACCGACADuplex3507UM 95 433 875 UGCGUGU 771ACGUG CGCAA CGCAC UGUGCGUGUCGGUCCA GUGUGGACCGACAC ACGTGTGGACCGACACDuplex3508UM 96 434 876 GUGCGUG 772CACGU GCACA GCACTDB1 / 167456146.4 63Attorney Docket No.: CTY-003PC / 139872-5003UAGUGCGUGUCGGUCC UGUGGACCGACACG CGTGTGGACCGACACGDuplex3509UM 97 435 877 AGUGCGU 773ACACG CACUA CACTA UACGUAGUGCGUGUCG GACCGACACGCACUA TGGACCGACACGCACTDuplex3513UM 98 436 881 ACGUAGU 774GUCCA CGUA ACGTG UAUCGACCCAGUGCAGG ACCCUGCACUGGGU ACACCCTGCACTGGGTDuplex3521UM 99 437 933 AUCGACC 775GUGU CGAUA CGATG UCCUCAUCGACCCAGUG UGCACUGGGUCGAU CCTGCACTGGGTCGATDuplex3525UM 100 438 937 CCUCAUC 776CAGG GAGGA GAGGC UGCUCUCCGACCUUCCC CCGGGAAGGUCGGA GGCCGGGAAGGTCGGDuplex3543UM 101 439 955 GCUCUCC 777GGCC GAGCA AGAGCA UUGCUCUCCGACCUUCC CGGGAAGGUCGGAG GCCGGGAAGGTCGGADuplex3544UM 102 440 956 UGCUCUC 778CGGC AGCAA GAGCAG UGCUGCUCUCCGACCU GGAAGGUCGGAGAG CGGGAAGGTCGGAGADuplex3546UM 103 441 958 GCUGCUC 779UCCCG CAGCA GCAGCT UAGCUGCUCUCCGACCU GAAGGUCGGAGAGC GGGAAGGTCGGAGAGDuplex3547UM 104 442 959 AGCUGCU 780UCCC AGCUA CAGCTG UCGGCAGCUGCUCUCC GUCGGAGAGCAGCU AGGTCGGAGAGCAGCTDuplex3551UM 105 443 963 CGGCAGC 781GACCU GCCGA GCCGC UGGCAGUAGACGUCAG ACCCUGACGUCUACU GGACCCTGACGTCTACDuplex3557UM 106 444 988 GGCAGUA 782GGUCC GCCA TGCCC UGGGCAGUAGACGUCA CCCUGACGUCUACU GACCCTGACGTCTACT Duplex3558UM 107 445 989 GGGCAGU 783GGGUC GCCCA GCCCCDB1 / 167456146.4 64Attorney Docket No.: CTY-003PC / 139872-5003UGCUCUCCCGUGACGU GCAACGUCACGGGA CGGCAACGTCACGGGADuplex3560UM 108 446 1021 GCUCUCC 784UGCCG GAGCA GAGCT UAGCUCUCCCGUGACG CAACGUCACGGGAGA GGCAACGTCACGGGAGDuplex3561UM 109 447 1022 AGCUCUC 785UUGCC GCUA AGCTG UCCAGCUCUCCCGUGAC ACGUCACGGGAGAG CAACGTCACGGGAGAGDuplex3563UM 110 448 1024 CCAGCUC 786GUUG CUGGA CTGGT UCACCAGCUCUCCCGUG GUCACGGGAGAGCU ACGTCACGGGAGAGCTDuplex3565UM 111 449 1026 CACCAGC 787ACGU GGUGA GGTGT UUACACCAGCUCUCCCG CACGGGAGAGCUGG GTCACGGGAGAGCTGGDuplex3567UM 112 450 1028 UACACCA 788UGAC UGUAA TGTAC UGUACACCAGCUCUCCC ACGGGAGAGCUGGU TCACGGGAGAGCTGGTDuplex3568UM 113 451 1029 GUACACC 789GUGA GUACA GTACG UCGUACACCAGCUCUCC CGGGAGAGCUGGUG CACGGGAGAGCTGGTGDuplex3569UM 114 452 1030 CGUACAC 790CGUG UACGA TACGC UCCUGCAGGUCUUCGG GGCCCGAAGACCUG GCGGCCCGAAGACCTGDuplex3596UM 115 453 1060 CCUGCAG 791GCCGC CAGGA CAGGA UUCCUGCAGGUCUUCG GCCCGAAGACCUGCA CGGCCCGAAGACCTGCDuplex3597UM 116 454 1061 UCCUGCA 792GGCCG GGAA AGGAC UUCUCCAGUUCCCAGGU GCACCUGGGAACUG GTGCACCTGGGAACTGDuplex3620UM 117 455 1274 UCUCCAG 793GCAC GAGAA GAGAC UGUCUCCAGUUCCCAG CACCUGGGAACUGG TGCACCTGGGAACTGGDuplex3621UM 118 456 1275 GUCUCCA 794GUGCA AGACA AGACCDB1 / 167456146.4 65Attorney Docket No.: CTY-003PC / 139872-5003UGGUCUCCAGUUCCCA ACCUGGGAACUGGA GCACCTGGGAACTGGADuplex3622UM 119 457 1276 GGUCUCC 795GGUGC GACCA GACCC UGGGUCUCCAGUUCCC CCUGGGAACUGGAG CACCTGGGAACTGGAGDuplex3623UM 120 458 1277 GGGUCUC 796AGGUG ACCCA ACCCC UGAAGGAAGGGAAGCCA CCUGGCUUCCCUUC CACCTGGCTTCCCTTCDuplex3624UM 121 459 1302 GAAGGAA 797GGUG CUUCA CTTCA UUGAAGGAAGGGAAGCC CUGGCUUCCCUUCC ACCTGGCTTCCCTTCCTDuplex3625UM 122 460 1303 UGAAGGA 798AGGU UUCAA TCAA UUUGAAGGAAGGGAAGC UGGCUUCCCUUCCU CCTGGCTTCCCTTCCTTDuplex3626UM 123 461 1304 UUGAAGG 799CAGG UCAAA CAAT UAUUGAAGGAAGGGAAG GGCUUCCCUUCCUU CTGGCTTCCCTTCCTTCDuplex3627UM 124 462 1305 AUUGAAG 800CCAG CAAUA AATC UGAUUGAAGGAAGGGAA GCUUCCCUUCCUUCA TGGCTTCCCTTCCTTCADuplex3628UM 125 463 1306 GAUUGAA 801GCCA AUCA ATCA UUGAUUGAAGGAAGGGA CUUCCCUUCCUUCAA GGCTTCCCTTCCTTCAADuplex3629UM 126 464 1307 UGAUUGA 802AGCC UCAA TCAA UUUGAUUGAAGGAAGG UUCCCUUCCUUCAAU GCTTCCCTTCCTTCAATDuplex3630UM 127 465 1308 UUGAUUG 803GAAGC CAAA CAAA UUUUGAUUGAAGGAAGG UCCCUUCCUUCAAUC CTTCCCTTCCTTCAATCDuplex3631UM 128 466 1309 UUUGAUU 804GAAG AAAA AAAC UGUUUGAUUGAAGGAAG CCCUUCCUUCAAUCA TTCCCTTCCTTCAATCADuplex3632UM 129 467 1310 GUUUGAU 805GGAA AACA AACCDB1 / 167456146.4 66Attorney Docket No.: CTY-003PC / 139872-5003UGGGUUUGAUUGAAGG CUUCCUUCAAUCAAA CCCTTCCTTCAATCAAADuplex3634UM 130 468 1312 GGGUUUG 806AAGGG CCCA CCCA UUGGGUUUGAUUGAAG UUCCUUCAAUCAAAC CCTTCCTTCAATCAAACDuplex3635UM 131 469 1313 UGGGUUU 807GAAGG CCAA CCAG UAACUGGGUUUGAUUGA CUUCAAUCAAACCCA TCCTTCAATCAAACCCADuplex3638UM 132 470 1316 AACUGGG 808AGGA GUUA GTTC UGAACUGGGUUUGAUU UUCAAUCAAACCCAG CCTTCAATCAAACCCAGDuplex3639UM 133 471 1317 GAACUGG 809GAAGG UUCA TTCC UGGGAACUGGGUUUGA CAAUCAAACCCAGUU TTCAATCAAACCCAGTTDuplex3641UM 134 472 1319 GGGAACU 810UUGAA CCCA CCCT UAGGGAACUGGGUUUG AAUCAAACCCAGUUC TCAATCAAACCCAGTTCDuplex3642UM 135 473 1320 AGGGAAC 811AUUGA CCUA CCTC UGAGGGAACUGGGUUU AUCAAACCCAGUUCC CAATCAAACCCAGTTCCDuplex3643UM 136 474 1321 GAGGGAA 812GAUUG CUCA CTCC UGGAGGGAACUGGGUU UCAAACCCAGUUCCC AATCAAACCCAGTTCCCDuplex3644UM 137 475 1322 GGAGGGA 813UGAUU UCCA TCCA UUGGAGGGAACUGGGU CAAACCCAGUUCCCU ATCAAACCCAGTTCCCTDuplex3645UM 138 476 1323 UGGAGGG 814UUGAU CCAA CCAG UCAACUGGAGGGAACUG CCCAGUUCCCUCCAG AACCCAGTTCCCTCCADuplex3647UM 139 477 1327 CAACUGG 815GGUU UUGA GTTGC UGCAACUGGAGGGAACU CCAGUUCCCUCCAGU ACCCAGTTCCCTCCAGDuplex3648UM 140 478 1328 GCAACUG 816GGGU UGCA TTGCADB1 / 167456146.4 67Attorney Docket No.: CTY-003PC / 139872-5003UUGCAACUGGAGGGAAC CAGUUCCCUCCAGUU CCCAGTTCCCTCCAGT Duplex3649UM 141 479 1329 UGCAACU 817UGGG GCAA TGCAT UAUGCAACUGGAGGGAA AGUUCCCUCCAGUU CCAGTTCCCTCCAGTTDuplex3650UM 142 480 1330 AUGCAAC 818CUGG GCAUA GCATC UGAUGCAACUGGAGGG GUUCCCUCCAGUUG CAGTTCCCTCCAGTTGDuplex3651UM 143 481 1331 GAUGCAA 819AACUG CAUCA CATCA UUGAUGCAACUGGAGG UUCCCUCCAGUUGCA AGTTCCCTCCAGTTGCDuplex3652UM 144 482 1332 UGAUGCA 820GAACU UCAA ATCAT UAUGAUGCAACUGGAGG UCCCUCCAGUUGCAU GTTCCCTCCAGTTGCATDuplex3653UM 145 483 1333 AUGAUGC 821GAAC CAUA CATC UUGGGAUGCUGGGAAG GGCCUUCCCAGCAU CAGGCCTTCCCAGCATDuplex3654UM 146 484 1353 UGGGAUG 822GCCUG CCCAA CCCAG UGCUGGGCUGGGAUGC CCAGCAUCCCAGCCC TCCCAGCATCCCAGCCDuplex3661UM 147 485 1360 GCUGGGC 823UGGGA AGCA CAGCC UCGGGAGGCAAUGUCU UGCAGACAUUGCCUC AGTGCAGACATTGCCT Duplex3667UM 148 486 1385 CGGGAGG 824GCACU CCGA CCCGC UAGGCGGGAGGCAAUG AGACAUUGCCUCCCG GCAGACATTGCCTCCCDuplex3670UM 149 487 1388 AGGCGGG 825UCUGC CCUA GCCTG UCAGGCGGGAGGCAAU GACAUUGCCUCCCG CAGACATTGCCTCCCGDuplex3671UM 150 488 1389 CAGGCGG 826GUCUG CCUGA CCTGC UUCCUCAGCAGGCGGG CCUCCCGCCUGCUG TGCCTCCCGCCTGCTGDuplex3678UM 151 489 1396 UCCUCAG 827AGGCA AGGAA AGGAADB1 / 167456146.4 68Attorney Docket No.: CTY-003PC / 139872-5003UGCUUCCUCAGCAGGC CCCGCCUGCUGAGG CTCCCGCCTGCTGAGGDuplex3681UM 152 490 1399 GCUUCCU 828GGGAG AAGCA AAGCT UAGCUUCCUCAGCAGGC CCGCCUGCUGAGGA TCCCGCCTGCTGAGGADuplex3682UM 153 491 1400 AGCUUCC 829GGGA AGCUA AGCTC UGAGCUUCCUCAGCAG CGCCUGCUGAGGAA CCCGCCTGCTGAGGAADuplex3683UM 154 492 1401 GAGCUUC 830GCGGG GCUCA GCTCA UUGAGCUUCCUCAGCAG GCCUGCUGAGGAAG CCGCCTGCTGAGGAAGDuplex3684UM 155 493 1402 UGAGCUU 831GCGG CUCAA CTCAA UUUGAGCUUCCUCAGCA CCUGCUGAGGAAGC CGCCTGCTGAGGAAGCDuplex3685UM 156 494 1403 UUGAGCU 832GGCG UCAAA TCAAA UUUUGAGCUUCCUCAGC CUGCUGAGGAAGCU GCCTGCTGAGGAAGCTDuplex3686UM 157 495 1404 UUUGAGC 833AGGC CAAAA CAAAG UCUUUGAGCUUCCUCAG UGCUGAGGAAGCUC CCTGCTGAGGAAGCTCDuplex3687UM 158 496 1405 CUUUGAG 834CAGG AAAGA AAAGG UGCCUUUGAGCUUCCU CUGAGGAAGCUCAAA TGCTGAGGAAGCTCAADuplex3689UM 159 497 1407 GCCUUUG 835CAGCA GGCA AGGCC UGGCCUUUGAGCUUCC UGAGGAAGCUCAAAG GCTGAGGAAGCTCAAADuplex3690UM 160 498 1408 GGCCUUU 836UCAGC GCCA GGCCC UUCUGAGCGGCCUUCG CAUCGAAGGCCGCU TGCATCGAAGGCCGCTDuplex3705UM 161 499 1553 UCUGAGC 837AUGCA CAGAA CAGAG UCUCUGAGCGGCCUUC AUCGAAGGCCGCUCA GCATCGAAGGCCGCTCDuplex3706UM 162 500 1554 CUCUGAG 838GAUGC GAGA AGAGCDB1 / 167456146.4 69Attorney Docket No.: CTY-003PC / 139872-5003UGGCUCUGAGCGGCCU CGAAGGCCGCUCAG ATCGAAGGCCGCTCAGDuplex3708UM 163 501 1556 GGCUCUG 839UCGAU AGCCA AGCCA UGAAGAGGAGACUUCUG CGCAGAAGUCUCCUC CCCGCAGAAGTCTCCTDuplex3710UM 164 502 1707 GAAGAGG 840CGGG UUCA CTTCA UUGAAGAGGAGACUUCU GCAGAAGUCUCCUCU CCGCAGAAGTCTCCTCDuplex3711UM 165 503 1708 UGAAGAG 841GCGG UCAA TTCAT UAUGAAGAGGAGACUUC CAGAAGUCUCCUCUU CGCAGAAGTCTCCTCT Duplex3712UM 166 504 1709 AUGAAGA 842UGCG CAUA TCATC UGAUGAAGAGGAGACUU AGAAGUCUCCUCUUC GCAGAAGTCTCCTCTTDuplex3713UM 167 505 1710 GAUGAAG 843CUGC AUCA CATCA UUGAUGAAGAGGAGACU GAAGUCUCCUCUUCA CAGAAGTCTCCTCTTCADuplex3714UM 168 506 1711 UGAUGAA 844UCUG UCAA TCAG UCUGAUGAAGAGGAGAC AAGUCUCCUCUUCAU AGAAGTCTCCTCTTCATDuplex3715UM 169 507 1712 CUGAUGA 845UUCU CAGA CAGC UGCUGAUGAAGAGGAGA AGUCUCCUCUUCAUC GAAGTCTCCTCTTCATCDuplex3716UM 170 508 1713 GCUGAUG 846CUUC AGCA AGCT UCCCAGCUGAUGAAGAG UCCUCUUCAUCAGCU TCTCCTCTTCATCAGCTDuplex3720UM 171 509 1717 CCCAGCU 847GAGA GGGA GGGA UGGCUUUGAGGUGCAG GUGCUGCACCUCAAA GCGTGCTGCACCTCAADuplex3726UM 172 510 1791 GGCUUUG 848CACGC GCCA AGCCG UCGGCUUUGAGGUGCA UGCUGCACCUCAAAG CGTGCTGCACCTCAAA Duplex3727UM 173 511 1792 CGGCUUU 849GCACG CCGA GCCGTDB1 / 167456146.4 70Attorney Docket No.: CTY-003PC / 139872-5003UACGGCUUUGAGGUGC GCUGCACCUCAAAGC GTGCTGCACCTCAAAGDuplex3728UM 174 512 1793 ACGGCUU 850AGCAC CGUA CCGTA UACUACGGCUUUGAGG GCACCUCAAAGCCGU CTGCACCTCAAAGCCGDuplex3731UM 175 513 1796 ACUACGG 851UGCAG AGUA TAGTG UACACUACGGCUUUGAG ACCUCAAAGCCGUAG GCACCTCAAAGCCGTADuplex3733UM 176 514 1798 ACACUAC 852GUGC UGUA GTGTA UUACACUACGGCUUUGA CCUCAAAGCCGUAGU CACCTCAAAGCCGTAG Duplex3734UM 177 515 1799 UACACUA 853GGUG GUAA TGTAC UGUACACUACGGCUUUG CUCAAAGCCGUAGUG ACCTCAAAGCCGTAGT Duplex3735UM 178 516 1800 GUACACU 854AGGU UACA GTACG UCGUACACUACGGCUUU UCAAAGCCGUAGUGU CCTCAAAGCCGTAGTG Duplex3736UM 179 517 1801 CGUACAC 855GAGG ACGA TACGT UCACGUACACUACGGCU AAAGCCGUAGUGUAC TCAAAGCCGTAGTGTADuplex3738UM 180 518 1803 CACGUAC 856UUGA GUGA CGTGA UUCACGUACACUACGGC AAGCCGUAGUGUAC CAAAGCCGTAGTGTAC Duplex3739UM 181 519 1804 UCACGUA 857UUUG GUGAA GTGAG UGCUCACGUACACUACG GCCGUAGUGUACGU AAGCCGTAGTGTACGTDuplex3741UM 182 520 1806 GCUCACG 858GCUU GAGCA GAGCC UGGCUCACGUACACUAC CCGUAGUGUACGUG AGCCGTAGTGTACGTGDuplex3742UM 183 521 1807 GGCUCAC 859GGCU AGCCA AGCCT UAGGCUCACGUACACUA CGUAGUGUACGUGA GCCGTAGTGTACGTGADuplex3743UM 184 522 1808 AGGCUCA 860CGGC GCCUA GCCTGDB1 / 167456146.4 71Attorney Docket No.: CTY-003PC / 139872-5003UCAGGCUCACGUACACU GUAGUGUACGUGAG CCGTAGTGTACGTGAGDuplex3744UM 185 523 1809 CAGGCUC 861ACGG CCUGA CCTGG UCCAGGCUCACGUACAC UAGUGUACGUGAGC CGTAGTGTACGTGAGCDuplex3745UM 186 524 1810 CCAGGCU 862UACG CUGGA CTGGA UUCCAGGCUCACGUACA AGUGUACGUGAGCC GTAGTGTACGTGAGCCDuplex3746UM 187 525 1811 UCCAGGC 863CUAC UGGAA TGGAC UUGUCCAGGCUCACGUA UGUACGUGAGCCUG AGTGTACGTGAGCCTGDuplex3748UM 188 526 1813 UGUCCAG 864CACU GACAA GACAA UUUGUCCAGGCUCACG GUACGUGAGCCUGG GTGTACGTGAGCCTGGDuplex3749UM 189 527 1814 UUGUCCA 865UACAC ACAAA ACAAC UGUUGUCCAGGCUCAC UACGUGAGCCUGGA TGTACGTGAGCCTGGADuplex3750UM 190 528 1815 GUUGUCC 866GUACA CAACA CAACG UCGUUGUCCAGGCUCA ACGUGAGCCUGGAC GTACGTGAGCCTGGACDuplex3751UM 191 529 1816 CGUUGUC 867CGUAC AACGA AACGC UUGCGUUGUCCAGGCU GUGAGCCUGGACAA ACGTGAGCCTGGACAADuplex3753UM 192 530 1818 UGCGUUG 868CACGU CGCAA CGCAG UCUGCGUUGUCCAGGC UGAGCCUGGACAAC CGTGAGCCTGGACAACDuplex3754UM 193 531 1819 CUGCGUU 869UCACG GCAGA GCAGT UACUGCGUUGUCCAGG GAGCCUGGACAACG GTGAGCCTGGACAACGDuplex3755UM 194 532 1820 ACUGCGU 870CUCAC CAGUA CAGTG UGCACUGCGUUGUCCA GCCUGGACAACGCA GAGCCTGGACAACGCADuplex3757UM 195 533 1822 GCACUGC 871GGCUC GUGCA GTGCTDB1 / 167456146.4 72Attorney Docket No.: CTY-003PC / 139872-5003UAGCACUGCGUUGUCCA CCUGGACAACGCAGU AGCCTGGACAACGCAGDuplex3758UM 196 534 1823 AGCACUG 872GGCU GCUA TGCTG UCAUGAAACUUGUCAUC GGGAUGACAAGUUU GGGGGATGACAAGTTTDuplex3762UM 197 535 1843 CAUGAAA 873CCCC CAUGA CATGC UGCAUGAAACUUGUCAU GGAUGACAAGUUUCA GGGGATGACAAGTTTCDuplex3763UM 198 536 1844 GCAUGAA 874CCCC UGCA ATGCC UGGCAUGAAACUUGUCA GAUGACAAGUUUCAU GGGATGACAAGTTTCADuplex3764UM 199 537 1845 GGCAUGA 875UCCC GCCA TGCCA UUGGCAUGAAACUUGUC AUGACAAGUUUCAUG GGATGACAAGTTTCATDuplex3765UM 200 538 1846 UGGCAUG 876AUCC CCAA GCCAA UUUGGCAUGAAACUUGU UGACAAGUUUCAUGC GATGACAAGTTTCATGCDuplex3766UM 201 539 1847 UUGGCAU 877CAUC CAAA CAAG UUCUUGGCAUGAAACUU ACAAGUUUCAUGCCA TGACAAGTTTCATGCCADuplex3768UM 202 540 1849 UCUUGGC 878GUCA AGAA AGAC UGUCUUGGCAUGAAACU CAAGUUUCAUGCCAA GACAAGTTTCATGCCAADuplex3769UM 203 541 1850 GUCUUGG 879UGUC GACA GACC UGGUCUUGGCAUGAAAC AAGUUUCAUGCCAAG ACAAGTTTCATGCCAAGDuplex3770UM 204 542 1851 GGUCUUG 880UUGU ACCA ACCA UCUGGUCUUGGCAUGA GUUUCAUGCCAAGAC AAGTTTCATGCCAAGACDuplex3772UM 205 543 1853 CUGGUCU 881AACUU CAGA CAGC UAAUGAGACUUGUCAGA CUUCUGACAAGUCUC CCCTTCTGACAAGTCTCDuplex3776UM 206 544 1875 AAUGAGA 882AGGG AUUA ATTGDB1 / 167456146.4 73Attorney Docket No.: CTY-003PC / 139872-5003UCAAUGAGACUUGUCAG UUCUGACAAGUCUCA CCTTCTGACAAGTCTCADuplex3777UM 207 545 1876 CAAUGAG 883AAGG UUGA TTGA UCUCAAUGAGACUUGUC CUGACAAGUCUCAUU TTCTGACAAGTCTCATTDuplex3779UM 208 546 1878 CUCAAUG 884AGAA GAGA GAGA UUCUCAAUGAGACUUGU UGACAAGUCUCAUUG TCTGACAAGTCTCATTGDuplex3780UM 209 547 1879 UCUCAAU 885CAGA AGAA AGAG UCACUCUCAAUGAGACU CAAGUCUCAUUGAGA GACAAGTCTCATTGAGDuplex3783UM 210 548 1882 CACUCUC 886UGUC GUGA AGTGT UACACUCUCAAUGAGAC AAGUCUCAUUGAGAG ACAAGTCTCATTGAGADuplex3784UM 211 549 1883 ACACUCU 887UUGU UGUA GTGTC UGACACUCUCAAUGAGA AGUCUCAUUGAGAGU CAAGTCTCATTGAGAGTDuplex3785UM 212 550 1884 GACACUC 888CUUG GUCA GTCC UGGACACUCUCAAUGAG GUCUCAUUGAGAGU AAGTCTCATTGAGAGTDuplex3786UM 213 551 1885 GGACACU 889ACUU GUCCA GTCCT UAGGACACUCUCAAUGA UCUCAUUGAGAGUG AGTCTCATTGAGAGTGTDuplex3787UM 214 552 1886 AGGACAC 890GACU UCCUA CCTG UUGGUUGGGAGAAUCC GGUGGAUUCUCCCA CAGGTGGATTCTCCCA Duplex3792UM 215 553 1910 UGGUUGG 891ACCUG ACCAA ACCAC UUGUGGUUGGGAGAAU UGGAUUCUCCCAACC GGTGGATTCTCCCAAC Duplex3794UM 216 554 1912 UGUGGUU 892CCACC ACAA CACAG UGUUCAUAGAGAGUCUG GGCAGACUCUCUAU TGGGCAGACTCTCTATDuplex3796UM 217 555 1933 GUUCAUA 893CCCA GAACA GAACADB1 / 167456146.4 74Attorney Docket No.: CTY-003PC / 139872-5003UUGUUCAUAGAGAGUCU GCAGACUCUCUAUGA GGGCAGACTCTCTATG Duplex3797UM 218 556 1934 UGUUCAU 894GCCC ACAA AACAG UCUGUUCAUAGAGAGUC CAGACUCUCUAUGAA GGCAGACTCTCTATGADuplex3798UM 219 557 1935 CUGUUCA 895UGCC CAGA ACAGG UACCUGUUCAUAGAGAG GACUCUCUAUGAACA CAGACTCTCTATGAACADuplex3800UM 220 558 1937 ACCUGUU 896UCUG GGUA GGTG UAACACCACCUGUUCAU CUAUGAACAGGUGG CTCTATGAACAGGTGGDuplex3806UM 221 559 1943 AACACCA 897AGAG UGUUA TGTTC UGAACACCACCUGUUCA UAUGAACAGGUGGU TCTATGAACAGGTGGTDuplex3807UM 222 560 1944 GAACACC 898UAGA GUUCA GTTCA UUGGUGAACACCACCUG AACAGGUGGUGUUC TGAACAGGTGGTGTTC Duplex3811UM 223 561 1948 UGGUGAA 899UUCA ACCAA ACCAA UCAAAGGCCGUGAAGGA AUUCCUUCACGGCCU CTATTCCTTCACGGCCTDuplex3839UM 224 562 2020 CAAAGGC 900AUAG UUGA TTGT UCUCCCACAAAGGCCGU UCACGGCCUUUGUG CTTCACGGCCTTTGTGDuplex3845UM 225 563 2026 CUCCCAC 901GAAG GGAGA GGAGT UGGACUCCCACAAAGGC CGGCCUUUGUGGGA CACGGCCTTTGTGGGADuplex3848UM 226 564 2029 GGACUCC 902CGUG GUCCA GTCCC UUGUCCUCCUUUGUGU UGCACACAAAGGAGG CCTGCACACAAAGGAGDuplex3863UM 227 565 2095 UGUCCUC 903GCAGG ACAA GACAC UAAGUGUCCUCCUUUGU ACACAAAGGAGGACA GCACACAAAGGAGGACDuplex3866UM 228 566 2098 AAGUGUC 904GUGC CUUA ACTTADB1 / 167456146.4 75Attorney Docket No.: CTY-003PC / 139872-5003UUAAGUGUCCUCCUUUG CACAAAGGAGGACAC CACACAAAGGAGGACADuplex3867UM 229 567 2099 UAAGUGU 905UGUG UUAA CTTAT UCAUAAGUGUCCUCCUU CAAAGGAGGACACUU CACAAAGGAGGACACTDuplex3869UM 230 568 2101 CAUAAGU 906UGUG AUGA TATGA UUCAUAAGUGUCCUCCU AAAGGAGGACACUUA ACAAAGGAGGACACTTDuplex3870UM 231 569 2102 UCAUAAG 907UUGU UGAA ATGAG UUCUCAUAAGUGUCCUC AGGAGGACACUUAUG AAAGGAGGACACTTATDuplex3872UM 232 570 2104 UCUCAUA 908CUUU AGAA GAGAA UGAGGAGCUGCCCUGC CUCGCAGGGCAGCU AGCTCGCAGGGCAGCTDuplex3895UM 233 571 2178 GAGGAGC 909GAGCU CCUCA CCTCA UCGGAUGAGGAGCUGC AGGGCAGCUCCUCA GCAGGGCAGCTCCTCADuplex3900UM 234 572 2183 CGGAUGA 910CCUGC UCCGA TCCGG UGGCGAUCGUGGCUGA GGCUCAGCCACGAU CCGGCTCAGCCACGATDuplex3917UM 235 573 2200 GGCGAUC 911GCCGG CGCCA CGCCT UAGGCGAUCGUGGCUG GCUCAGCCACGAUC CGGCTCAGCCACGATCDuplex3918UM 236 574 2201 AGGCGAU 912AGCCG GCCUA GCCTG UAGCAGGCGAUCGUGG CAGCCACGAUCGCCU CTCAGCCACGATCGCCDuplex3921UM 237 575 2204 AGCAGGC 913CUGAG GCUA TGCTG UCUCGUUGAGGUUCCC AUCGGGAACCUCAAC ACATCGGGAACCTCAA Duplex3936UM 238 576 2265 CUCGUUG 914GAUGU GAGA CGAGT UACUCGUUGAGGUUCC UCGGGAACCUCAACG CATCGGGAACCTCAACDuplex3937UM 239 577 2266 ACUCGUU 915CGAUG AGUA GAGTTDB1 / 167456146.4 76Attorney Docket No.: CTY-003PC / 139872-5003UGAGAACUCGUUGAGG GAACCUCAACGAGUU GGGAACCTCAACGAGTDuplex3941UM 240 578 2270 GAGAACU 916UUCCC CUCA TCTCT UGUAGAUCUCCUGCCG CUGCGGCAGGAGAU AGCTGCGGCAGGAGATDuplex3960UM 241 579 2367 GUAGAUC 917CAGCU CUACA CTACA UCUGUAGAUCUCCUGCC GCGGCAGGAGAUCU CTGCGGCAGGAGATCTDuplex3962UM 242 580 2369 CUGUAGA 918GCAG ACAGA ACAGC UAGCUGUAGAUCUCCUG GGCAGGAGAUCUACA GCGGCAGGAGATCTACDuplex3964UM 243 581 2371 AGCUGUA 919CCGC GCUA AGCTC UGAGCUGUAGAUCUCCU GCAGGAGAUCUACAG CGGCAGGAGATCTACADuplex3965UM 244 582 2372 GAGCUGU 920GCCG CUCA GCTCG UCGAGCUGUAGAUCUCC CAGGAGAUCUACAGC GGCAGGAGATCTACAGDuplex3966UM 245 583 2373 CGAGCUG 921UGCC UCGA CTCGG UCCGAGCUGUAGAUCUC AGGAGAUCUACAGCU GCAGGAGATCTACAGCDuplex3967UM 246 584 2374 CCGAGCU 922CUGC CGGA TCGGA UCUCUCUCCUCCGAGCU ACAGCUCGGAGGAG CTACAGCTCGGAGGAGDuplex3976UM 247 585 2383 CUCUCUC 923GUAG AGAGA AGAGA UCGCUCGUCUCUCUCC GGAGGAGAGAGACG TCGGAGGAGAGAGACGDuplex3983UM 248 586 2390 CGCUCGU 924UCCGA AGCGA AGCGA UGUCGCUCGUCUCUCU AGGAGAGAGACGAG GGAGGAGAGAGACGADuplex3985UM 249 587 2392 GUCGCUC 925CCUCC CGACA GCGACT