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Engineering multiple levels of specificity in an RNA viral vector

Gao, Xiaojing J. and Chong, Lucy S. and Ince, Michaela H. and Kim, Matthew S. and Elowitz, Michael B. (2020) Engineering multiple levels of specificity in an RNA viral vector. . (Unpublished)

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Synthetic molecular circuits could provide powerful therapeutic capabilities, but delivering them to specific cell types and controlling them remains challenging. An ideal "smart" viral delivery system would enable controlled release of viral vectors from "sender" cells, conditional entry into target cells based on cell-surface proteins, conditional replication specifically in target cells based on their intracellular protein content, and an evolutionarily robust system that allows viral elimination with drugs. Here, combining diverse technologies and components, including pseudotyping, engineered bridge proteins, degrons, and proteases, we demonstrate each of these control modes in a model system based on the rabies virus. This work shows how viral and protein engineering can enable delivery systems with multiple levels of control to maximize therapeutic specificity.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper ItemFlow cytometry data analysis software
Gao, Xiaojing J.0000-0002-3094-1456
Chong, Lucy S.0000-0002-5858-9984
Ince, Michaela H.0000-0002-8997-3188
Kim, Matthew S.0000-0002-5836-8874
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Posted May 27, 2020. We thank J. Ruan and A. Erskine for technical assistance; R. Zhu, Z. Singer, H. McBride, and L. Luo for critical feedback. The research was funded by DARPA (HR0011-17-2-0008, M.B.E.), the Gordon and Betty Moore Foundation (GMBF2809, M.B.E.), NIH (T32 GM07616, L.S.C., 1K99EB027723-01, X.J.G.), National Science Foundation Graduate Research Fellowship Program (DGE-1745301 ,L.S.C) and the Helen Hay Whitney Foundation (F1047, X.J.G.). M.B.E is a Howard Hughes Medical Institute investigator. Author contributions: X.J.G. and L.S.C. conceived of the project. X.J.G., L.S.C., M.S.K., and M.B.E. designed experiments. X.J.G., L.S.C., M.H.I. and M.S.K. performed experiments. X.J.G., L.S.C. and M.B.E. analyzed data. X.J.G., L.S.C., and M.B.E. wrote the manuscript, with input from all authors. Competing interests: X.J.G, L.S.C., M.S.K., and M.B.E. are inventors on a U.S. patent provisional application related to this work. Data and materials availability: All DNA constructs will be available from Addgene, and cell lines are available from M.B.E. under a material transfer agreement with Caltech. The datasets generated and analyzed and the computer code used during the current study are available at, DOI 10.22002/D1.1438 . Flow cytometry data analysis software used for this study is available at
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0008
Gordon and Betty Moore FoundationGMBF2809
NIH Predoctoral FellowshipT32 GM07616
NSF Graduate Research FellowshipDGE-1745301
Helen Hay Whitney FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20200529-070622811
Persistent URL:
Official Citation:Engineering multiple levels of specificity in an RNA viral vector. Xiaojing J Gao, Lucy S Chong, Michaela H Ince, Matthew S Kim, Michael B Elowitz. bioRxiv 2020.05.27.119909; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103534
Deposited By: Tony Diaz
Deposited On:29 May 2020 15:44
Last Modified:29 May 2020 15:44

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