US 11,999,954 B2
Programmable conditional SIRNAS and uses thereof
Si-ping Han, Duarte, CA (US); William A. Goddard, III, Pasadena, CA (US); Marwa Ben Haj Salah, Duarte, CA (US); Lisa Scherer, Duarte, CA (US); and John J. Rossi, Duarte, CA (US)
Assigned to Clty of Hope, Duarte, CA (US); and California Institute of Technology, Pasadena, CA (US)
Filed by CITY OF HOPE, Duarte, CA (US); and CALIFORNIA INSTITUTE OF TECHNOLOGY, Pasadena, CA (US)
Filed on Feb. 10, 2021, as Appl. No. 17/172,461.
Application 17/172,461 is a continuation of application No. PCT/US2019/046075, filed on Aug. 10, 2019.
Claims priority of provisional application 62/811,183, filed on Feb. 27, 2019.
Claims priority of provisional application 62/717,686, filed on Aug. 10, 2018.
Prior Publication US 2021/0230593 A1, Jul. 29, 2021
Int. Cl. C12N 15/113 (2010.01)
CPC C12N 15/113 (2013.01) [C12N 2310/141 (2013.01)] 11 Claims
OG exemplary drawing
 
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.