Methods and compositions for controlling efficacy of RNA silencing
AssigneeUniversity of Massachusetts
InventorsPhillip D. Zamore, Guiliang Tang
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Abstract
Based at least in part on an understanding of the mechanisms by which small RNAs (e.g., naturally-occurring miRNAs) mediate RNA silencing in plants, rules have been established for determining, for example, the degree of complementarity required between an RNAi-mediating agent and its target, i.e., whether mismatches are tolerated, the number of mismatches tolerated, the effect of the position of the mismatches, etc. Such rules are useful, in particular, in the design of improved RNAi-mediating agents which allow for more exact control of the efficacy of RNA silencing.
Claims35
A method of enhancing RNA silencing activity of an RNAi agent in a mammalian cell or a plant cell, comprising:
- (i) selecting a target sequence in an mRNA expressed in the mammalian or plant cell;
- and
- (ii) synthesizing an RNAi agent comprising an antisense strand that is complementary to the target sequence, wherein at least one nucleotide within 5 or fewer nucleotides from the 3′ end of the antisense strand is substituted with a nucleotide which forms a G:U wobble base pair when the antisense strand is base paired with the target sequence, such that the RNA silencing activity of the RNAi agent is enhanced.
Dependencies are inferred from the claim text.