Adaptation of transgene mRNA translation boosts the anticancer efficacy of oncolytic HSV1.

ABSTRACT:

Background

Transgenes deliver therapeutic payloads to improve oncolytic virus immunotherapy. Transgenes encoded within oncolytic viruses are designed to be highly transcribed, but protein synthesis is often negatively affected by viral infection, compromising the amount of therapeutic protein expressed. Studying the oncolytic herpes simplex virus-1 (HSV1), we found standard transgene mRNAs to be suboptimally translated in infected cells.

Methods

Using RNA-Seq reads, we determined the transcription start sites and 5'leaders of HSV1 genes and uncovered the US11 5'leader to confer superior activity in translation reporter assays. We then incorporated this 5'leader into GM-CSF expression cassette in oncolytic HSV1 and compared the translationally adapted oncolytic virus with the

SUBMITTER: Hoang HD 

PROVIDER: S-EPMC10040010 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature