| 摘要 |
RNAi constructs directed to MAP4K4 that demonstrate unexpectedly high gene silencing activities, and uses thereof are disclosed. The blunt-ended constructs have a double-stranded region of 19-49 nucleotides. The constructs have selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the strands may be modified (e.g., one or both ends of the sense strand is modified by 2′-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, the antisense strand may also be modified by a 2′-O-methyl group at the penultimate 5′-end nucleotide to greatly reduce off-target silencing. |
| 主权项 |
1. A double-stranded RNA (dsRNA) for inhibiting expression of a MAP4K4 gene, comprising an antisense strand sequence that has complementarity to a target sequence on an mRNA of the MAP4K4 gene and a sense strand sequence that comprises at least 12 contiguous nucleotides of SEQ ID NO: 1, 3, 5, 7, 11, 12, 13, 15, 17, 19, 21, 25, 27, 31, 33, 35, 37, 45, or 50. |
