Extended dicer substrate agents and methods for the specific inhibition of gene expression
US8513207B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | Dec 18, 2009 |
| Grant date | Aug 20, 2013 |
| Priority date | — |
| Expiry date | May 26, 2030 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2320/52
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a pattern of deoxyribonucleotides (in most embodiments, the pattern comprises at least one deoxyribonucleotide-deoxyribonucleotide base pair) designed to direct the site of Dicer enzyme cleavage within the dsNA molecule. Deoxyribonucleotides of the dsNA molecules of the invention are located within a region of the dsNA that can be excised via Dicer cleavage to generate an active siRNA agent that no longer contains the deoxyribonucleotide pattern (e.g., deoxyribonucleotide-deoxyribonucleotide base pairs). Such DNA-extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be more effective RNA inhibitory agents than corresponding double stranded RNA-extended DsiRNAs. DsiRNA agents were also found to tolerate guide strand mismatches.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.