UAGUCGCUCGUCUCUC GGAGAGAGACGAGC GAGGAGAGAGACGAGCDuplex3986UM 250 588 2393 AGUCGCU 926UCCUC GACUA GACTGDB1 / 167456146.4 77Attorney Docket No.: CTY-003PC / 139872-5003UCAGUCGCUCGUCUCU GAGAGAGACGAGCG AGGAGAGAGACGAGCGDuplex3987UM 251 589 2394 CAGUCGC 927CUCCU ACUGA ACTGA UUCAGUCGCUCGUCUC AGAGAGACGAGCGAC GGAGAGAGACGAGCGADuplex3988UM 252 590 2395 UCAGUCG 928UCUCC UGAA CTGAC UGUCAGUCGCUCGUCU GAGAGACGAGCGAC GAGAGAGACGAGCGACDuplex3989UM 253 591 2396 GUCAGUC 929CUCUC UGACA TGACA UUGUCAGUCGCUCGUC AGAGACGAGCGACU AGAGAGACGAGCGACTDuplex3990UM 254 592 2397 UGUCAGU 930UCUCU GACAA GACAC UGUGUCAGUCGCUCGU GAGACGAGCGACUG GAGAGACGAGCGACTGDuplex3991UM 255 593 2398 GUGUCAG 931CUCUC ACACA ACACG UCGUGUCAGUCGCUCG AGACGAGCGACUGAC AGAGACGAGCGACTGADuplex3992UM 256 594 2399 CGUGUCA 932UCUCU ACGA CACGC UUGCGUGUCAGUCGCU ACGAGCGACUGACAC AGACGAGCGACTGACADuplex3994UM 257 595 2401 UGCGUGU 933CGUCU GCAA CGCAT UUACAUGCGUGUCAGUC GCGACUGACACGCAU GAGCGACTGACACGCADuplex3998UM 258 596 2405 UACAUGC 934GCUC GUAA TGTAC UGUACAUGCGUGUCAG CGACUGACACGCAUG AGCGACTGACACGCATDuplex3999UM 259 597 2406 GUACAUG 935UCGCU UACA GTACA UUGUACAUGCGUGUCA GACUGACACGCAUGU GCGACTGACACGCATGDuplex4000UM 260 598 2407 UGUACAU 936GUCGC ACAA TACAA UUUGUACAUGCGUGUCA ACUGACACGCAUGUA CGACTGACACGCATGTDuplex4001UM 261 599 2408 UUGUACA 937GUCG CAAA ACAACDB1 / 167456146.4 78Attorney Docket No.: CTY-003PC / 139872-5003UGUUGUACAUGCGUGU CUGACACGCAUGUAC GACTGACACGCATGTA Duplex4002UM 262 600 2409 GUUGUAC 938CAGUC AACA CAACG UCACGUUGUACAUGCGU ACACGCAUGUACAAC TGACACGCATGTACAADuplex4005UM 263 601 2412 CACGUUG 939GUCA GUGA CGTGC UUUAUGCGCACGUUGUA UGUACAACGUGCGCA CATGTACAACGTGCGCDuplex4011UM 264 602 2419 UUAUGCG 940CAUG UAAA ATAAT UAUUAUGCGCACGUUGU GUACAACGUGCGCAU ATGTACAACGTGCGCA Duplex4012UM 265 603 2420 AUUAUGC 941ACAU AAUA TAATG UCAUUAUGCGCACGUUG UACAACGUGCGCAUA TGTACAACGTGCGCAT Duplex4013UM 266 604 2421 CAUUAUG 942UACA AUGA AATGC UGCAUUAUGCGCACGUU ACAACGUGCGCAUAA GTACAACGTGCGCATA Duplex4014UM 267 605 2422 GCAUUAU 943GUAC UGCA ATGCG UCGCAUUAUGCGCACGU CAACGUGCGCAUAAU TACAACGTGCGCATAATDuplex4015UM 268 606 2423 CGCAUUA 944UGUA GCGA GCGG UCCGCAUUAUGCGCACG AACGUGCGCAUAAUG ACAACGTGCGCATAATDuplex4016UM 269 607 2424 CCGCAUU 945UUGU CGGA GCGGG UCCCGCAUUAUGCGCAC ACGUGCGCAUAAUGC CAACGTGCGCATAATGDuplex4017UM 270 608 2425 CCCGCAU 946GUUG GGGA CGGGT UCCACCCGCAUUAUGCG UGCGCAUAAUGCGG CGTGCGCATAATGCGGDuplex4020UM 271 609 2428 CCACCCG 947CACG GUGGA GTGGA UACUCCACCCGCAUUAU GCAUAAUGCGGGUG GCGCATAATGCGGGTGDuplex4023UM 272 610 2431 ACUCCAC 948GCGC GAGUA GAGTTDB1 / 167456146.4 79Attorney Docket No.: CTY-003PC / 139872-5003UAACUCCACCCGCAUUA CAUAAUGCGGGUGG CGCATAATGCGGGTGGDuplex4024UM 273 611 2432 AACUCCA 949UGCG AGUUA AGTTC UGAACUCCACCCGCAUU AUAAUGCGGGUGGA GCATAATGCGGGTGGADuplex4025UM 274 612 2433 GAACUCC 950AUGC GUUCA GTTCT UAGAACUCCACCCGCAU UAAUGCGGGUGGAG CATAATGCGGGTGGAGDuplex4026UM 275 613 2434 AGAACUC 951UAUG UUCUA TTCTA UUAGAACUCCACCCGCA AAUGCGGGUGGAGU ATAATGCGGGTGGAGTDuplex4027UM 276 614 2435 UAGAACU 952UUAU UCUAA TCTAC UGUAGAACUCCACCCGC AUGCGGGUGGAGUU TAATGCGGGTGGAGTTDuplex4028UM 277 615 2436 GUAGAAC 953AUUA CUACA CTACT UAAGUAGAACUCCACCC GCGGGUGGAGUUCU ATGCGGGTGGAGTTCTDuplex4030UM 278 616 2438 AAGUAGA 954GCAU ACUUA ACTTC UGAAGUAGAACUCCACC CGGGUGGAGUUCUA TGCGGGTGGAGTTCTADuplex4031UM 279 617 2439 GAAGUAG 955CGCA CUUCA CTTCC UGGAAGUAGAACUCCAC GGGUGGAGUUCUAC GCGGGTGGAGTTCTACDuplex4032UM 280 618 2440 GGAAGUA 956CCGC UUCCA TTCCT UAGGAAGUAGAACUCCA GGUGGAGUUCUACU CGGGTGGAGTTCTACTDuplex4033UM 281 619 2441 AGGAAGU 957CCCG UCCUA TCCTT UAAGGAAGUAGAACUCC GUGGAGUUCUACUU GGGTGGAGTTCTACTT Duplex4034UM 282 620 2442 AAGGAAG 958ACCC CCUUA CCTTT UAAAGGAAGUAGAACUC UGGAGUUCUACUUC GGTGGAGTTCTACTTCDuplex4035UM 283 621 2443 AAAGGAA 959CACC CUUUA CTTTCDB1 / 167456146.4 80Attorney Docket No.: CTY-003PC / 139872-5003UGAAAGGAAGUAGAACU GGAGUUCUACUUCC GTGGAGTTCTACTTCCTDuplex4036UM 284 622 2444 GAAAGGA 960CCAC UUUCA TTCC UGGAAAGGAAGUAGAAC GAGUUCUACUUCCUU TGGAGTTCTACTTCCTTDuplex4037UM 285 623 2445 GGAAAGG 961UCCA UCCA TCCC UGGGAAAGGAAGUAGAA AGUUCUACUUCCUUU GGAGTTCTACTTCCTTTDuplex4038UM 286 624 2446 GGGAAAG 962CUCC CCCA CCCA UUGGGAAAGGAAGUAGA GUUCUACUUCCUUUC GAGTTCTACTTCCTTTCDuplex4039UM 287 625 2447 UGGGAAA 963ACUC CCAA CCAG UACUGGGAAAGGAAGUA UCUACUUCCUUUCCC GTTCTACTTCCTTTCCCDuplex4041UM 288 626 2449 ACUGGGA 964GAAC AGUA AGTA UUACUGGGAAAGGAAGU CUACUUCCUUUCCCA TTCTACTTCCTTTCCCADuplex4042UM 289 627 2450 UACUGGG 965AGAA GUAA GTAC UACGUACUGGGAAAGGA CUUCCUUUCCCAGUA TACTTCCTTTCCCAGTADuplex4045UM 290 628 2453 ACGUACU 966AGUA CGUA CGTG UCACGUACUGGGAAAGG UUCCUUUCCCAGUAC ACTTCCTTTCCCAGTACDuplex4046UM 291 629 2454 CACGUAC 967AAGU GUGA GTGT UACACGUACUGGGAAAG UCCUUUCCCAGUACG CTTCCTTTCCCAGTACGDuplex4047UM 292 630 2455 ACACGUA 968GAAG UGUA TGTC UGACACGUACUGGGAAA CCUUUCCCAGUACGU TTCCTTTCCCAGTACGTDuplex4048UM 293 631 2456 GACACGU 969GGAA GUCA GTCG UCGACACGUACUGGGAA CUUUCCCAGUACGU TCCTTTCCCAGTACGTGDuplex4049UM 294 632 2457 CGACACG 970AGGA GUCGA TCGCDB1 / 167456146.4 81Attorney Docket No.: CTY-003PC / 139872-5003UAUGAAGAUGUGGCGG GUUCCGCCACAUCUU CCGTTCCGCCACATCT Duplex4052UM 295 633 2489 AUGAAGA 971AACGG CAUA TCATG UCAUGAAGAUGUGGCG UUCCGCCACAUCUUC CGTTCCGCCACATCTTDuplex4053UM 296 634 2490 CAUGAAG 972GAACG AUGA CATGG UCCCAUGAAGAUGUGGC CCGCCACAUCUUCAU TTCCGCCACATCTTCATDuplex4055UM 297 635 2492 CCCAUGA 973GGAA GGGA GGGC UGCCCAUGAAGAUGUG CGCCACAUCUUCAUG TCCGCCACATCTTCATGDuplex4056UM 298 636 2493 GCCCAUG 974GCGGA GGCA GGCC UAGCAGCCGCAGGUGG GGACCACCUGCGGC CTGGACCACCTGCGGCDuplex4084UM 299 637 2540 AGCAGCC 975UCCAG UGCUA TGCTG UAGCAGGGCUAGCUGA GCGUCAGCUAGCCC CGGCGTCAGCTAGCCCDuplex4094UM 300 638 2624 AGCAGGG 976CGCCG UGCUA TGCTC UGUGAGCAGGGCUAGC UCAGCUAGCCCUGC CGTCAGCTAGCCCTGCDuplex4097UM 301 639 2627 GUGAGCA 977UGACG UCACA TCACC UCCCGCUAAGCGCAUUG GCCAAUGCGCUUAG CAGCCAATGCGCTTAG Duplex4119UM 302 640 2664 CCCGCUA 978GCUG CGGGA CGGGG UGUUAUCAAUGUUCCAG GUCUGGAACAUUGAU ATGTCTGGAACATTGATDuplex4120UM 303 641 2685 GUUAUCA 979ACAU AACA AACA UUGUUAUCAAUGUUCCA UCUGGAACAUUGAUA TGTCTGGAACATTGATADuplex4121UM 304 642 2686 UGUUAUC 980GACA ACAA ACAA UUUGUUAUCAAUGUUCC CUGGAACAUUGAUAA GTCTGGAACATTGATAADuplex4122UM 305 643 2687 UUGUUAU 981AGAC CAAA CAACDB1 / 167456146.4 82Attorney Docket No.: CTY-003PC / 139872-5003UAGUUGUUAUCAAUGUU GGAACAUUGAUAACA CTGGAACATTGATAACADuplex4124UM 306 644 2689 AGUUGUU 982CCAG ACUA ACTT UAAGUUGUUAUCAAUGU GAACAUUGAUAACAA TGGAACATTGATAACAADuplex4125UM 307 645 2690 AAGUUGU 983UCCA CUUA CTTC UGAAGUUGUUAUCAAUG AACAUUGAUAACAAC GGAACATTGATAACAACDuplex4126UM 308 646 2691 GAAGUUG 984UUCC UUCA TTCT UAGAAGUUGUUAUCAAU ACAUUGAUAACAACU GAACATTGATAACAACTDuplex4127UM 309 647 2692 AGAAGUU 985GUUC UCUA TCTG UCAGAAGUUGUUAUCAA CAUUGAUAACAACUU AACATTGATAACAACTTDuplex4128UM 310 648 2693 CAGAAGU 986UGUU CUGA CTGA UUCAGAAGUUGUUAUCA AUUGAUAACAACUUC ACATTGATAACAACTTCDuplex4129UM 311 649 2694 UCAGAAG 987AUGU UGAA TGAG UGAGGAGCAGAGGAGC AGAGCUCCUCUGCU CAAGAGCTCCTCTGCT Duplex4130UM 312 650 2748 GAGGAGC 988UCUUG CCUCA CCTCG UCGAGGAGCAGAGGAG GAGCUCCUCUGCUC AAGAGCTCCTCTGCTCDuplex4131UM 313 651 2749 CGAGGAG 989CUCUU CUCGA CTCGC UGCGAGGAGCAGAGGA AGCUCCUCUGCUCC AGAGCTCCTCTGCTCC Duplex4132UM 314 652 2750 GCGAGGA 990GCUCU UCGCA TCGCT UAGCGAGGAGCAGAGG GCUCCUCUGCUCCU GAGCTCCTCTGCTCCT Duplex4133UM 315 653 2751 AGCGAGG 991AGCUC CGCUA CGCTT UAGCAAUGAGAGGUGGA AGUCCACCUCUCAUU AGAGTCCACCTCTCATTDuplex4163UM 316 654 2800 AGCAAUG 992CUCU GCUA GCTGDB1 / 167456146.4 83Attorney Docket No.: CTY-003PC / 139872-5003UAUCAGCAAUGAGAGGU CCACCUCUCAUUGCU GTCCACCTCTCATTGCTDuplex4166UM 317 655 2803 AUCAGCA 993GGAC GAUA GATC UGAUCAGCAAUGAGAGG CACCUCUCAUUGCUG TCCACCTCTCATTGCTGDuplex4167UM 318 656 2804 GAUCAGC 994UGGA AUCA ATCA UGUGUGGAUAUCUGUG CAGCACAGAUAUCCA CCCAGCACAGATATCCDuplex4170UM 319 657 2866 GUGUGGA 995CUGGG CACA ACACA UUGUGUGGAUAUCUGU AGCACAGAUAUCCAC CCAGCACAGATATCCADuplex4171UM 320 658 2867 UGUGUGG 996GCUGG ACAA CACAC UCAGCUACACUGCAGGG AGCCCUGCAGUGUA CCAGCCCTGCAGTGTADuplex4176UM 321 659 2889 CAGCUAC 997CUGG GCUGA GCTGA UUCAGCUACACUGCAGG GCCCUGCAGUGUAG CAGCCCTGCAGTGTAGDuplex4177UM 322 660 2890 UCAGCUA 998GCUG CUGAA CTGAC UUUAACCGACAGUAUGA GGUCAUACUGUCGG ACGGTCATACTGTCGGDuplex4178UM 323 661 2920 UUAACCG 999CCGU UUAAA TTAAT UAUUAACCGACAGUAUG GUCAUACUGUCGGU CGGTCATACTGTCGGTDuplex4179UM 324 662 2921 AUUAACC 1000ACCG UAAUA TAATC UGAUUAACCGACAGUAU UCAUACUGUCGGUUA GGTCATACTGTCGGTTDuplex4180UM 325 663 2922 GAUUAAC 1001GACC AUCA AATCA UUGAUUAACCGACAGUA CAUACUGUCGGUUAA GTCATACTGTCGGTTAADuplex4181UM 326 664 2923 UGAUUAA 1002UGAC UCAA TCAG UCUGAUUAACCGACAGU AUACUGUCGGUUAAU TCATACTGTCGGTTAATDuplex4182UM 327 665 2924 CUGAUUA 1003AUGA CAGA CAGADB1 / 167456146.4 84Attorney Docket No.: CTY-003PC / 139872-5003UUCUGAUUAACCGACAG UACUGUCGGUUAAUC CATACTGTCGGTTAATCDuplex4183UM 328 666 2925 UCUGAUU 1004UAUG AGAA AGAG UCUCUGAUUAACCGACA ACUGUCGGUUAAUCA ATACTGTCGGTTAATCADuplex4184UM 329 667 2926 CUCUGAU 1005GUAU GAGA GAGA UUCUCUGAUUAACCGAC CUGUCGGUUAAUCA TACTGTCGGTTAATCAGDuplex4185UM 330 668 2927 UCUCUGA 1006AGUA GAGAA AGAG UACCACCUGUUGGCCAU UUAUGGCCAACAGGU CCTTATGGCCAACAGGDuplex4192UM 331 669 3076 ACCACCU 1007AAGG GGUA TGGTC UCACCACAGACCACCUG AACAGGUGGUCUGU CCAACAGGTGGTCTGTDuplex4200UM 332 670 3084 CACCACA 1008UUGG GGUGA GGTGA UUCACCACAGACCACCU ACAGGUGGUCUGUG CAACAGGTGGTCTGTGDuplex4201UM 333 671 3085 UCACCAC 1009GUUG GUGAA GTGAA UUUCACCACAGACCACC CAGGUGGUCUGUGG AACAGGTGGTCTGTGGDuplex4202UM 334 672 3086 UUCACCA 1010UGUU UGAAA TGAAA UUUUCACCACAGACCAC AGGUGGUCUGUGGU ACAGGTGGTCTGTGGTDuplex4203UM 335 673 3087 UUUCACC 1011CUGU GAAAA GAAAG UACGUGGUCCAGCUUC CCAGAAGCUGGACCA CGCCAGAAGCTGGACCDuplex3492UM 336 674 860 ACGUGGU 1012UGGCG CGUA ACGTG UUGUCGGUCCACACGU ACCACGUGUGGACC GGACCACGTGTGGACCDuplex3503UM 337 675 871 UGUCGGU 1013GGUCC GACAA GACAC UCUCCAGUUCCCAGGU UGCACCUGGGAACU TGTGCACCTGGGAACTDuplex3619UM 338 676 1273 CUCCAGU 1014GCACA GGAGA GGAGADB1 / 167456146.4 85Attorney Docket No.: CTY-003PC / 139872-5003As used herein, an overhang comprises 1, 2, 3, 4, 5, or 6 nucleotides at the 5’ and / or 3’ end of the sense strand duplex region sequence and / or antisense strand duplex region sequence. In embodiments, the TFR2 RNAi agent has an antisense strand having a 3’ extension. In embodiments, the TFR2 RNAi agent comprises an antisense strand having a 3’ extension of 1, 2, 3, 4, 5, or 6 nucleotides in length. In other embodiments, an TFR2 RNAi agent comprises an antisense strand having a 3’ extension of 1, 2, or 3 nucleotides in length. In embodiments, one or more of the antisense strand overhang nucleotides comprise uracil or thymidine nucleotides or nucleotides that are complementary to the corresponding TFR2 mRNA sequence. In embodiments, the 3’ antisense strand sequence region (optionally including an overhang) includes or consists of one of the following sequences, but is not limited to: AUA, UGCUU, CUG, UG, UGCC, CUGCC, CGU, CUU, UGCCUA, CUGCCU, UGCCU, UGAUU, GCCUAU, T, TT, U, UU (each listed 5’— 3’).In embodiments, the 3’ end of the antisense strand can include additional abasic residues (Ab). An "abasic residue" or "abasic site" is a nucleotide or nucleoside that lacks a nucleobase at the T position of the sugar. In embodiments, Ab or AbAb can be added to the 3’ end of the antisense strand. In embodiments, the abasic residue(s) can be added as inverted abasic residues (invAb). (See, e.g., F. Czauderna, Nucleic Acids Res, 2003, 31(11), 2705-16).In embodiments, the TFR2 RNAi agent may comprise a sense strand having a 3’ extension of 1, 2, 3, 4, or 5 nucleotides in length. In embodiments, one or more of the sense strand overhang nucleotides comprises adenosine, uracil, or thymidine nucleotides, AT dinucleotide, or nucleotides that correspond to nucleotides in the TFR2 mRNA sequence. In embodiments, the 3’-terminal region of the sense strand (optionally including an overhang) includes or consists of one of the following sequences, but is not limited to: T, UT, TT, UU, UUT, TTT, or TTTT (each listed 5’ to 3’).In embodiments, the 3’ end of the sense strand may include additional abasic residues. In embodiments, UUAb, UAb, or Ab are added to the 3’ end of the sense strand. In embodiments, the one or more abasic residues added to the 3’ end of the sense strand are inverted (invAb). In embodiments, one or more inverted abasic residues or abasic sites may be inserted between the targeting ligand and the nucleobase sequence of the sense strand of the RNAi agent. In embodiments, the inclusion of one or more inverted abasic residues or abasic sites at or near the terminal end or terminal ends of the sense strand of an RNAi agent allows for enhanced activity or other desired properties of an RNAi agent.In embodiments, the TFR2 RNAi agent may comprise a sense strand having a 5’ overhang of 1, 2, 3, 4, 5, or 6 nucleotides in length. In embodiments, one or more of the sense strand overhang nucleotides comprise DB1 / 167456146.4 86Attorney Docket No.: CTY-003PC / 139872-5003uracil or adenosine nucleotides or nucleotides that correspond to nucleotides in the TFR2 mRNA sequence. In embodiments, the sense strand 5 -terminal region (optionally including an overhang) includes one of the following sequences, but is not limited to: CA, AUAGGC, AUAGG, AUAG, AUA, A, AA, AC, GCA, GGCA, GGC, UAUCA, UAUC, UCA, UAU, U, UU (each listed 5’ to 3’). A sense strand can have a 3’ overhang and / or a 5’ overhang.In embodiments, the 5’ end of the sense strand can include one or more additional abasic residues (e.g., (Ab) or (AbAb)). In embodiments, the one or more abasic residues added to the 5’ end of the sense strand can be inverted (e.g., invAb). In embodiments, one or more inverted abasic residues can be inserted between the targeting ligand and the nucleobase sequence of the sense strand of the RNAi agent. In embodiments, the inclusion of one or more inverted abasic residues at or near the terminal end or terminal ends of the sense strand of an RNAi agent may allow for enhanced activity or other desired properties of an RNAi agent. In embodiments, the abasic (deoxyribose) residue can be replaced with a ribitol (abasic ribose) residue. Examples of sequences used in forming TFR2 RNAi agents are provided in Table 1, Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent antisense strand includes a sequence of any of the sequences in Table 1, Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent antisense strand includes the sequence of nucleotides (from 5’ end— >3’ end) 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, 2-12, 2-13, 2-14, 2-15, 2-16, 2-17, 2-18, 2-19, 2-20, 2-21, 2-22, 2-23, 3-14, 3- 15, 1-16, 3-17, 3-18, 3-19, 3-20, 3-21, 3-22, 3-23, 4-15, 4-16, 4-17, 4-18, 4-19, 4-20, 4-21, 4-22, 4-23, 5-16, 5-17, 5-18, 5-19, 5-20, 5-21, 5-22, 5-23, 6-18, 6-19, 6-20, 6-21, 6-22, 6-23, 7-17, 7-18, 7-19, 7-20, 7-21, 7- 22, 7-23, 8-20, 8-21, 8-22, 8-23, 9-21, 9-22, or 9-23 of any of the sequences in Table 1, Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent antisense strand comprises or consists of a sequence of any one of the modified sequences in Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent antisense strand includes the sequence of any of the sequences in Table 1, Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent sense strand includes the sequence of nucleotides (from 5’ end^3’ end) 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 2-12, 2-13, 2-14, 2-16, 2-17, 2-18, 2-19, 2-20, 2-21, 3-13, 3-14, 3-15, 3-16, 3-17, 3-18, 3-19, 3-20, 3-21, 4-14, 4-15, 4-16, 4-17, 4-18, 4-19, 4- 20, 4-21, 5-15, 5-16, 5-17, 5-18, 5-19, 5-20, 5-21, 6-16, 6-17, 6-18, 6-19, 6-20, 6-21, 7-17, 7-18, 7-19, 7-20, or 7-21, of any of the sequences in Table 1, Table 2, Table 3, and Table 4. In embodiments, the TFR2 RNAi agent sense strand comprises or consists of a modified sequence of any one of the modified sequences in Table 2, Table 3, and Table 4.DB1 / 167456146.4 87Attorney Docket No.: CTY-003PC / 139872-5003In embodiments, the antisense strand of an TFR2 RNAi agent disclosed herein differs by 0, 1, 2, or 3 nucleotides from any of the antisense strand sequences in Table 1, Table 2, Table 3, and Table 4. In embodiments, the sense strand of an TFR2 RNAi agent disclosed herein differs by 0, 1, 2, or 3 nucleotides from any of the sense strand sequences in Table 1, Table 2, Table 3, and Table 4.In embodiments an RNAi agent disclosed herein comprises an antisense strand comprising a sequence as set forth in any one of SEQ ID NOs: 1-338 or SEQ ID NOs: 1353-1690. In embodiments, the RNAi agent comprises an antisense strand comprising a contiguous sequence of nucleotides that is in the range of 12 to 20 nucleotides (e.g., 12 to 20, 12 to 18, 12 to 16, 12 to 14, 14 to 20, 14 to 18, 14 to 16, 16 to 20, 16 to 18, or 18 to 20 nucleotides) in length of any of the sequences as set forth in any one of SEQ ID NOs: 1-338 or SEQ ID NOs: 1353-1690. In embodiments, the RNAi agent comprises an antisense strand comprising a contiguous sequence of nucleotides of a sequence as set forth in any one of SEQ ID NOs: 1-338 or SEQ ID NOs: 1353- 1690 that is 12, 13, 14, 15, 16, 17, 18, 19, or 20 contiguous nucleotides in length. In embodiments, the RNAi agent comprises an antisense strand that consists of a sequence as set forth in any one of SEQ ID NOs: 1- 338 or SEQ ID NOs: 1353-1690. In embodiments, the RNAi agent comprises an antisense strand comprising a contiguous sequence of nucleotides of a sequence as set forth in any one of SEQ ID NOs: 1-338, which comprises at least one chemical modification, wherein the RNAi agent further comprises an unpaired vinyl phosphonate-modified U nucleotide (vinu), positioned at the 5’-terminus of the antisense strand. In embodiments, the RNAi agent comprises an antisense strand comprising a contiguous sequence of nucleotides of a sequence as set forth in any one of SEQ ID NOs: 1-338, which comprises at least one chemical modification present in SEQ ID NOs: 1353-1690, wherein the chemical modifications is or comprises an unpaired vinyl phosphonate-modified U nucleotide (vinu), positioned at the 5’-terminus of the antisense strand. In embodiments, the RNAi agent comprises an antisense strand comprising a contiguous sequence of nucleotides of a sequence as set forth in any one of SEQ ID NOs: 1-338, which comprises at least one chemical modification, wherein the RNAi agent further comprises a vinyl phosphonate-modified U nucleotide (vinu), positioned at the 5’-terminus of the antisense strand, optionally wherein the vinyl phosphonate-modified U nucleotide (vinu) is paired with an A nucleotide, which is optionally located at or near 3' -terminus of the sense strand.In embodiments, the RNAi agent disclosed herein comprises a sense strand sequence as set forth in in any one of SEQ ID NOs: 339-676 or their chemically modified versions as set forth in one of SEQ ID NOs: 1015- 1352. In embodiments, the RNAi agent has a sense strand that comprises at least 12 (e.g., at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, or at DB1 / 167456146.4 88Attorney Docket No.: CTY-003PC / 139872-5003least 23) contiguous nucleotides of a sequence as set forth in in any one of SEQ ID NOs: 339-676 or their chemically modified versions as set forth in one of SEQ ID NOs: 1015-1352. In embodiments, the RNAi agent has a sense strand that comprises a contiguous sequence of nucleotides that is in the range of 7 to 36 nucleotides (e.g., 12 to 30, 12 to 27, 12 to 22, 15 to 25, 17 to 21, 18 to 27, 19-27, 20-36, or 15 to 36 nucleotides) in length of any of the sequences as set forth in any one of SEQ ID NOs: 339-676 or their chemically modified versions as set forth in one of SEQ ID NOs: 1015-1352. In embodiments, the RNAi agent has a sense strand that comprises a contiguous sequence of nucleotides of a sequence as set forth in any one of SEQ ID NOs: 339-676 or SEQ ID NOs: 1015-1352 that is 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 nucleotides in length. In embodiments, the RNAi agent has a sense strand that consists of a sequence as set forth in any one of SEQ ID NOs: 339-676 or SEQ ID NOs: 1015-1352.In embodiments, the RNAi agent provided herein comprises a sense strand comprising a sequence as set forth in any one of SEQ ID NOs: 339-676 and an antisense strand comprising a complementary sequence selected from SEQ ID NOs: 1-338, as is also arranged in Table 1.In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1, and the sense strand comprises a sequence as set forth in SEQ ID NO: 339. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 2, and the sense strand comprises a sequence as set forth in SEQ ID NO: 340. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 3, and the sense strand comprises a sequence as set forth in SEQ ID NO: 341. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 4, and the sense strand comprises a sequence as set forth in SEQ ID NO: 342. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 5, and the sense strand comprises a sequence as set forth in SEQ ID NO: 343. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 6, and the sense strand comprises a sequence as set forth in SEQ ID NO: 344. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 7, and the sense strand comprises a sequence as set forth in SEQ ID NO: 345. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 8, and the sense strand comprises a sequence as set forth in SEQ ID NO: 346. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 9, and the sense strand comprises a sequence as set forth in SEQ ID NO: 347. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 10, and the sense strand comprises a sequence as set forth in SEQ ID NO: 348. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 11, and the sense strand comprises a sequence as DB1 / 167456146.4 89Attorney Docket No.: CTY-003PC / 139872-5003set forth in SEQ ID NO: 349. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 12, and the sense strand comprises a sequence as set forth in SEQ ID NO: 350. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 13, and the sense strand comprises a sequence as set forth in SEQ ID NO: 351. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 14, and the sense strand comprises a sequence as set forth in SEQ ID NO: 352. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 15, and the sense strand comprises a sequence as set forth in SEQ ID NO: 353. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 16, and the sense strand comprises a sequence as set forth in SEQ ID NO: 354. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 17, and the sense strand comprises a sequence as set forth in SEQ ID NO: 355. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 18, and the sense strand comprises a sequence as set forth in SEQ ID NO: 356. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 19, and the sense strand comprises a sequence as set forth in SEQ ID NO: 357. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 20, and the sense strand comprises a sequence as set forth in SEQ ID NO: 358. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 21, and the sense strand comprises a sequence as set forth in SEQ ID NO: 359. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 22, and the sense strand comprises a sequence as set forth in SEQ ID NO: 360. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 23, and the sense strand comprises a sequence as set forth in SEQ ID NO: 361. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 24, and the sense strand comprises a sequence as set forth in SEQ ID NO: 362. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 25, and the sense strand comprises a sequence as set forth in SEQ ID NO: 363. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 26, and the sense strand comprises a sequence as set forth in SEQ ID NO: 364. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 27, and the sense strand comprises a sequence as set forth in SEQ ID NO: 365. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 28, and the sense strand comprises a sequence as set forth in SEQ ID NO: 366. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 29, and the sense strand comprises a sequence as set forth in SEQ ID NO: 367. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 30, and the sense strand comprises a sequence as set forth in SEQ ID NO: 368. In embodiments, the antisense strandDB1 / 167456146.4 90Attorney Docket No.: CTY-003PC / 139872-5003comprises a sequence as set forth in SEQ ID NO: 31, and the sense strand comprises a sequence as set forth in SEQ ID NO: 369. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 32, and the sense strand comprises a sequence as set forth in SEQ ID NO: 370. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 33, and the sense strand comprises a sequence as set forth in SEQ ID NO: 371. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 34, and the sense strand comprises a sequence as set forth in SEQ ID NO: 372. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 35, and the sense strand comprises a sequence as set forth in SEQ ID NO: 373. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 36, and the sense strand comprises a sequence as set forth in SEQ ID NO: 374. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 37, and the sense strand comprises a sequence as set forth in SEQ ID NO: 375. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 38, and the sense strand comprises a sequence as set forth in SEQ ID NO: 376. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 39, and the sense strand comprises a sequence as set forth in SEQ ID NO: 377. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 40, and the sense strand comprises a sequence as set forth in SEQ ID NO: 378. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 41, and the sense strand comprises a sequence as set forth in SEQ ID NO: 379. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 42, and the sense strand comprises a sequence as set forth in SEQ ID NO: 380. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 43, and the sense strand comprises a sequence as set forth in SEQ ID NO: 381. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 44, and the sense strand comprises a sequence as set forth in SEQ ID NO: 382. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 45, and the sense strand comprises a sequence as set forth in SEQ ID NO: 383. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 46, and the sense strand comprises a sequence as set forth in SEQ ID NO: 384. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 47, and the sense strand comprises a sequence as set forth in SEQ ID NO: 385. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 48, and the sense strand comprises a sequence as set forth in SEQ ID NO: 386. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 49, and the sense strand comprises a sequence as set forth in SEQ ID NO: 387. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 50, and the senseDB1 / 167456146.4 91Attorney Docket No.: CTY-003PC / 139872-5003strand comprises a sequence as set forth in SEQ ID NO: 388. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 51, and the sense strand comprises a sequence as set forth in SEQ ID NO: 389. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 52, and the sense strand comprises a sequence as set forth in SEQ ID NO: 390. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 53, and the sense strand comprises a sequence as set forth in SEQ ID NO: 391. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 54, and the sense strand comprises a sequence as set forth in SEQ ID NO: 392. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 55, and the sense strand comprises a sequence as set forth in SEQ ID NO: 393. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 56, and the sense strand comprises a sequence as set forth in SEQ ID NO: 394. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 57, and the sense strand comprises a sequence as set forth in SEQ ID NO: 395. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 58, and the sense strand comprises a sequence as set forth in SEQ ID NO: 396. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 59, and the sense strand comprises a sequence as set forth in SEQ ID NO: 397. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 60, and the sense strand comprises a sequence as set forth in SEQ ID NO: 398. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 61, and the sense strand comprises a sequence as set forth in SEQ ID NO: 399. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 62, and the sense strand comprises a sequence as set forth in SEQ ID NO: 400. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 63, and the sense strand comprises a sequence as set forth in SEQ ID NO: 401. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 64, and the sense strand comprises a sequence as set forth in SEQ ID NO: 402. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 65, and the sense strand comprises a sequence as set forth in SEQ ID NO: 403. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 66, and the sense strand comprises a sequence as set forth in SEQ ID NO: 404. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 67, and the sense strand comprises a sequence as set forth in SEQ ID NO: 405. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 68, and the sense strand comprises a sequence as set forth in SEQ ID NO: 406. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 69, and the sense strand comprises a sequence as set forth in SEQ ID NO: 407. InDB1 / 167456146.4 92Attorney Docket No.: CTY-003PC / 139872-5003embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 70, and the sense strand comprises a sequence as set forth in SEQ ID NO: 408. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 71, and the sense strand comprises a sequence as set forth in SEQ ID NO: 409. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 72, and the sense strand comprises a sequence as set forth in SEQ ID NO: 410. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 73, and the sense strand comprises a sequence as set forth in SEQ ID NO: 411. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 74, and the sense strand comprises a sequence as set forth in SEQ ID NO: 412. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 75, and the sense strand comprises a sequence as set forth in SEQ ID NO: 413. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 76, and the sense strand comprises a sequence as set forth in SEQ ID NO: 414. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 77, and the sense strand comprises a sequence as set forth in SEQ ID NO: 415. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 78, and the sense strand comprises a sequence as set forth in SEQ ID NO: 416. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 79, and the sense strand comprises a sequence as set forth in SEQ ID NO: 417. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 80, and the sense strand comprises a sequence as set forth in SEQ ID NO: 418. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 81, and the sense strand comprises a sequence as set forth in SEQ ID NO: 419. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 82, and the sense strand comprises a sequence as set forth in SEQ ID NO: 420. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 83, and the sense strand comprises a sequence as set forth in SEQ ID NO: 421. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 84, and the sense strand comprises a sequence as set forth in SEQ ID NO: 422. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 85, and the sense strand comprises a sequence as set forth in SEQ ID NO: 423. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 86, and the sense strand comprises a sequence as set forth in SEQ ID NO: 424. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 87, and the sense strand comprises a sequence as set forth in SEQ ID NO: 425. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 88, and the sense strand comprises a sequence as set forth in SEQ ID NO: 426. In embodiments, the antisense strand comprises a sequence asDB1 / 167456146.4 93Attorney Docket No.: CTY-003PC / 139872-5003set forth in SEQ ID NO: 89, and the sense strand comprises a sequence as set forth in SEQ ID NO: 427. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 90, and the sense strand comprises a sequence as set forth in SEQ ID NO: 428. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 91, and the sense strand comprises a sequence as set forth in SEQ ID NO: 429. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 92, and the sense strand comprises a sequence as set forth in SEQ ID NO: 430. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 93, and the sense strand comprises a sequence as set forth in SEQ ID NO: 431. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 94, and the sense strand comprises a sequence as set forth in SEQ ID NO: 432. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 95, and the sense strand comprises a sequence as set forth in SEQ ID NO: 433. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 96, and the sense strand comprises a sequence as set forth in SEQ ID NO: 434. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 97, and the sense strand comprises a sequence as set forth in SEQ ID NO: 435. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 98, and the sense strand comprises a sequence as set forth in SEQ ID NO: 436. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 99, and the sense strand comprises a sequence as set forth in SEQ ID NO: 437. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 100, and the sense strand comprises a sequence as set forth in SEQ ID NO: 438. