# Non-viral genome, epigenome, and transcriptome engineering for clinical CAR-T cell manufacturing

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $263,928

## Abstract

PROJECT SUMMARY / ABSTRACT
The goal of this application is to train Dr. Brian Shy, a physician scientist at the University of California San
Francisco, with the skills necessary to become an independently-funded investigator studying, developing, and
manufacturing engineered cellular therapies. This research proposal will evaluate CRISPR-based non-viral
methods for targeted genome, epigenome, and transcriptome engineering in primary human T cells. This will be
applied to understand DNA repair pathway choice and DNA toxicity responses in order to improve site-specific
“knock-in” strategies with large therapeutic constructs such as chimeric antigen receptors (CARs), develop safe
and efficient methods for multiplexed T cell modifications, and establish Good Manufacturing Practice (GMP)
compatible processes for clinical implementation of this diverse toolset. This research is accompanied by a
career development and training plan that will build on Dr. Shy's clinical training in Transfusion Medicine and
Cellular Therapy, and his prior expertise in the pre-clinical development and manufacturing of experimental
cellular therapies. Training will focus on 1) implementation of novel cellular engineering tools, 2) next generation
sequencing (NGS) technologies and analysis of large datasets, 3) GMP manufacturing and pre-clinical
development, 4) clinical trial design and standard-of-care cellular therapies, and 5) laboratory management,
grant writing, presentation, and research strategy skills. This career development and training plan will include a
combination of formal coursework, mentored practical training; conference, meeting, and workshop attendance;
and guidance from an exceptional team of co-mentors, advisors, and collaborators. Altogether, this award will
help prepare Dr. Shy for an independent research career focused on developing improved cellular therapies for
treatment of cancer and other human diseases.

## Key facts

- **NIH application ID:** 10909062
- **Project number:** 5K08CA273529-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Brian R Shy
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $263,928
- **Award type:** 5
- **Project period:** 2022-09-02 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909062

## Citation

> US National Institutes of Health, RePORTER application 10909062, Non-viral genome, epigenome, and transcriptome engineering for clinical CAR-T cell manufacturing (5K08CA273529-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909062. Licensed CC0.

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