Antisense oligonucleotides that target a cryptic splice site in ush1c as a therapeutic for usher syndrome

Abstract

The present invention provides a method for treating Usher's syndrome in a human subject including administering to the human subject an oligonucleotide having 8 to 30 linked nucleosides having a nucleobase sequence comprising a complementary region comprising at least 8 contiguous nucleobases complementary to a target region of equal length within exon 3 of an Usher RNA transcript.

1 .- 7 . (canceled) 
     
     
         8 . A method for treating Usher's syndrome type 1C in a human subject comprising:
 administering to the human subject suffering from Usher's syndrome type 1C an oligonucleotide comprising 8 to 30 linked nucleosides comprising a nucleobase sequence of SEQ ID NO: 5, SEQ ID NO: 17, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 53, or SEQ ID NO: 59.   
     
     
         9 . The method of  claim 8 , wherein the nucleobase sequence is SEQ ID NO: 32. 
     
     
         10 . The method of  claim 8 , wherein the nucleobase sequence is SEQ ID NO: 33. 
     
     
         11 . The method of  claim 8 , wherein the oligonucleotide is chemically modified to be different from a naturally occurring oligonucleotide with the same sequence. 
     
     
         12 . The method of  claim 11 , wherein the naturally occurring oligonucleotide with the same sequence comprises a sugar moiety, a base moiety, and a phosphodiester linking group and the chemically modified oligonucleotide has a different sugar moiety, a different base moiety, a different linking group, or combinations of any of these modifications. 
     
     
         13 . The method of  claim 12 , wherein the chemical modification is to the sugar moiety. 
     
     
         14 . The method of  claim 13 , wherein the sugar moiety in the naturally occurring oligonucleotide is a ribose sugar and the different sugar moiety is a morpholine ring. 
     
     
         15 . The method of  claim 13 , wherein the sugar moiety in the naturally occurring oligonucleotide is a ribose sugar and the different sugar moiety is a furanosyl. 
     
     
         16 . The method of  claim 15 , wherein the furanosyl has chemical substituents to form bicyclic or tricyclic sugars. 
     
     
         17 . The method of  claim 8 , wherein the step of administering an oligonucleotide redirects splicing from a cryptic splice site to a major splice site. 
     
     
         18 . The method of  claim 8 , wherein the step of administering an oligonucleotide comprises delivering the oligonucleotide to the subject by a parenteral, oral, injection, transdermal, intramuscular, or topical route of administration. 
     
     
         19 . The method of  claim 8 , wherein the step of administering an oligonucleotide comprises injecting the oligonucleotide directly into an eye of the subject, an ear of the subject, or both the eye and ear of the subject.