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 101, and the sense strand comprises a sequence as set forth in SEQ ID NO: 439. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 102, and the sense strand comprises a sequence as set forth in SEQ ID NO: 440. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 103, and the sense strand comprises a sequence as set forth in SEQ ID NO: 441. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 104, and the sense strand comprises a sequence as set forth in SEQ ID NO: 442. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 105, and the sense strand comprises a sequence as set forth in SEQ ID NO: 443. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 106, and the sense strand comprises a sequence as set forth in SEQ ID NO: 444. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 107, and the sense strand comprises a sequence as set forth in SEQ ID NO: 445. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 108, and the sense strand comprisesDB1 / 167456146.4 94Attorney Docket No.: CTY-003PC / 139872-5003a sequence as set forth in SEQ ID NO: 446. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 109, and the sense strand comprises a sequence as set forth in SEQ ID NO: 447. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 110, and the sense strand comprises a sequence as set forth in SEQ ID NO: 448. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 111, and the sense strand comprises a sequence as set forth in SEQ ID NO: 449. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 112, and the sense strand comprises a sequence as set forth in SEQ ID NO: 450. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 113, and the sense strand comprises a sequence as set forth in SEQ ID NO: 451. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 114, and the sense strand comprises a sequence as set forth in SEQ ID NO: 452. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 115, and the sense strand comprises a sequence as set forth in SEQ ID NO: 453. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 116, and the sense strand comprises a sequence as set forth in SEQ ID NO: 454. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 117, and the sense strand comprises a sequence as set forth in SEQ ID NO: 455. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 118, and the sense strand comprises a sequence as set forth in SEQ ID NO: 456. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 119, and the sense strand comprises a sequence as set forth in SEQ ID NO: 457. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 120, and the sense strand comprises a sequence as set forth in SEQ ID NO: 458. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 121, and the sense strand comprises a sequence as set forth in SEQ ID NO: 459. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 122, and the sense strand comprises a sequence as set forth in SEQ ID NO: 460. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 123, and the sense strand comprises a sequence as set forth in SEQ ID NO: 461. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 124, and the sense strand comprises a sequence as set forth in SEQ ID NO: 462. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 125, and the sense strand comprises a sequence as set forth in SEQ ID NO: 463. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 126, and the sense strand comprises a sequence as set forth in SEQ ID NO: 464. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 127, and the sense strand comprises a sequence as set forth in SEQ ID NO: 465. In embodiments,DB1 / 167456146.4 95Attorney Docket No.: CTY-003PC / 139872-5003the antisense strand comprises a sequence as set forth in SEQ ID NO: 128, and the sense strand comprises a sequence as set forth in SEQ ID NO: 466. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 129, and the sense strand comprises a sequence as set forth in SEQ ID NO: 467. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 130, and the sense strand comprises a sequence as set forth in SEQ ID NO: 468. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 131, and the sense strand comprises a sequence as set forth in SEQ ID NO: 469. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 132, and the sense strand comprises a sequence as set forth in SEQ ID NO: 470. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 133, and the sense strand comprises a sequence as set forth in SEQ ID NO: 471. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 134, and the sense strand comprises a sequence as set forth in SEQ ID NO: 472. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 135, and the sense strand comprises a sequence as set forth in SEQ ID NO: 473. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 136, and the sense strand comprises a sequence as set forth in SEQ ID NO: 474. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 137, and the sense strand comprises a sequence as set forth in SEQ ID NO: 475. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 138, and the sense strand comprises a sequence as set forth in SEQ ID NO: 476. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 139, and the sense strand comprises a sequence as set forth in SEQ ID NO: 477. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 140, and the sense strand comprises a sequence as set forth in SEQ ID NO: 478. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 141, and the sense strand comprises a sequence as set forth in SEQ ID NO: 479. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 142, and the sense strand comprises a sequence as set forth in SEQ ID NO: 480. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 143, and the sense strand comprises a sequence as set forth in SEQ ID NO: 481. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 144, and the sense strand comprises a sequence as set forth in SEQ ID NO: 482. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 145, and the sense strand comprises a sequence as set forth in SEQ ID NO: 483. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 146, and the sense strand comprises a sequence as set forth in SEQ ID NO: 484. In embodiments, the antisense strand comprises a sequence as set forth in SEQDB1 / 167456146.4 96Attorney Docket No.: CTY-003PC / 139872-5003ID NO: 147, and the sense strand comprises a sequence as set forth in SEQ ID NO: 485. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 148, and the sense strand comprises a sequence as set forth in SEQ ID NO: 486. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 149, and the sense strand comprises a sequence as set forth in SEQ ID NO: 487. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 150, and the sense strand comprises a sequence as set forth in SEQ ID NO: 488. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 151, and the sense strand comprises a sequence as set forth in SEQ ID NO: 489. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 152, and the sense strand comprises a sequence as set forth in SEQ ID NO: 490. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 153, and the sense strand comprises a sequence as set forth in SEQ ID NO: 491. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 154, and the sense strand comprises a sequence as set forth in SEQ ID NO: 492. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 155, and the sense strand comprises a sequence as set forth in SEQ ID NO: 493. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 156, and the sense strand comprises a sequence as set forth in SEQ ID NO: 494. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 157, and the sense strand comprises a sequence as set forth in SEQ ID NO: 495. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 158, and the sense strand comprises a sequence as set forth in SEQ ID NO: 496. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 159, and the sense strand comprises a sequence as set forth in SEQ ID NO: 497. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 160, and the sense strand comprises a sequence as set forth in SEQ ID NO: 498. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 161, and the sense strand comprises a sequence as set forth in SEQ ID NO: 499. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 162, and the sense strand comprises a sequence as set forth in SEQ ID NO: 500. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 163, and the sense strand comprises a sequence as set forth in SEQ ID NO: 501. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 164, and the sense strand comprises a sequence as set forth in SEQ ID NO: 502. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 165, and the sense strand comprises a sequence as set forth in SEQ ID NO: 503. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 166, and the sense strand comprises a sequence as setDB1 / 167456146.4 97Attorney Docket No.: CTY-003PC / 139872-5003forth in SEQ ID NO: 504. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 167, and the sense strand comprises a sequence as set forth in SEQ ID NO: 505. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 168, and the sense strand comprises a sequence as set forth in SEQ ID NO: 506. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 169, and the sense strand comprises a sequence as set forth in SEQ ID NO: 507. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 170, and the sense strand comprises a sequence as set forth in SEQ ID NO: 508. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 171, and the sense strand comprises a sequence as set forth in SEQ ID NO: 509. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 172, and the sense strand comprises a sequence as set forth in SEQ ID NO: 510. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 173, and the sense strand comprises a sequence as set forth in SEQ ID NO: 511. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 174, and the sense strand comprises a sequence as set forth in SEQ ID NO: 512. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 175, and the sense strand comprises a sequence as set forth in SEQ ID NO: 513. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 176, and the sense strand comprises a sequence as set forth in SEQ ID NO: 514. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 177, and the sense strand comprises a sequence as set forth in SEQ ID NO: 515. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 178, and the sense strand comprises a sequence as set forth in SEQ ID NO: 516. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 179, and the sense strand comprises a sequence as set forth in SEQ ID NO: 517. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 180, and the sense strand comprises a sequence as set forth in SEQ ID NO: 518. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 181, and the sense strand comprises a sequence as set forth in SEQ ID NO: 519. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 182, and the sense strand comprises a sequence as set forth in SEQ ID NO: 520. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 183, and the sense strand comprises a sequence as set forth in SEQ ID NO: 521. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 184, and the sense strand comprises a sequence as set forth in SEQ ID NO: 522. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 185, and the sense strand comprises a sequence as set forth in SEQ ID NO: 523. In embodiments, the antisense strandDB1 / 167456146.4 98Attorney Docket No.: CTY-003PC / 139872-5003comprises a sequence as set forth in SEQ ID NO: 186, and the sense strand comprises a sequence as set forth in SEQ ID NO: 524. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 187, and the sense strand comprises a sequence as set forth in SEQ ID NO: 525. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 188, and the sense strand comprises a sequence as set forth in SEQ ID NO: 526. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 189, and the sense strand comprises a sequence as set forth in SEQ ID NO: 527. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 190, and the sense strand comprises a sequence as set forth in SEQ ID NO: 528. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 191, and the sense strand comprises a sequence as set forth in SEQ ID NO: 529. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 192, and the sense strand comprises a sequence as set forth in SEQ ID NO: 530. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 193, and the sense strand comprises a sequence as set forth in SEQ ID NO: 531. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 194, and the sense strand comprises a sequence as set forth in SEQ ID NO: 532. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 195, and the sense strand comprises a sequence as set forth in SEQ ID NO: 533. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 196, and the sense strand comprises a sequence as set forth in SEQ ID NO: 534. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 197, and the sense strand comprises a sequence as set forth in SEQ ID NO: 535. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 198, and the sense strand comprises a sequence as set forth in SEQ ID NO: 536. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 199, and the sense strand comprises a sequence as set forth in SEQ ID NO: 537. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 200, and the sense strand comprises a sequence as set forth in SEQ ID NO: 538. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 201, and the sense strand comprises a sequence as set forth in SEQ ID NO: 539. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 202, and the sense strand comprises a sequence as set forth in SEQ ID NO: 540. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 203, and the sense strand comprises a sequence as set forth in SEQ ID NO: 541. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 204, and the sense strand comprises a sequence as set forth in SEQ ID NO: 542. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 205, and the senseDB1 / 167456146.4 99Attorney Docket No.: CTY-003PC / 139872-5003strand comprises a sequence as set forth in SEQ ID NO: 543. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 206, and the sense strand comprises a sequence as set forth in SEQ ID NO: 544. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 207, and the sense strand comprises a sequence as set forth in SEQ ID NO: 545. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 208, and the sense strand comprises a sequence as set forth in SEQ ID NO: 546. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 209, and the sense strand comprises a sequence as set forth in SEQ ID NO: 547. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 210, and the sense strand comprises a sequence as set forth in SEQ ID NO: 548. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 211, and the sense strand comprises a sequence as set forth in SEQ ID NO: 549. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 212, and the sense strand comprises a sequence as set forth in SEQ ID NO: 550. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 213, and the sense strand comprises a sequence as set forth in SEQ ID NO: 551. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 214, and the sense strand comprises a sequence as set forth in SEQ ID NO: 552. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 215, and the sense strand comprises a sequence as set forth in SEQ ID NO: 553. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 216, and the sense strand comprises a sequence as set forth in SEQ ID NO: 554. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 217, and the sense strand comprises a sequence as set forth in SEQ ID NO: 555. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 218, and the sense strand comprises a sequence as set forth in SEQ ID NO: 556. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 219, and the sense strand comprises a sequence as set forth in SEQ ID NO: 557. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 220, and the sense strand comprises a sequence as set forth in SEQ ID NO: 558. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 221, and the sense strand comprises a sequence as set forth in SEQ ID NO: 559. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 222, and the sense strand comprises a sequence as set forth in SEQ ID NO: 560. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 223, and the sense strand comprises a sequence as set forth in SEQ ID NO: 561. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 224, and the sense strand comprises a sequence as set forth in SEQ ID NO: 562. InDB1 / 167456146.4 100Attorney Docket No.: CTY-003PC / 139872-5003embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 225, and the sense strand comprises a sequence as set forth in SEQ ID NO: 563. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 226, and the sense strand comprises a sequence as set forth in SEQ ID NO: 564. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 227, and the sense strand comprises a sequence as set forth in SEQ ID NO: 565. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 228, and the sense strand comprises a sequence as set forth in SEQ ID NO: 566. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 229, and the sense strand comprises a sequence as set forth in SEQ ID NO: 567. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 230, and the sense strand comprises a sequence as set forth in SEQ ID NO: 568. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 231, and the sense strand comprises a sequence as set forth in SEQ ID NO: 569. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 232, and the sense strand comprises a sequence as set forth in SEQ ID NO: 570. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 233, and the sense strand comprises a sequence as set forth in SEQ ID NO: 571. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 234, and the sense strand comprises a sequence as set forth in SEQ ID NO: 572. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 235, and the sense strand comprises a sequence as set forth in SEQ ID NO: 573. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 236, and the sense strand comprises a sequence as set forth in SEQ ID NO: 574. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 237, and the sense strand comprises a sequence as set forth in SEQ ID NO: 575. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 238, and the sense strand comprises a sequence as set forth in SEQ ID NO: 576. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 239, and the sense strand comprises a sequence as set forth in SEQ ID NO: 577. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 240, and the sense strand comprises a sequence as set forth in SEQ ID NO: 578. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 241, and the sense strand comprises a sequence as set forth in SEQ ID NO: 579. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 242, and the sense strand comprises a sequence as set forth in SEQ ID NO: 580. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 243, and the sense strand comprises a sequence as set forth in SEQ ID NO: 581. In embodiments, the antisense strand comprises a sequence asDB1 / 167456146.4 101Attorney Docket No.: CTY-003PC / 139872-5003set forth in SEQ ID NO: 244, and the sense strand comprises a sequence as set forth in SEQ ID NO: 582. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 245, and the sense strand comprises a sequence as set forth in SEQ ID NO: 583. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 246, and the sense strand comprises a sequence as set forth in SEQ ID NO: 584. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 247, and the sense strand comprises a sequence as set forth in SEQ ID NO: 585. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 248, and the sense strand comprises a sequence as set forth in SEQ ID NO: 586. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 249, and the sense strand comprises a sequence as set forth in SEQ ID NO: 587. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 250, and the sense strand comprises a sequence as set forth in SEQ ID NO: 588. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 251, and the sense strand comprises a sequence as set forth in SEQ ID NO: 589. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 252, and the sense strand comprises a sequence as set forth in SEQ ID NO: 590. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 253, and the sense strand comprises a sequence as set forth in SEQ ID NO: 591. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 254, and the sense strand comprises a sequence as set forth in SEQ ID NO: 592. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 255, and the sense strand comprises a sequence as set forth in SEQ ID NO: 593. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 256, and the sense strand comprises a sequence as set forth in SEQ ID NO: 594. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 257, and the sense strand comprises a sequence as set forth in SEQ ID NO: 595. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 258, and the sense strand comprises a sequence as set forth in SEQ ID NO: 596. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 259, and the sense strand comprises a sequence as set forth in SEQ ID NO: 597. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 260, and the sense strand comprises a sequence as set forth in SEQ ID NO: 598. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 261, and the sense strand comprises a sequence as set forth in SEQ ID NO: 599. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 262, and the sense strand comprises a sequence as set forth in SEQ ID NO: 600. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 263, and the sense strand comprisesDB1 / 167456146.4 102Attorney Docket No.: CTY-003PC / 139872-5003a sequence as set forth in SEQ ID NO: 601. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 264, and the sense strand comprises a sequence as set forth in SEQ ID NO: 602. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 265, and the sense strand comprises a sequence as set forth in SEQ ID NO: 603. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 266, and the sense strand comprises a sequence as set forth in SEQ ID NO: 604. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 267, and the sense strand comprises a sequence as set forth in SEQ ID NO: 605. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 268, and the sense strand comprises a sequence as set forth in SEQ ID NO: 606. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 269, and the sense strand comprises a sequence as set forth in SEQ ID NO: 607. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 270, and the sense strand comprises a sequence as set forth in SEQ ID NO: 608. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 271, and the sense strand comprises a sequence as set forth in SEQ ID NO: 609. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 272, and the sense strand comprises a sequence as set forth in SEQ ID NO: 610. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 273, and the sense strand comprises a sequence as set forth in SEQ ID NO: 611. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 274, and the sense strand comprises a sequence as set forth in SEQ ID NO: 612. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 275, and the sense strand comprises a sequence as set forth in SEQ ID NO: 613. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 276, and the sense strand comprises a sequence as set forth in SEQ ID NO: 614. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 277, and the sense strand comprises a sequence as set forth in SEQ ID NO: 615. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 278, and the sense strand comprises a sequence as set forth in SEQ ID NO: 616. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 279, and the sense strand comprises a sequence as set forth in SEQ ID NO: 617. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 280, and the sense strand comprises a sequence as set forth in SEQ ID NO: 618. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 281, and the sense strand comprises a sequence as set forth in SEQ ID NO: 619. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 282, and the sense strand comprises a sequence as set forth in SEQ ID NO: 620. In embodiments,DB1 / 167456146.4 103Attorney Docket No.: CTY-003PC / 139872-5003the antisense strand comprises a sequence as set forth in SEQ ID NO: 283, and the sense strand comprises a sequence as set forth in SEQ ID NO: 621. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 284, and the sense strand comprises a sequence as set forth in SEQ ID NO: 622. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 285, and the sense strand comprises a sequence as set forth in SEQ ID NO: 623. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 286, and the sense strand comprises a sequence as set forth in SEQ ID NO: 624. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 287, and the sense strand comprises a sequence as set forth in SEQ ID NO: 625. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 288, and the sense strand comprises a sequence as set forth in SEQ ID NO: 626. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 289, and the sense strand comprises a sequence as set forth in SEQ ID NO: 627. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 290, and the sense strand comprises a sequence as set forth in SEQ ID NO: 628. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 291, and the sense strand comprises a sequence as set forth in SEQ ID NO: 629. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 292, and the sense strand comprises a sequence as set forth in SEQ ID NO: 630. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 293, and the sense strand comprises a sequence as set forth in SEQ ID NO: 631. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 294, and the sense strand comprises a sequence as set forth in SEQ ID NO: 632. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 295, and the sense strand comprises a sequence as set forth in SEQ ID NO: 633. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 296, and the sense strand comprises a sequence as set forth in SEQ ID NO: 634. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 297, and the sense strand comprises a sequence as set forth in SEQ ID NO: 635. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 298, and the sense strand comprises a sequence as set forth in SEQ ID NO: 636. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 299, and the sense strand comprises a sequence as set forth in SEQ ID NO: 637. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 300, and the sense strand comprises a sequence as set forth in SEQ ID NO: 638. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 301, and the sense strand comprises a sequence as set forth in SEQ ID NO: 639. In embodiments, the antisense strand comprises a sequence as set forth in SEQDB1 / 167456146.4 104Attorney Docket No.: CTY-003PC / 139872-5003ID NO: 302, and the sense strand comprises a sequence as set forth in SEQ ID NO: 640. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 303, and the sense strand comprises a sequence as set forth in SEQ ID NO: 641. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 304, and the sense strand comprises a sequence as set forth in SEQ ID NO: 642. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 305, and the sense strand comprises a sequence as set forth in SEQ ID NO: 643. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 306, and the sense strand comprises a sequence as set forth in SEQ ID NO: 644. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 307, and the sense strand comprises a sequence as set forth in SEQ ID NO: 645. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 308, and the sense strand comprises a sequence as set forth in SEQ ID NO: 646. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 309, and the sense strand comprises a sequence as set forth in SEQ ID NO: 647. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 310, and the sense strand comprises a sequence as set forth in SEQ ID NO: 648. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 311, and the sense strand comprises a sequence as set forth in SEQ ID NO: 649. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 312, and the sense strand comprises a sequence as set forth in SEQ ID NO: 650. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 313, and the sense strand comprises a sequence as set forth in SEQ ID NO: 651. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 314, and the sense strand comprises a sequence as set forth in SEQ ID NO: 652. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 315, and the sense strand comprises a sequence as set forth in SEQ ID NO: 653. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 316, and the sense strand comprises a sequence as set forth in SEQ ID NO: 654. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 317, and the sense strand comprises a sequence as set forth in SEQ ID NO: 655. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 318, and the sense strand comprises a sequence as set forth in SEQ ID NO: 656. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 319, and the sense strand comprises a sequence as set forth in SEQ ID NO: 657. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 320, and the sense strand comprises a sequence as set forth in SEQ ID NO: 658. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 321, and the sense strand comprises a sequence as setDB1 / 167456146.4 105Attorney Docket No.: CTY-003PC / 139872-5003forth in SEQ ID NO: 659. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 322, and the sense strand comprises a sequence as set forth in SEQ ID NO: 660. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 323, and the sense strand comprises a sequence as set forth in SEQ ID NO: 661. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 324, and the sense strand comprises a sequence as set forth in SEQ ID NO: 662. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 325, and the sense strand comprises a sequence as set forth in SEQ ID NO: 663. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 326, and the sense strand comprises a sequence as set forth in SEQ ID NO: 664. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 327, and the sense strand comprises a sequence as set forth in SEQ ID NO: 665. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 328, and the sense strand comprises a sequence as set forth in SEQ ID NO: 666. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 329, and the sense strand comprises a sequence as set forth in SEQ ID NO: 667. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 330, and the sense strand comprises a sequence as set forth in SEQ ID NO: 668. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 331, and the sense strand comprises a sequence as set forth in SEQ ID NO: 669. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 332, and the sense strand comprises a sequence as set forth in SEQ ID NO: 670. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 333, and the sense strand comprises a sequence as set forth in SEQ ID NO: 671. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 334, and the sense strand comprises a sequence as set forth in SEQ ID NO: 672. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 335, and the sense strand comprises a sequence as set forth in SEQ ID NO: 673. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 336, and the sense strand comprises a sequence as set forth in SEQ ID NO: 674. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 337, and the sense strand comprises a sequence as set forth in SEQ ID NO: 675. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 338, and the sense strand comprises a sequence as set forth in SEQ ID NO: 676.In embodiments, the RNAi agent provided herein is or comprises one or more of Duplex4178UM, Duplex4181 UM, Duplex4128UM, Duplex4026UM, Duplex3336UM, Duplex4125UM, and Duplex3391UM. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 323, and the senseDB1 / 167456146.4 106Attorney Docket No.: CTY-003PC / 139872-5003strand comprises a sequence as set forth in SEQ ID NO: 661. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 326, and the sense strand comprises a sequence as set forth in SEQ ID NO: 664. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 310, and the sense strand comprises a sequence as set forth in SEQ ID NO: 648. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 275, and the sense strand comprises a sequence as set forth in SEQ ID NO: 613. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 29, and the sense strand comprises a sequence as set forth in SEQ ID NO: 367. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 307, and the sense strand comprises a sequence as set forth in SEQ ID NO: 645. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 53, and the sense strand comprises a sequence as set forth in SEQ ID NO: 391.