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

> **NIH NIH U01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $610,061

## 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:** 10202452
- **Project number:** 5U01AI157189-04
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Shengdar Tsai
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $610,061
- **Award type:** 5
- **Project period:** 2018-09-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202452

## Citation

> US National Institutes of Health, RePORTER application 10202452, A novel human T-cell platform to define biological effects of genome editing (5U01AI157189-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10202452. Licensed CC0.

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