# Improving Lytic Potency of Herpes Virus Cancer Therapeutics

> **NIH NIH R21** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $165,300

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite the recent FDA approval of the oncolytic herpes simplex virus, ImlygicTM to treat melanoma, and the
promising antitumor efficacy observed in many preclinical models using other similar viruses, strategies are still
need to improve the anti-cancer effectiveness of herpes virotherapy. Our preliminarily results using a so-called
“directed evolution” strategy in a low-permissive cell culture support our overarching hypothesis that more
effective virus mutants can be created via serial selection of mixed virus infections in poorly
permissive cells. Combining sequencing analysis and CRISPR/Cas9 gene editing approaches, we developed
our lead strain Mut-3∆34.5, which is attenuated with RL1/γ134.5 deletion. We found this novel virus induces a
giant syncytia phenotype and contains five nonsynonymous alternations, including the A151T in Us8/gE, that
potentially underlie the increased cancer cell killing effect of Mut-3∆34.5. The aims of this project are: (1)
Determine the mechanism(s) underlying the increased potency of Mut-3∆34.5 virus in oncolysis, (2) Delineate
the role of the non-parental non-synonymous mutations in Mut-3∆34.5 and (3) Define the safety profile and
efficacy of attenuated Mut-3∆34.5 virus in animal models. Our overarching goal is to further develop more
potent yet safe viral vectors for future clinical use.

## Key facts

- **NIH application ID:** 9850942
- **Project number:** 5R21CA223104-02
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** TIMOTHY P CRIPE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $165,300
- **Award type:** 5
- **Project period:** 2019-01-16 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850942

## Citation

> US National Institutes of Health, RePORTER application 9850942, Improving Lytic Potency of Herpes Virus Cancer Therapeutics (5R21CA223104-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850942. Licensed CC0.

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