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 323, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 661.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 326, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 664.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 310, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 648.DB1 / 167456146.4 107Attorney Docket No.: CTY-003PC / 139872-5003In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 275, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 613.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 29, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 367.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 307, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 645.In aspects, the disclosure provides a double stranded ribonucleic acid interference agent (RNAi agent), wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the antisense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 53, and the sense strand comprises a region of complementarity which comprises at least 12 contiguous nucleotides differing by no more than 3 nucleotides from a sequence as set forth in SEQ ID NO: 391.In embodiments, the RNAi agent provided herein comprises a sense strand comprising a sequence and chemical modifications as set forth in any one of SEQ ID NOs: 1015-1352 and an antisense strand comprising a complementary sequence and chemical modifications selected from SEQ ID NOs: 1353-1690, as is also arranged in Table 2, including modifications to the sense sequence and antisense sequences. In embodiments, the RNAi agent provided herein comprises a sense strand comprising a sequence and chemical modifications as set forth in any one of SEQ ID NOs: 1696-1715 and an antisense strand comprisingDB1 / 167456146.4 108Attorney Docket No.: CTY-003PC / 139872-5003a complementary sequence and chemical modifications selected from SEQ ID NOs: 1716-1735, as is also arranged in Table 3. In embodiments, the RNAi agent provided herein comprises a sense strand comprising a sequence and chemical modifications as set forth in any one of SEQ ID NOs: 1736-1758 and an antisense strand comprising a complementary sequence and chemical modifications selected from SEQ ID NOs: 1759- 1781, as is also arranged in Table 4.In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1353, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1015. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1354, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1016. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1355, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1017. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1356, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1018. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1357, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1019. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1358, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1020. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1359, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1021. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1360, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1022. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1361, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1023. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1362, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1024. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1363, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1025. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1364, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1026. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1365, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1027. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1366, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1028. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1367, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1029. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1368, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1030. InDB1 / 167456146.4 109Attorney Docket No.: CTY-003PC / 139872-5003embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1369, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1031. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1370, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1032. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1371, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1033. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1372, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1034. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1373, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1035. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1374, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1036. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1375, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1037. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1376, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1038. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1377, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1039. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1378, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1040. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1379, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1041. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1380, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1042. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1381, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1043. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1382, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1044. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1383, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1045. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1384, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1046. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1385, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1047. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1386, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1048. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1387, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1049. In embodiments,DB1 / 167456146.4 110Attorney Docket No.: CTY-003PC / 139872-5003the antisense strand comprises a sequence as set forth in SEQ ID NO: 1388, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1050. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1389, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1051. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1390, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1052. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1391, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1053. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1392, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1054. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1393, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1055. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1394, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1056. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1395, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1057. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1396, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1058. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1397, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1059. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1398, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1060. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1399, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1061. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1400, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1062. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1401, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1063. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1402, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1064. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1403, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1065. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1404, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1066. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1405, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1067. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1406, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1068. In embodiments, the antisenseDB1 / 167456146.4 111Attorney Docket No.: CTY-003PC / 139872-5003strand comprises a sequence as set forth in SEQ ID NO: 1407, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1069. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1408, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1070. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1409, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1071. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1410, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1072. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1411, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1073. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1412, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1074. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1413, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1075. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1414, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1076. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1415, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1077. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1416, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1078. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1417, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1079. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1418, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1080. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1419, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1081. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1420, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1082. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1421, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1083. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1422, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1084. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1423, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1085. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1424, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1086. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1425, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1087. In embodiments, the antisense strandDB1 / 167456146.4 112Attorney Docket No.: CTY-003PC / 139872-5003comprises a sequence as set forth in SEQ ID NO: 1426, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1088. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1427, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1089. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1428, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1090. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1429, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1091. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1430, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1092. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1431, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1093. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1432, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1094. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1433, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1095. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1434, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1096. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1435, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1097. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1436, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1098. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1437, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1099. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1438, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1100. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1439, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1101. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1440, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1102. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1441, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1103. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1442, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1104. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1443, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1105. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1444, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1106. In embodiments, the antisense strand comprises a sequenceDB1 / 167456146.4 113Attorney Docket No.: CTY-003PC / 139872-5003as set forth in SEQ ID NO: 1445, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1107. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1446, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1108. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1447, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1109. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1448, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1110. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1449, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1111. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1450, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1112. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1451, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1113. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1452, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1114. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1453, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1115. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1454, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1116. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1455, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1117. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1456, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1118. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1457, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1119. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1458, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1120. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1459, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1121. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1460, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1122. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1461, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1123. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1462, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1124. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1463, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1125. In embodiments, the antisense strand comprises a sequence as set forthDB1 / 167456146.4 114Attorney Docket No.: CTY-003PC / 139872-5003in SEQ ID NO: 1464, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1126. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1465, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1127. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1466, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1128. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1467, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1129. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1468, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1130. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1469, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1131. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1470, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1132. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1471, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1133. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1472, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1134. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1473, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1135. