# A novel human T-cell platform to define biological effects of genome editing

> **NIH NIH U01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $610,710

## Abstract

PROJECT SUMMARY
Genome editing technologies have extraordinary potential as new genomic medicines that address underlying
genetic causes of human disease; however, it remains challenging to predict their long-term safety, because we
do not know the consequences of potential side effects of genome editing such as off-target mutations or
immunogenicity. Our long-term goal is to understand and predict such unintended biological effects to advance
the development of safe and effective therapies. T-cells are an ideal cellular model because: 1) they are highly
relevant as the most widely used cells for development of therapeutic genome editing strategies (such as cell-based treatments for HIV and cancer) and 2) mature T-cells encode a diverse T-cell receptor repertoire that can
be exploited as built-in cellular barcodes for quantifying clonal expansion or depletion in response to specific
treatments. We, therefore, propose the following specific aims: 1) to predict which unintended editing sites have
biological effects on human T-cells by integrating large-scale genome-wide activity and epigenomic profiles with
state-of-the-art deep learning models and 2) to develop a human primary T-cell platform to detect functional
effects of genome editing by measuring clonal representation, off-target mutation frequencies, immunogenicity,
or gene expression. If successful, our experimental and predictive framework will profoundly increase confidence
in the safety of the next generation of promising genome editing therapies.

## Key facts

- **NIH application ID:** 10016298
- **Project number:** 8U01AI157189-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Shengdar Tsai
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $610,710
- **Award type:** 8
- **Project period:** 2018-09-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016298

## Citation

> US National Institutes of Health, RePORTER application 10016298, A novel human T-cell platform to define biological effects of genome editing (8U01AI157189-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10016298. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*