Oncolytic viruses derived from the gamma34.5-deleted herpes simplex virus recombinant R3616 encode a truncated UL3 protein.

Publication/Presentation Date

5-1-2006

Abstract

Replication-competent herpes simplex virus (HSV-1) mutants are used in clinical trials in the experimental treatment of cancer. Mutants G207, HSV1716, NV1020, and Oncovex GM-CSF share in common a defect in one or both copies of the gene encoding the neurovirulence factor, ICP34.5, and are thus neuroattenuated. These viruses are acknowledged to differ from one another (a) in the specific types of mutations intentionally introduced during their derivation and (b) in the inherent genetic differences retained from the different parent strains used in their construction. Unintended mutations are expected to emerge at some low frequency during the selection for and passage of mutant viruses. Here we demonstrate that during the construction of the oncolytic virus R3616, a nonsense mutation arose in an untargeted region of the HSV-1 genome that resulted in a substantial truncation of the viral protein known as UL3. This report is the first published documentation that oncolytic herpesviruses developed and used in clinical trials contain adventitious mutations. The implications of these findings for the characterization and development of vectors proposed for use in clinical trials are discussed.

Volume

13

Issue

5

First Page

891

Last Page

898

ISSN

1525-0016

Disciplines

Medicine and Health Sciences

PubMedID

16574492

Department(s)

Fellows and Residents

Document Type

Article

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