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1474, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1136. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1475, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1137. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1476, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1138. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1477, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1139. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1478, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1140. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1479, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1141. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1480, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1142. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1481, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1143. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1482, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1144. In embodiments, the antisense strand comprises a sequence as set forth in SEQDB1 / 167456146.4 115Attorney Docket No.: CTY-003PC / 139872-5003ID NO: 1483, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1145. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1484, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1146. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1485, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1147. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1486, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1148. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1487, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1149. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1488, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1150. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1489, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1151. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1490, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1152. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1491, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1153. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1492, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1154. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1493, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1155. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1494, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1156. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1495, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1157. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1496, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1158. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1497, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1159. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1498, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1160. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1499, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1161. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1500, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1162. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1501, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1163. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1502, andDB1 / 167456146.4 116Attorney Docket No.: CTY-003PC / 139872-5003the sense strand comprises a sequence as set forth in SEQ ID NO: 1164. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1503, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1165. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1504, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1166. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1505, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1167. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1506, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1168. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1507, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1169. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1508, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1170. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1509, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1171. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1510, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1172. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1511, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1173. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1512, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1174. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1513, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1175. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1514, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1176. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1515, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1177. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1516, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1178. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1517, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1179. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1518, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1180. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1519, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1181. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1520, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1182. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1521, and the senseDB1 / 167456146.4 117Attorney Docket No.: CTY-003PC / 139872-5003strand comprises a sequence as set forth in SEQ ID NO: 1183. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1522, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1184. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1523, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1185. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1524, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1186. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1525, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1187. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1526, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1188. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1527, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1189. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1528, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1190. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1529, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1191. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1530, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1192. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1531, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1193. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1532, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1194. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1533, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1195. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1534, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1196. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1535, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1197. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1536, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1198. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1537, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1199. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1538, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1200. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1539, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1201. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1540, and the sense strand comprisesDB1 / 167456146.4 118Attorney Docket No.: CTY-003PC / 139872-5003a sequence as set forth in SEQ ID NO: 1202. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1541, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1203. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1542, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1204. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1543, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1205. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1544, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1206. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1545, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1207. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1546, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1208. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1547, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1209. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1548, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1210. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1549, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1211. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1550, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1212. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1551, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1213. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1552, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1214. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1553, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1215. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1554, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1216. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1555, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1217. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1556, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1218. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1557, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1219. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1558, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1220. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1559, and the sense strand comprises a sequenceDB1 / 167456146.4 119Attorney Docket No.: CTY-003PC / 139872-5003as set forth in SEQ ID NO: 1221. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1560, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1222. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1561, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1223. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1562, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1224. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1563, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1225. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1564, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1226. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1565, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1227. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1566, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1228. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1567, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1229. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1568, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1230. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1569, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1231. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1570, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1232. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1571, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1233. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1572, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1234. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1573, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1235. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1574, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1236. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1575, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1237. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1576, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1238. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1577, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1239. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1578, and the sense strand comprises a sequence as setDB1 / 167456146.4 120Attorney Docket No.: CTY-003PC / 139872-5003forth in SEQ ID NO: 1240. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1579, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1241. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1580, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1242. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1581, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1243. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1582, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1244. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1583, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1245. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1584, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1246. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1585, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1247. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1586, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1248. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1587, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1249. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1588, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1250. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1589, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1251. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1590, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1252. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1591, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1253. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1592, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1254. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1593, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1255. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1594, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1256. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1595, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1257. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1596, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1258. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1597, and the sense strand comprises a sequence as set forth in SEQ ID NO:DB1 / 167456146.4 121Attorney Docket No.: CTY-003PC / 139872-50031259. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1598, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1260. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1599, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1261. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1600, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1262. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1601, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1263. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1602, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1264. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1603, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1265. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1604, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1266. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1605, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1267. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1606, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1268. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1607, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1269. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1608, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1270. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1609, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1271. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1610, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1272. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1611, and the sense strand comprises a sequence as set forth in SEQ ID NO: 1273. In embodiments, the antisense strand comprises a sequence as set forth in SEQ ID NO: 1612, and the sense strand comprises a sequence as set forth in SEQ ID NO...

