Rna interference suppression of neurodegenerative diseases and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2016281084-A1
Application number	US-201514931667-A
Country	US
Kind code	A1
Filing date	Nov 3, 2015
Priority date	Aug 5, 2002
Publication date	Sep 29, 2016
Grant date	—

Abstract

The present invention is directed to small interfering RNA molecules (siRNA) targeted against nucleic acid sequence that encodes huntingtin or ataxin-1, and methods of using these siRNA molecules.

First claim

1 . An isolated RNA duplex comprising a first strand of RNA and a second strand of RNA, wherein the first strand comprises at least 15 contiguous nucleotides encoded by shSCA1.F10 (SEQ ID NO:102), shSCA1.F11 (SEQ ID NO:103), SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:63, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72, SEQ ID NO:74, SEQ ID NO:76, SEQ ID NO:78, SEQ ID NO:80, SEQ ID NO:82, SEQ ID NO:84, SEQ ID NO:86, or SEQ ID NO:88, SEQ ID NO:90, SEQ ID NO:96 through SEQ ID NO:101 or SEQ ID NO:106 through SEQ ID NO:142, and wherein the second strand is complementary to at least 12 contiguous nucleotides of the first strand.

2 . The RNA duplex of claim 1 , wherein the duplex is between 15 and 30 base pairs in length.

3 . The RNA duplex of claim 1 , wherein the duplex is between 19 and 25 base pairs in length.

4 . The RNA duplex of claim 1 , wherein the first and/or second strand further comprises an overhang region.

5 . The RNA duplex of claim 1 , wherein the first and/or second strand further comprises a 3′ overhang region, a 5′ overhang region, or both 3′ and 5′ overhang regions.

6 . The RNA duplex of claim 4 , wherein the overhang region is from 1 to 10 nucleotides in length.

7 . The RNA duplex of claim 1 , wherein the first strand and the second strand are operably linked by means of an RNA loop strand to form a hairpin structure comprising a duplex structure and a loop structure.

8 . The RNA duplex of claim 7 , wherein the loop structure contains from 4 to 10 nucleotides.

9 . The RNA duplex of claim 7 , wherein the loop structure contains 4, 5 or 6 nucleotides.

10 . The RNA duplex of claim 7 , wherein the loop structure corresponds to SEQ ID NO:61 or SEQ ID NO:64.

11 . An expression cassette comprising a nucleic acid encoding at least one strand of the RNA duplex of claim 1 .

12 . The expression cassette of claim 11 , further comprising a promoter.

13 . The expression cassette of claim 12 , wherein the promoter is a regulatable promoter.

14 . The expression cassette of claim 12 , wherein the promoter is a constitutive promoter.

15 . The expression cassette of claim 12 , wherein the promoter is a CMV, RSV, pol II or pol III promoter.

16 . The expression cassette of claim 11 , wherein the expression cassette further comprises a polyadenylation signal.

17 . The expression cassette of claim 16 , wherein the polyadenylation signal is a synthetic minimal polyadenylation signal.

18 . The expression cassette of claim 11 , further comprising a marker gene.

19 . A vector comprising the expression cassette of claim 11 .

20 - 25 . (canceled)

26 . A method of suppressing the accumulation of huntingtin or ataxin-1 in a cell comprising introducing a ribonucleic acid (RNA) of claim 1 into the cell in an amount sufficient to suppress accumulation of huntingtin or ataxin-1 in the cell.

27 - 61 . (canceled)

Assignees

• Univ Iowa Res Found

Inventors

• Davidson Beverly L
• Xia Haibin
• Mao Qinwen
• Paulson Henry
• Boudreau Ryan
• Harper Scott

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N2310/111

  spanning the whole gene, or a large part of it · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C12N2799/021

  for the expression of a heterologous nucleic acid · CPC title

• C12N2799/025

  where the vector is derived from a parvovirus · CPC title