Inhibitor nucleic acids
First Claim
1. A double-stranded nucleic acid for inhibiting expression of a target gene by an RNA interference mechanism, comprising:
- a) a sense polynucleotide strand comprising one or more modifications or modified nucleotides;
b) an antisense polynucleotide strand, optionally comprising one or more modifications, having a designated sequence that hybridizes to at least a portion of a transcript of the target gene and is sufficient to inhibit expression of the target gene; and
c) an aptamer that binds to a preselected target.
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Accused Products
Abstract
The present invention provides methods and compositions for attenuating expression of a target gene in vivo. In general, the method includes administering RNAi constructs (such as small-interfering RNAs (i.e., siRNAs) that are targeted to particular mRNA sequences, or nucleic acid material that can produce siRNAs in a cell), in an amount sufficient to attenuate expression of a target gene by an RNA interference mechanism. In particular, the RNAi constructs may include one or more modifications to improve serum stability, cellular uptake and/or to avoid non-specific effect. In certain embodiments, the RNAi constructs contain an aptamer portion. The aptamer may bind to human serum albumin to improve serum half life. The aptamer may also bind to a cell surface protein that improves uptake of the construct.
139 Citations
27 Claims
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1. A double-stranded nucleic acid for inhibiting expression of a target gene by an RNA interference mechanism, comprising:
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a) a sense polynucleotide strand comprising one or more modifications or modified nucleotides;
b) an antisense polynucleotide strand, optionally comprising one or more modifications, having a designated sequence that hybridizes to at least a portion of a transcript of the target gene and is sufficient to inhibit expression of the target gene; and
c) an aptamer that binds to a preselected target. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A pharmaceutical preparation for delivery of an RNAi nucleic acid to an organism, the composition comprising a pharmaceutically acceptable carrier and a double-stranded nucleic acid, comprising:
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a) a sense polynucleotide strand comprising one or more modifications to the sugar-phosphate backbone; and
b) an RNA antisense polynucleotide strand having a designated sequence that hybridizes to at least a portion of a transcript of a target gene and is sufficient to inhibit expression of the target gene, wherein the one or more modifications to the sugar-phosphate backbone increase non-covalent association of the double-stranded nucleic acid with one or more species of protein as compared to an unmodified double-stranded nucleic acid having the designated sequence. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27)
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Specification