Multiple oligonucleotide moieties on peptide carrier

Abstract

The present disclosure relates to antisense oligonucleotides (AONs), such as phosphorodiamidate morpholino oligonucleotides (PMOs). The present disclosure further relates to the conjugation of multiple PMOs to cationic cell penetrating peptides (CPPs) to enhance the uptake of PMOs into skeletal and cardiac muscle cells.

What is claimed is: 
     
         1 . A peptide conjugated AON compound comprising at least two AON compounds comprising from 15 to 30 subunits of Formulas (I), (II), (III), (IV), (V), or (VI):
 wherein B is a naturally occurring purine or pyrimidine nucleotide base selected from C, G, A, or T;   wherein said at least two AON compounds have a nucleotide base sequence that is complementary to at least 75% of the bases of a target pre-mRNA or mRNA,   wherein said at least two AON compounds have from 0 to 3 repeating subunits where B is G;   wherein said at least two AON compounds have less than 60% of said subunits where B is C or G;   wherein said at least two AON compounds have a non-self-complimentary sequence; and   wherein said at least two AON compounds are conjugated to a polycationic peptide.   
     
     
         2 . A peptide conjugated phosphorodiamidate morpholino compound comprising at least two phosphorodiamidate morpholino compounds comprising from 15 to 30 subunits of Formula (I): 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group and B is a naturally occurring purine or pyrimidine nucleotide base selected from C, G, A, or T; 
         wherein said at least two phosphorodiamidate morpholino compounds have a nucleotide base sequence that is complementary to at least 8 contiguous bases of a target pre-mRNA or mRNA; 
         wherein said at least two phosphorodiamidate morpholino compounds have from 0 to 3 repeating subunits where B is G; 
         wherein said at least two phosphorodiamidate morpholino compounds have less than 60% of said subunits where B is C or G; 
         wherein said at least two phosphorodiamidate morpholino compounds have a non-self-complimentary sequence; and 
         wherein said at least two phosphorodiamidate morpholino compounds are conjugated to a polycationic peptide.