摘要:
The present invention provides conjugated double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and/or sugar modified nucleosides. More particularly, the present compositions comprise a linked conjugate group on one strand and a non hybridizing region of 2'-modified nucleosides on the other strand. Each strand further comprises one or more phosphorothioate internucleoside linkage. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
摘要:
The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.
摘要:
Methods are provided for the identification of compounds that selectively modulate epigenetic changes in gene expression. Compounds, compositions, kits or assays devices, and methods are provided for modulating the expression, endogenous levels or the function of small non-coding RNAs cognate to or transcribed by heterochromatic regions subject to epigenetic regulation (i.e., promoters, enhancers, centromeres, telomeres, origins of DNA replication, imprinted loci, or loci marked by dosage-compensation), and for modulating the formation or function of heterochromatin in cells, tissues or animals.
摘要:
The present invention provides double stranded compositions wherein one of the strands is useful in, for example, influencing the preferential loading the opposite strand into the RISC (or cleavage) complex. In particular, the present invention provides oligomeric compounds that comprise chemical modifications in at least one of the strands to drive loading of the opposite strand into the RISC (or cleavage) complex. Such modifications can be used to increase potency of duplex constructs that have been modified to enhance stability. Examples of chemical modifications that drive loading of the second strand include, but are not limited to, MOE (2'-O(CH 2 ) 2 OCH 3 ), 2'-O-methyl, -ethyl, -propyl, and -N-methylacetamide. Such modifications can be distributed throughout the strand, or placed at the 5' and/or 3' ends to make a gapmer motif on the sense strand. The activity of the 4'-thio gapmer RNA antisense strand can be improved by incorporating alternating MOE or MOE gapmer motif into the sense strand.
摘要:
Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.
摘要:
The present invention provides double stranded compositions wherein each strand is modified to have a motif defined by positioning of β-D-ribonucleosides and sugar modified nucleosides. More particularly, the present compositions comprise one strand having an alternating motif and another strand having a hemimer motif, a blockmer motif, a fully modified motif or a positionally modified motif. At least one of the strands has complementarity to a nucleic acid target. The compositions are useful for targeting selected nucleic acid molecules and modulating the expression of one or more genes. In preferred embodiments the compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. The present invention also provides methods for modulating gene expression.
摘要:
The present invention provides double stranded compositions wherein one of the strands is useful in, for example, influencing the preferential loading the opposite strand into the RISC (or cleavage) complex. In particular, the present invention provides oligomeric compounds that comprise chemical modifications in at least one of the strands to drive loading of the opposite strand into the RISC (or cleavage) complex. Such modifications can be used to increase potency of duplex constructs that have been modified to enhance stability. Examples of chemical modifications that drive loading of the second strand include, but are not limited to, MOE (2’-O(CH 2 ) 2 OCH 3 ), 2’-O-methyl, -ethyl, -propyl, and -N-methylacetamide. Such modifications can be distributed throughout the strand, or placed at the 5’ and/or 3’ ends to make a gapmer motif on the sense strand. The activity of the 4’-thio gapmer RNA antisense strand can be improved by incorporating alternating MOE or MOE gapmer motif into the sense strand.
摘要:
The present invention provides double stranded compositions wherein the first strand comprises three different regions and the second strand is native RNA. Each region has native or modified ribofuranosyl sugar moieties that are different than those of the other two regions. At least a portion of the first oligomeric compound is complementary to and hybridizes to a nucleic acid target. The present invention also provides methods for modulating gene expression using the modified oligomeric compounds and compositions of oligomeric compounds.
摘要:
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 a modification comprising a polycyclic sugar surrogate. 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 nucleoside of the oligomer has a polycyclic sugar surrogate modification.
摘要:
Methods for detecting and identifying unknown bioagents, including bacteria, viruses and the like, by a combination of microRNA containing nucleic acid amplification and molecular weight determination using primers which hybridize to conserved sequence regions of microRNA containing nucleic acids derived from a bioagent and which bracket variable sequence regions that uniquely identify the bioagent. The result is a "base composition signature" (BCS) or molecular mass which is then matched against a database of base composition signatures or molecular masses, by which the species of the bioagent is identified.