Synthetic virology approaches to improve the safety and efficacy of oncolytic virus therapies.

ABSTRACT: The large coding potential of vaccinia virus (VV) vectors is a defining feature. However, limited regulatory switches are available to control viral replication as well as timing and dosing of transgene expression in order to facilitate safe and efficacious payload delivery. Herein, we adapt drug-controlled gene switches to enable control of virally encoded transgene expression, including systems controlled by the FDA-approved rapamycin and doxycycline. Using ribosome profiling to characterize viral promoter strength, we rationally design fusions of the operator element of different drug-inducible systems with VV promoters to produce synthetic promoters yielding robust inducible expression with undetectable baseline levels. We also generate chimeric synthetic promoters facilitating additio

SUBMITTER: Azad T 

PROVIDER: S-EPMC10213590 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature