CPC C12N 15/113 (2013.01) [C12N 2310/141 (2013.01)] | 11 Claims |
1. A programmable, conditionally activatable small interfering RNA (Cond-siRNA) construct comprising a sensor strand, a core strand, and a guide strand, wherein:
(i) the sensor strand and the core strand form a sensor duplex,
(ii) the guide strand and the core strand form a RNAi duplex, and
(iii) the sensor duplex is attached to the RNAi duplex to form a single structure, wherein the terminal base on the 5′ terminus of the core strand is a 2′-F or 2′-O-methyl and the terminal base on the 3′ terminus of the core strand is a 2′-F or 2′-O-methyl, and wherein
(a) 50% or less of the backbone positions in the sensor duplex domain of the sensor strand are phosphorothioate (PS) connections, or
(b) the three bases of the core strand base-paired with the 3′ terminus of the guide strand have a M*+*M pattern, wherein M is a 2′-F or 2′-O-methyl, * is a PS backbone connection, and + is an LNA base or other 2′-4′ bridged base.
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