Engineering multiple levels of specificity in an RNA viral vector

Abstract

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.

(Un)Easily Possible Synthetic Biology

“…Most of the challenges synthetic biologists have been tackling in recent research relate to the increasing complexity of the synthetic systems, as the research has moved from bacteria to different cell types and multicellular organisms and addressed the stochastic nature of cellular processes. When it comes to making use of synthetic biology in multicellular organisms, one of the challenges results from transporting synthetic circuits into cells (Gao et al 2020). Here, special attention needs to be paid to preventing the circuits from becoming integrated into the host genome.…”