# Enzymatic modification of nucleobases for single base pair editing in genomic DNA

> **NIH NIH F32** · BROAD INSTITUTE, INC. · 2021 · $66,390

## Abstract

PROJECT SUMMARY/ABSTRACT
 Targeted rewriting of the genetic code of developed cells for therapeutic benefit is a longstanding goal in the
biomedical sciences. Base editing is a new genome engineering approach that harnesses the sequence-
specific targeting ability of a catalytically inactive or impaired Cas9 nuclease to target nucleobase-tailoring
enzymes to specific locations in the genome, eventually causing targeted single base mutations. In the ternary
complex between Cas9, sgRNA, and the target DNA, a portion of the non-templated strand of DNA forms an
exposed, disordered, single-stranded loop. In base editing, an enzyme fused to Cas9 takes advantage of this
opportunity and catalyzes chemical modifications on nucleobases within a small segment of this loop. These
modifications are designed to alter the base pairing properties of the modified nucleotide, and miscoding during
DNA replication or repair effects the eventual point mutation. The long term goal of this project is to discover
productive base pairing interactions of modified nucleobases and to harness these modifications in developing
base editors capable of selectively effecting every permutation of a point mutation. A protein engineering
approach to optimize new nucleobase-oxidizing enzymes will be undertaken, and a combination of chemical
synthesis and enzymology will allow for the evaluation of the miscoding potential of modified nucleobases.
Base editors are anticipated to have a direct impact on human health: the majority of pathogenic human
genetic mutations are point mutations, and base editing has the potential to reverse these mutations in somatic
cells.

## Key facts

- **NIH application ID:** 10174965
- **Project number:** 5F32GM133088-03
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Jaron Mercer
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174965

## Citation

> US National Institutes of Health, RePORTER application 10174965, Enzymatic modification of nucleobases for single base pair editing in genomic DNA (5F32GM133088-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10174965. Licensed CC0.

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