Chimeric oligomeric compounds and their use in gene modulation

Abstract

Oligomer compositions comprising first and second oligomers are provided wherein at least a portion of the first oligomer is capable of hybridizing with at least a portion of the second oligomer, at least a portion of the first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and at least one of the first or second oligomers includes at least one nucleotide comprising a chimeric organic composition. Oligomer/protein compositions are also provided comprising an oligomer complementary to and capable of hybridizing to a selected target nucleic acid and at least one protein comprising at least a portion of an RNA-induced silencing complex (RISC), wherein at least one nucleotide comprising a chimeric organic composition.

1 - 118 . (canceled) 
     
     
         119 . A composition comprising a first oligomer and a second oligomer, wherein:
 at least a portion of said first oligomer is capable of hybridizing with at least a portion of said second oligomer,   at least a portion of said first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and   at least one of said first or said second oligomers is a chimeric oligomeric compound,
 wherein the chimeric oligomeric compound is a gapmer. 
   
     
     
         120 . The composition of  claim 119  wherein said gapmer comprises two terminal segments having nucleotides of a first type and an internal segment having nucleotides of a second type and where said nucleotides of said first type are different from said nucleotides of said second type. 
     
     
         121 . The composition of  claim 120  wherein said nucleotides of said first type each comprise a 2′ sugar substituent. 
     
     
         122 . The composition of  claim 119  wherein each of said first and second oligomers has 15 to 30 nucleotides. 
     
     
         123 . The composition of  claim 119  wherein said first oligomer is the at least one chimeric oligomeric compound. 
     
     
         124 . The composition of  claim 119  wherein at least one of said first or said second oligomers comprises a conjugate group. 
     
     
         125 . The composition of  claim 119  wherein said chimeric oligomeric compound comprises at least one phosphorothioate internucleoside linkage. 
     
     
         126 . The composition of  claim 125  wherein said chimeric oligomeric compound comprises at least two phosphorothioate internucleoside linkages. 
     
     
         127 . The composition of  claim 126  wherein the at least two phosphorothioate internucleoside linkages are the terminal internucleoside linkages of said chimeric oligomeric compound. 
     
     
         128 . The composition of  claim 125  wherein each of the internucleoside linkages of said chimeric oligomeric compound are independently selected from phosphorothioate and phosphodiester. 
     
     
         129 . A composition comprising a first oligomer and a second oligomer, wherein:
 at least a portion of said first oligomer is capable of hybridizing with at least a portion of said second oligomer,   at least a portion of first oligomer is complementary to and capable of hybridizing to a selected target nucleic acid, and   at least one of said first or said second oligomers is a chimeric oligomeric compound,
 wherein the chimeric oligomeric compound is a blockmer. 
   
     
     
         130 . The composition of  claim 129  wherein said blockmer comprises an oligonucleotide having a block of at least two consecutive nucleotides of a first type located immediately adjacent at least one nucleotide of a second type and
 wherein said nucleotides of said first type are different from said nucleotides of said second type. 
 
     
     
         131 . The composition of  claim 130  wherein said nucleotides of said first type comprise a 2′ sugar substituent. 
     
     
         132 . The composition of  claim 131  wherein each of said 2′ sugar substituents are independently selected from 2′-OCH 3 , 2′-F, and 2′-MOE. 
     
     
         133 . The composition of  claim 129  wherein the 5′ terminal nucleotide of said chimeric oligomeric compound comprises a modified or unmodified 5′-phosphate group. 
     
     
         134 . The composition of  claim 129  wherein at least one terminal internucleoside linkage of said chimeric oligomeric compound is a modified internucleoside linkage. 
     
     
         135 . The composition of  claim 134  wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         136 . The composition of  claim 134  wherein the modified internucleoside linkage is a 2′-5′ internucleoside linkage. 
     
     
         137 . The composition of  claim 129  wherein said first oligomer is said chimeric oligomeric compound. 
     
     
         138 . The composition of  claim 129  wherein each of said first and said second oligomers is a chimeric oligomeric compound, wherein each of said chimeric oligomeric compounds is a blockmer.