Chen Lab

Broad Institute, Inc.

Cambridge · United States

NIH-funded
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NIH R01 · 2025

Multiplexed Locus-Specific Hypermutation for Functional Characterization of the Coding and Noncoding Genome

SUMMARY While laboratory directed evolution has become a workhorse for generating novel therapeutics and synthetic biomolecules, few tools exist for directly evolving the endogenous mammalian genome. Most tools have extremely broad or narrow targeting windows (e.g., alkylators that introduce mutations genome-wide2 or CRISPR base-editors that target narrow windows of 4-10 nts3,4). To systematically evolve entire gene regulatory networks and query gene functions with base-level resolution, we must develop targeted long-range approaches that can quickly introduce variants in gene sets and in multiple regulatory elements that contribute to gene expressions. Here, we will develop a novel…

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