Massachusetts Institute of Technology

The Ohio State University

Yingzhong Li

Darrell J Irvine

Ron Weiss

Karl Dane Wittrup

Yizhou Dong

Noor Momin

Jan Lonzaric

Parisa Yousefpour

The present disclosure relates to synthetic oncolytic viruses comprising a lipid nanoparticle comprising one or more types of lipid and a self-amplifying replicon RNA comprising a sequence that encodes an immunomodulatory molecule.

Synthetic oncolytic LNP-replicon RNA and uses for cancer immunotherapy

The disclosure provides methods for an in vitro evolution technique to identify and characterize mutations in the non-structural genes of an alphavirus replicon that increase the strength and persistence of expression of the replicon genome. Also provided herein are in vivo methods for administering to an animal model a mutated alphavirus replicon that codes for a gene of experimental or therapeutic interest in the subgenome of the alphavirus replicon. The mutations identified herein improve the therapeutic potential of self-replicating RNA, which may have implications for cancer immunotherapy and beyond, e.g., for vaccination or gene therapy.

Methods for in vitro evolution of constructs derived from viruses

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.

Control of replication and transcription of self-replicating RNA in response to small molecules

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Quincy, MA, United States of America

Yingzhong Li