Claims

1. Attorney Docket No.: CTY-003PC / 139872-5003CLAIMSWhat is claimed is:

1. A double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, and wherein said antisense strand comprises a region of complementarity which comprises at least 12, or at least 13, or at least 14 contiguous nucleotides differing by no more than 3 nucleotides from a nucleotide sequence selected from any one of the antisense strands listed in Table 2, Table 1, Table 3, Table4, Table 5, orTable 6, optionally wherein the RNAi agent comprises at least one chemical modification selected from internucleotide linkage modification, sugar modifications, base modifications, 5’-end modification, reversible modification, and a combination thereof.

2. A double stranded ribonucleic acid interference agent (RNAi agent), wherein said RNAi agent comprises a sense strand and an antisense strand, wherein said sense strand and said antisense strand comprises a region of complementarity which comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from any one of the duplexes listed in Table 2, Table 1, Table 3, Table 4, Table 5, or Table 6, optionally wherein the RNAi agent comprises at least one chemical modification selected from internucleotide linkage modification, sugar modifications, base modifications, 5'-end modification, reversible modification, and a combination thereof.

3. The RNAi agent of claim 1 or claim 2, wherein at least one of the sense strand and the antisense strand comprises a targeting ligand.

4. The RNAi agent of claim 3, wherein the targeting ligand targets a receptor which mediates delivery to a liver tissue.

5. The RNAi agent of claim 3 or claim 4, wherein the targeting ligand enhances hepatocyte cell delivery of the RNAi agent compared to the delivery in the absence of the targeting ligand compared to the delivery in the absence of the targeting ligand.

6. The RNAi agent of any one of claims 3-5, wherein the targeting ligand binds the Asialoglycoprotein receptor (ASGPR) on hepatocyte cells, and is optionally selected from a GalNAc moiety, a galactosylated cholesterol, a glycolipid, an arabinogalactan (AG), bicyclic bridged ketal, and lactosylated / galactosylated moiety.DB1 / 167456146.4 373Attorney Docket No.: CTY-003PC / 139872-50037. The RNAi agent of any one of claims 3-6, wherein the targeting ligand is one or more GalNAc moieties attached through a bivalent or trivalent branched linker.

8. The RNAi agent of any one of claims 3-7, wherein the ligand is attached to the 3’ end, the 5’ end, or the 3’ and 5’ end of the sense strand.

9. The RNAi agent of any one of claims 3-8, wherein the targeting ligand is a triantennary GalNAc ligand.

10. The RNAi agent of any one of claims 3-9, wherein the targeting ligand is attached to the RNAi agent at the 3’-terminal nucleotide residue of the sense strand.

11. The RNAi agent of any one of claims 3-10, wherein the targeting ligand comprises a structure selected from:o, o- 'pz5-ohgo O' " OAcHNDB1 / 167456146.4 374Attorney Docket No.: CTY-003PC / 139872-5003DB1 / 167456146.4 375Attorney Docket No.: CTY-003PC / 139872-5003DB1 / 167456146.4 376Attorney Docket No.: CTY-003PC / 139872-500312. The RNAi agent of any one of claims 3-11, wherein the targeting ligand is conjugated via a bio- cleavable linker selected from DNA, RNA, disulfide, amide, functionalized monosaccharides or oligosaccharides of galactosamine, glucosamine, glucose, galactose, mannose, and combinations thereof.

13. The RNAi agent of any one of claims 1-12, wherein the sense strand comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of the sense strand nucleotide sequence of a chemically modified duplex selected from SEQ ID NOs: 1015-1352, 1696- 1715 and 1736-1758.

14. The RNAi agent of any one of claims 1-13, wherein the antisense strand comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from the antisense nucleotide sequence of a chemically modified duplex selected from SEQ ID NOs: 1353-1690, 1716-1735, and 1759-1781.

15. The RNAi agent of any one of claims 1-14, wherein:at least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the sense strand are modified nucleotides; and / orat least 2, or at least 3, or at least 4, or at least 5, or at least 6, or at least 7, or at least 8, or at least 9, or at least 10, or at least 11, or at least 12, or at least 13, or at least 14, or at least 15, or at least 16, or more of the nucleotides of the antisense strand are modified nucleotides.

16. The RNAi agent of any of one of claims 1-15, wherein all of the nucleotides of the sense strand and / or the antisense strand are modified nucleotides.

17. The RNAi agent of claim 15 or claim 16, wherein at least one of the modified nucleotides comprise nucleotide modifications selected from sugar modifications, internucleotide linkage modification ( / .e., backbone modifications), nucleobase modifications, 5’-end modification, 3’ -end modification, conjugation with a targeting moiety and a combination thereof.

18. The RNAi agent of claim 17, wherein the nucleotide modifications are selected from a 2’-O-methyl modified nucleotide, a 2’-fluoro modified nucleotide, a deoxy-nucleotide, a 3’-terminal deoxy-thymine (dT) nucleotide, a 2’-deoxy-modified nucleotide, a locked nucleotide, an unlocked nucleotide, a conformationally restricted nucleotide, a constrained ethyl nucleotide, an abasic nucleotide, a T-ami no-modified nucleotide, a 2’-O-allyl-modified nucleotide, 2’-C-alkyl-modified nucleotide, 2’-hydroxyl-modified nucleotide, a 2’- DB1 / 167456146.4 377Attorney Docket No.: CTY-003PC / 139872-5003methoxyethyl modified nucleotide, a 2’-O-alkyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a tetrahydropyran modified nucleotide, a 1,5- anhydrohexitol modified nucleotide, a cyclohexenyl modified nucleotide, a 2’-deoxy-2’-fluoro modified nucleotide, a 2’-deoxy modified nucleotide, 3’-terminal deoxy-thymine nucleotides (dT), a locked nucleotide, an abasic nucleotide, a 2’-amino-modified nucleotide, a 2’-al kyl-modified nucleotide, a morpholino nucleotide, a phosphoramidate, a non-natural base comprising nucleotide, a nucleotide comprising a 5’- phosphorothioate group, a nucleotide comprising a 5’-methylphosphonate group, a nucleotide comprising a 5’ phosphate or 5’ phosphate mimic, a nucleotide comprising vinyl phosphonate, a nucleotide comprising adenosine-glycol nucleic acid (GNA), a nucleotide comprising thymidine-glycol nucleic acid (GNA) S-Isomer, a nucleotide comprising 2-hydroxymethyl-tetrahydrofurane-5-phosphate, a nucleotide comprising 2’- deoxythymidine-3’-phosphate, a nucleotide comprising T-deoxyguanosine-3’-phosphate, and a terminal nucleotide linked to a cholesteryl derivative and a dodecanoic acid bisdecylamide group.

19. The RNAi agent of any one of claims 15-18, further comprising at least one, or at least two, or at least three, or about 6-8 phosphorothioate internucleotide linkages.

20. The RNAi agent of any one of claims 1-19, wherein the region of complementarity is at least 17 nucleotides in length.

21. The RNAi agentof any one of claims 1-20, wherein each strand is no more than about 22 nucleotides in length.

22. The RNAi agent of any one of claims 1-21, wherein the sense strand has a total of 21 nucleotides and the antisense strand has a total of 23 nucleotides, or the sense strand has a total of 19 nucleotides and the antisense strand has a total of 21 nucleotides.

23. The RNAi agent of any one of claims 1-22, wherein at least one strand comprises a 3’ overhang of at least 1 nucleotide.

24. The RNAi agent of any one of claims 1-23, further comprising a phosphate or phosphate mimic at the 5’-end of the antisense strand, optionally wherein the phosphate mimic is a vinyl-phosphonate 2’-OMe- uracil (vinu).DB1 / 167456146.4 378Attorney Docket No.: CTY-003PC / 139872-500325. The RNAi agent of any one of claims 1 -24, wherein the RNAi agent comprises at least 14 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of a duplex selected from Duplex4178 (SEQ ID NOs: 1337 and 1675), Duplex4181 (SEQ ID NOs: 1340 and 1678), Duplex4128 (SEQ ID NOs: 1324 and 1662), Duplex7902 (SEQ ID NOs: 1703 and 1723), Duplex8045 (SEQ ID NOs: 1754 and 1777), Duplex4026 (SEQ ID NOs: 1289 and 1627), Duplex3336 (SEQ ID NOs: 1043 and 1381), Duplex4125 (SEQ ID NOs: 1321 and 1659), Duplex3391 (SEQ ID NOs: 1067 and 1405), Duplex4178UM (SEQ ID NOs: 323 and 661), Duplex4181UM (SEQ ID NOs: 326 and 664), Duplex4128UM (SEQ ID NOs: 310 and 648), Duplex4026UM (SEQ ID NOs: 275 and 613), Duplex3336UM (SEQ ID NOs: 29 and 367), Duplex4125UM (SEQ ID NOs: 307 and 645), and Duplex3391UM (SEQ ID NOs: 53 and 391).

26. The RNAi agent of any one of claims 1-24, wherein:wherein said antisense strand comprises a nucleotide sequence selected from the nucleotide sequence of SEQ ID NOs: 1015-1352, 1-338, 1716-1735, 1759-1781, 1783, 1785, 1787, 1789, 1791, 1793, 1795, 1797, 1799, 1801, 1803, 1805, 1807, 1809, 1811, 1813, 1815, 1817, 1819, 1821, 1823, and 1825; and wherein said sense strand comprises a nucleotide sequence selected from the nucleotide sequence of SEQ ID NOs: 1353-1690, 339-676, 1696-1715, 1736-1758, 1782, 1784, 1786, 1788, 1790, 1792, 1794, 1796, 1798, 1800, 1802, 1804, 1806, 1808, 1810, 1812, 1814, 1816, 1818, 1820, 1822, and 1824, respectively.

27. A cell comprising the RNAi agent of any one of claims 1 -26.

28. A pharmaceutical composition comprising a pharmaceutically acceptable excipient or carrier, and the RNAi agent of any one of claims 1-26.

29. The pharmaceutical composition of claim 28, wherein the RNAi agent is administered or suitable for administration in an unbuffered solution.

30. The pharmaceutical composition of claim 29, wherein said unbuffered solution is saline or water.

31. The pharmaceutical composition of any one of claims 28-30, wherein the pharmaceutical composition comprises the RNAi agent (free acid form) in water for injection at pH of about 7, adjusted with sodium hydroxide and / or phosphoric acid.DB1 / 167456146.4 379Attorney Docket No.: CTY-003PC / 139872-500332. The pharmaceutical composition of any one of claims 28-31, wherein said RNAi agent is administered or suitable for administration in a buffer solution, optionally comprising acetate, citrate, prolamine, carbonate, or phosphate or any combination thereof.

33. A method of reducing or suppressing expression of an Transferrin receptor 2 (TFR2) gene in a cell compared to a pretreatment control or vehicle only control, the method comprising:(a) contacting the cell with the RNAi agent of any one of claims 1-26 or the pharmaceutical composition of any one of claims 28-32; and(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an TFR2 gene, thereby reducing or suppressing expression of the TFR2 gene in the cell;or(a) contacting a cell derived from a subject with the RNAi agent of any one of claims 1-26 or the pharmaceutical composition of any one of claims 28-32,(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an TFR2 gene, thereby reducing or suppressing expression of the TFR2 gene in the cell, and culturing the cell in vitro.

34. The method of claim 33, wherein said cell is within a subject.

35. The method of claim 34, wherein the subject is a human.

36. A method of treating a human subject having a disorder that would benefit from a reduction in TFR2 expression, comprising:administering to the subject the RNAi agent of any one of claims 1-26 or the pharmaceutical composition of any one of claims 28-32, thereby treating said subject; orcontacting a cell derived from the subject with the RNAi agent of any one of claims 1-26 or the pharmaceutical composition of any one of claims 28-32, optionally culturing the cell in vitro and administering the cell to the subject.

37. The method of any one of claims 33-36, wherein the subject suffers from a TFR2-associated disorder, optionally selected from anemia of inflammation, cancer-associated anemia, iron refractory iron deficiency anemia (IRIDA), p-thalassemia, autoimmune diseases (e.g., rheumatoid arthritis and lupus),DB1 / 167456146.4 380Attorney Docket No.: CTY-003PC / 139872-5003inflammatory bowel disease (e.g., Crohn’s Disease and ulcerative colitis), chronic kidney disease (CKD), and cancers with anemia of inflammation component, including solid cancers (e.g., lung cancer, ovarian cancer, colorectal cancer, breast cancer, prostate cancer, renal cancer, kidney cancer, gynecological cancers (e.g., uterine cancer, endometrial cancer, ovarian cancer, cervical cancer, vaginal cancer, and vulvar cancer), head and neck cancer, esophageal cancer, stomach cancer, gastric cancer, pancreatic cancer, liver cancer (e.g., hepatocellular carcinoma), and thyroid cancer), and blood cancers (e.g., acute leukemia, chronic leukemia, Hodgkin’s lymphoma, Non-Hodgkin, lymphoma, multiple myeloma, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms, myeloma (e.g., monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, and extramedullary plasmacytoma), and myelofibrosis.

38. The method of any one of claims 33-37, wherein the method reduces the expression of TFR2 in a liver tissue by at least about 30%, or at least about 40%, or at least about 50%, or at least about 60% compared to a pretreatment control or vehicle only control.

39. The method of any one of claims 33-38, wherein the method causes a reduction in TFR2 protein in the blood, plasma or serum by at least about 10%, or at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80% or more compared to a pretreatment control or vehicle only control.

40. The method of any one of claims 33-39, wherein the method causes an increase in the iron levels in the blood, plasma or serum by at least about 10%, or at least about 20%, or at least about 40%, or at least about 50%, or at least about 75%, or at least about 80%, or at least about 100%, or at least about 150% or more compared to the pre-treatment iron levels in the blood, plasma or serum.

41. The method of any one of claims 33-40, wherein the method causes an increase in transferrin saturation in the blood, plasma or serum by at least about 10%, or at least about 20%, or at least about 40%, or at least about 50%, or at least about 75%, or at least about 80%, or at least about 100%, or at least about 150% or more compared to the pre-treatment transferrin saturation in the blood, plasma or serum.

42. The method of any one of claims 33-41, wherein the method causes an increase in blood hemoglobin levels by at least about 10%, or at least about 20%, or at least about 40%, or at least about 50%, or at least about 75%, or at least about 80%, or at least about 100%, or at least about 150% or more compared to the pre-treatment blood hemoglobin levels.DB1 / 167456146.4 381Attorney Docket No.: CTY-003PC / 139872-500343. The method of any one of claims 33-42, wherein the RNAi agent is administered at a dosage in the range of about 0.3 mg / kg to about 10 mg / kg, or about 0.3 mg / kg to about 3 mg / kg, or about 1 mg / kg to about 10 mg / kg, or about 3 mg / kg to about 30 mg / kg, or about 0.01 mg / kg to about 0.1 mg / kg, or about 0.03 mg / kg to about 0.3 mg / kg, or about 0.1 mg / kg to about 1 mg / kg.

44. The method of any one of claims 33-43, wherein the RNAi agent is administered a frequency ranging from about once every 3 months to about once every 9 months, or about once every months to about once every 12 months, or about once every 2 months to about once every 10 months, or about once every 3 weeks to about once every 3 months, or about once every 4 weeks to about once every 4 months, or about once every 5 weeks to about once every 5 months, or about once every 6 weeks to about once every 6 months, or about once every 7 weeks to about once every 7 months, or about once every 8 weeks to about once every 8 months, or about once every 9 weeks to about once every 9 months.

45. The method of any one of claims 33-44, wherein the RNAi agent is administered to the subject intravenously or subcutaneously.

46. A kit for performing the method of any one of claims 33-45, the kit comprising a) the RNAi agent, and b) instructions for use, and c) optionally, a means for administering the RNAi agent to the subject.DB1 / 167456146.4 382

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