Antisense oligonucleotides with increased RNase sensitivity
First Claim
1. An antisense oligonucleotide having improved RNase activation characteristics comprising an RNase activation region and a plurality of adjacent universal bases, wherein said antisense oligonucleotide recruits and/or activates an RNase when hybridized to a target polynucleotide, wherein each said universal base comprises an unnatural nucleobase analog, and wherein said plurality of adjacent universal bases increase the activity of said RNase to cleave a target molecule compared to an antisense oligonucleotide without said plurality of adjacent universal bases.
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Abstract
Combinatorial libraries comprise first oligonucleotide analogs and second oligonucleotide analogs which are coupled together to form antisense molecules capable of binding target polynucleotides and activating an RNase, and ribozymes capable of cleaving polynucleotides.
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Citations
50 Claims
- 1. An antisense oligonucleotide having improved RNase activation characteristics comprising an RNase activation region and a plurality of adjacent universal bases, wherein said antisense oligonucleotide recruits and/or activates an RNase when hybridized to a target polynucleotide, wherein each said universal base comprises an unnatural nucleobase analog, and wherein said plurality of adjacent universal bases increase the activity of said RNase to cleave a target molecule compared to an antisense oligonucleotide without said plurality of adjacent universal bases.
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45. An antisense oligonucleotide comprising an RNase activation region and a plurality of adjacent universal bases, wherein each said universal base comprises an unnatural nucleobase analog;
- wherein said oligonucleotide acts as a substrate for an RNase when hybridized to a target nucleic acid, wherein said RNase recognizes double stranded RNA or RNA/DNA hybrids; and
wherein said plurality of adjacent universal bases increase the activity of said RNase to cleave a target molecule compared to an antisense oligonucleotide without said plurality of adjacent universal bases. - View Dependent Claims (46, 47, 48)
- wherein said oligonucleotide acts as a substrate for an RNase when hybridized to a target nucleic acid, wherein said RNase recognizes double stranded RNA or RNA/DNA hybrids; and
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49. An antisense oligonucleotide comprising a plurality of adjacent universal bases, wherein said antisense oligonucleotide recruits an RNase when hybridized to a target polynucleotide;
- wherein each said universal base comprises an unnatural nucleobase analog, and wherein said plurality of adjacent universal bases increase the activity of said RNase to cleave a target molecule compared to an antisense oligonucleotide without said plurality of adjacent universal bases.
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50. An antisense oligonucleotide comprising a binding domain and a plurality of adjacent universal bases, wherein said antisense oligonucleotide recruits an RNase when hybridized to a target polynucleotide;
- wherein each said universal base comprises an unnatural nucleobase analog, and wherein said plurality of adjacent universal bases increase the activity of said RNase to cleave a target molecule compared to an antisense oligonucleotide without said plurality of adjacent universal bases.
Specification