Modified RNAi polynucleotides and uses thereof
US10131904B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Feb 11, 2009 |
| Grant date | Nov 20, 2018 |
| Priority date | — |
| Expiry date | Feb 11, 2029 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N2320/53
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2′-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2′-O-methyl group at the 2nd 5′-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.