MODIFIED ANTISENSE OLIGOMERS FOR EXON INCLUSION IN SPINAL MUSCULAR ATROPHY

1 - 24 . (canceled)

25 . A compound of formula (VII):

or a pharmaceutically acceptable salt thereof, wherein:

each Nu is a nucleobase which taken together form a targeting sequence;

Z is an integer from 6 to 38;

T is a moiety of the formula:

each R 1 is independently selected from:

R 2 is selected from H, acyl, trityl, 4-methoxytrityl, and C 1 -C 6 alkyl,

wherein at least one R 1 is:

and wherein the targeting sequence: (a) comprises a sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13, (b) is selected from SEQ ID NOS: 4, 6-8, 11, and 13, or (c) is a fragment of at least 8 contiguous nucleotides of a targeting sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13.

26 . The compound of claim 25 , wherein at least one R 1 is

27 . The compound of claim 25 , wherein T is:

28 . The compound of claim 25 , wherein R 2 is H.

29 . The compound of claim 25 , wherein at least one R 1 is

and T is:

30 . The compound of claim 25 , wherein T is:

and R 2 is H.

31 . The compound of claim 25 , wherein each R 1 is independently selected from

T is:

R 2 is H, wherein at least one R 1 is

32 . The compound of claim 25 , wherein the compound is a compound of formula (VIIa):

or a pharmaceutically acceptable salt thereof, where:

each Nu is a nucleobase which taken together form a targeting sequence;

Z is an integer from 6 to 38; and

each R 1 is independently selected from:

wherein at least one R 1 is:

33 . The compound of claim 25 , wherein Z is an integer from 16 to 23.

34 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 4.

35 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 6.

36 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 7.

37 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 8.

38 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 11.

39 . The compound of claim 25 , wherein the targeting sequence is SEQ ID NO: 13.

40 . The compound of claim 25 , wherein the compound is PMO-1, PMO-2, PMO-3, PMO-4, PMO-7, PMO-9, PMO-APN-2, PMO-APN-11, PMO-APN-16, PMO-APN-17, PMO-APN-29, PMO-APN-31, PMO-Plus-2, PMO-Plus-8, PMO-Plus-9, PMO-Plus-11, PMO-Plus-13, PMO-R 6 Gly-2, or PMO-R 6 Gly-3.

41 . A pharmaceutical composition comprising a compound of formula (VII):

or a pharmaceutically acceptable salt thereof, wherein:

each Nu is a nucleobase which taken together form a targeting sequence;

Z is an integer from 6 to 38;

T is a moiety of the formula:

each R 1 is independently selected from:

R 2 is selected from H, acyl, trityl, 4-methoxytrityl, and C 1 -C 6 alkyl,

wherein at least one R 1 is:

and wherein the targeting sequence: (a) comprises a sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13, (b) is selected from SEQ ID NOS: 4, 6-8, 11, and 13, or (c) is a fragment of at least 8 contiguous nucleotides of a targeting sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13.

42 . A method of treating spinal muscular atrophy (SMA) in a subject in need thereof, comprising administering to the subject an effective amount of a compound of formula (VII):

or a pharmaceutically acceptable salt thereof, wherein:

each Nu is a nucleobase which taken together form a targeting sequence;

Z is an integer from 6 to 38;

T is a moiety of the formula:

each R 1 is independently selected from:

R 2 is selected from H, acyl, trityl, 4-methoxytrityl, and C 1 -C 6 alkyl,

wherein at least one R 1 is:

and wherein the targeting sequence: (a) comprises a sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13, (b) is selected from SEQ ID NOS: 4, 6-8, 11, and 13, or (c) is a fragment of at least 8 contiguous nucleotides of a targeting sequence selected from SEQ ID NOS: 4, 6-8, 11, and 13.