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AssigneeMassachusetts Institute of Technology
InventorsDarrell J. Irvine, Ron Weiss, Yingzhong Li, Jan Lonzaric, Parisa Yousefpour
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Genetic circuits have been developed to regulate behaviors of replicon RNA in responses to small molecules, which has broader applications, such as for quantitative expression of cargo genes, temporary expression of immunomodulatory cytokines or antigens for better cancer immunotherapy or vaccination, and for increased safety in use of self-replicating vectors or in combination with other viral-delivery vectors. Described herein are genetic circuits suitable for systems that either require a tight off state or a slow off state, which can serve for instance where either a kill switch or prolonged protein expression (e.g., of vaccine antigens) are needed.
A genetic circuit for regulating responses of replicon RNA to small molecules, comprising one or more RNA replicons replicated by an RNA-dependent RNA polymerase (RdRp), wherein the one or more RNA replicons comprises one or more output sequences and a sequence encoding a nonstructural protein (nsP) 3 (nsP3) modified by fusion to a first destabilization domain (DD) which is stabilized in the presence of a first small molecule,
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