OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF
Among other things, the present disclosure relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer. In some embodiments, a chirally controlled oligonucleotide composition has any sequence of bases, and/or pattern or base modifications, sugar modifications, backbone modifications and/or stereochemistry, or combination of these elements, described herein.
1 - 41 . (canceled)
42 . A method for treating Huntington's disease in a subject, comprising administering to the subject a therapeutically effective amount of an oligonucleotide having the structure of:
mG * SmGmCmAmC * SA * SA * SG * SG * SG * SC * SA * SC * RA * SG * SmAmCmUmU * SmC (SEQ ID NO: 360), or a pharmaceutically acceptable salt thereof, wherein:
S represents a Sp phosphorothioate;
R represents a Rp phosphorothioate; and
m represents a 2′-OMe modification to a nucleoside.
43 . The method of claim 42 , wherein the oligonucleotide is in a salt form.
44 . The method of claim 42 , wherein the oligonucleotide is a sodium salt.
45 . The method of claim 42 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.
46 . The method of claim 43 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.
47 . The method of claim 44 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.
48 . A method for treating Huntington's disease in a subject, comprising administering to the subject a pharmaceutical composition which comprises a therapeutically effective amount of an oligonucleotide and at least one pharmaceutically acceptable inactive ingredient selected from pharmaceutically acceptable diluents, pharmaceutically acceptable excipients, and pharmaceutically acceptable carriers, wherein the oligonucleotide has the structure of:
mG * SmGmCmAmC * SA * SA * SG * SG * SG * SC * SA * SC * RA * SG* SmAmCmUmU * SmC (SEQ ID NO: 360), or a pharmaceutically acceptable salt thereof, wherein:
* S represents a Sp phosphorothioate;
*R represents a Rp phosphorothioate; and
m represents a 2′-OMe modification to a nucleoside.
49 . The method of claim 48 , wherein the oligonucleotide is in a salt form.
50 . The method of claim 48 , wherein the oligonucleotide is a sodium salt.
51 . The method of claim 48 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.
52 . The method of claim 49 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.
53 . The method of claim 50 , wherein the subject has an rs362307 allele which is associated with Huntington's disease and is 100% complementary to the base sequence of the oligonucleotide.