Single-stranded RNAi agents containing an internal, non-nucleic acid spacer
AssigneeSirna Therapeutics, Inc.
InventorsLee Lim, Guillaume Chorn, Aarron T. Willingham, Lihong Zhao
Life of this patent
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Abstract
Single-stranded RNA molecules comprise one or more internal, non-nucleotide spacers, covalently linked with nucleotide portions of the molecule are provided. The single-stranded RNA molecules function as guide or antisense strands that are capable of inhibiting gene expression via an RNA interference mechanism, and thus represent single-stranded RNAi agents. The single-stranded RNAi molecules can be used in methods for a variety of therapeutic, diagnostic, target validation, genomic discovery, genetic engineering, and pharmacogenomic applications.
Claims26
A single-stranded RNA molecule that mediates RNA interference against a target RNA, wherein said single-stranded RNA molecule comprises:
- (a) a nucleic acid portion comprising a first nucleotide portion (N1) and a second nucleotide portion (N2) that are not self complementary, wherein said nucleic acid portion comprises at least 8 nucleotides that can base pair with a target site of the target RNA, and wherein the total number of nucleotides within the nucleic acid portion is from 8 to 26 nucleotides;
- (b) an internal spacer portion, wherein said spacer portion comprises at least a first non-nucleotide spacer portion (S1) that covalently links the first and second nucleotide portions wherein said single-stranded RNA molecule comprises the following structure:
- 5′N1-S1-N2 3′
- wherein:
- (i) N1 contains either one nucleotide or a contiguous stretch of nucleotides;
- (ii) S1 contains one or more non-nucleotide spacers covalently linking N1 and N2;
- (iii) N2 contains either one nucleotide or a contiguous stretch of nucleotides;
- (iv) S1 is at the 3′ end of N1 and at the 5′ end of N2;
- and
- (v) wherein said single-stranded RNA molecule has one 3′ end;
- and
- (c) a ligand.
Dependencies are inferred from the claim text.