REDUCED SIZE SELF-DELIVERING RNAI COMPOUNDS
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Accused Products
Abstract
The present invention relates to RNAi constructs with minimal double-stranded regions, and their use in gene silencing. RNAi constructs associated with the invention include a double stranded region of 8-14 nucleotides and a variety of chemical modifications, and are highly effective in gene silencing.
46 Citations
127 Claims
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1-91. -91. (canceled)
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92. An isolated double stranded nucleic acid molecule comprising a guide strand and a passenger strand,
wherein the region of the molecule that is double stranded is from 8-15 nucleotides long, wherein the guide strand contains a single stranded region that is 4-12 nucleotides long, wherein the single stranded region of the guide strand contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 phosphorothioate modifications, and wherein at least 40% of the nucleotides of the double stranded nucleic acid are modified.
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94. (canceled)
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97. (canceled)
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100-103. -103. (canceled)
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104. An isolated asymmetric nucleic acid molecule comprising:
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a first polynucleotide wherein the first polynucleotide is complementary to a second polynucleotide and a target gene; and a second polynucleotide, wherein the second polynucleotide is at least 6 nucleotides shorter than the first polynucleotide, wherein the first polynucleotide includes a single stranded region of 6, 7, 8, 9, 10, 11 or 12 nucleotides, wherein the single stranded region of the first polynucleotide contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 phosphorothioate modifications, wherein the asymmetric nucleic acid molecule also includes a double stranded region, and wherein at least 50% of C and U nucleotides in the double stranded region are 2′
O-methyl modified or 2′
-fluoro modified. - View Dependent Claims (105, 107)
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106. (canceled)
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108. An isolated double stranded nucleic acid molecule comprising:
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a guide strand of 17-21 nucleotides in length that has complementarity to a target gene, and a passenger strand of 8-16 nucleotides in length, wherein the guide strand and the passenger strand form the double stranded nucleic acid molecule having a double stranded region and a single stranded region, wherein the guide strand has a 3′
single stranded region of 4-12 nucleotides in length, wherein the single stranded region comprises 2-12 phosphorothioate modifications, wherein at least 40% of the nucleotides of the double stranded nucleic acid are modified, and wherein at least one modification is a hydrophobic base modification and/or the double stranded nucleic acid molecule is linked to a hydrophobic conjugate. - View Dependent Claims (109, 111, 113)
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110. (canceled)
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112. (canceled)
- 114. An isolated single stranded RISC entering polynucleotide, wherein at least 30% of the nucleotides within the polynucleotide are modified and wherein at least two of the modifications are hydrophobic base modifications.
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116. (canceled)
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118. (canceled)
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119. A method for inhibiting the expression of a target gene in a mammalian cell, comprising contacting the mammalian cell with an isolated double stranded nucleic acid molecule comprising a guide strand and a passenger strand,
wherein the region of the molecule that is double stranded is from 8-15 nucleotides long, wherein the guide strand contains a single stranded region that is 4-12 nucleotides long, wherein the single stranded region of the guide strand contains 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 phosphorothioate modifications, and wherein at least 40% of the nucleotides of the double stranded nucleic acid are modified.
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121. (canceled)
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124. (canceled)
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127-130. -130. (canceled)
Specification