# Evolution, Optimization, and Application of Genome Editing Technologies

> **NIH NIH R35** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $773,490

## Abstract

Project Summary/Abstract
Gene editing technologies enable the efficient targeted introduction of desired genetic alterations of interest in
a wide range of organisms and have broad applications for biological research and human therapeutics. First-
generation gene editing platforms use site-specific endonucleases (e.g., RNA-guided CRISPR-Cas nucleases)
to induce targeted DNA double-stranded breaks, using cellular DNA repair mechanisms to create mutations.
More recently developed gene editing platforms include the CRISPR cytosine or adenine base editors, which
use Cas9-directed single-stranded DNA deaminases to induce targeted C-to-T or A-to-G alterations,
respectively, and CRISPR-guided prime editors (which use a reverse transcriptase-dependent process that
can induce any nucleotide substitution or small indel mutations). Although gene editing technology
development has accelerated over the past decade, many important limitations of existing platforms have yet
to be addressed and opportunities remain to create multiple new impactful technologies enabled by recent
advances. For the next cycle of this MIRA, the focus will be on four broadly important Challenges: 1) expand
the sensitivities and scope of gene editor off-target detection technologies; 2) engineer next-generation prime
editors with enhanced and optimized architectures; 3) create new epigenetic editing platforms for targeted
heritable activation of human genes; and 4) develop new universal modalities for delivery of all gene editors to
human cells.

## Key facts

- **NIH application ID:** 10330689
- **Project number:** 2R35GM118158-06
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** J. KEITH JOUNG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $773,490
- **Award type:** 2
- **Project period:** 2016-06-14 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330689

## Citation

> US National Institutes of Health, RePORTER application 10330689, Evolution, Optimization, and Application of Genome Editing Technologies (2R35GM118158-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10330689. Licensed CC0.

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