Project Grant R01GM165764

The National Institute of General Medical Sciences awarded the University of Massachusetts Medical School $2,001,691 on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop PURGE, a computational toolkit for prioritizing guide RNAs in CRISPR epigenome editing applications.

The research addresses a fundamental limitation in CRISPR-based epigenome editing: only 10–20 percent of guide RNAs targeting distal regulatory elements successfully modulate gene expression, despite the identification of over two million putative regulatory elements across the genome. PURGE will distinguish itself from existing tools by deriving scoring metrics directly from catalytically inactive Cas9–DNA binding data rather than from nuclease-active Cas9 cutting data, better reflecting the mechanics of epigenome editing. The first aim will derive on-target Cas9 binding and activity scores for CRISPRi using high-density DNA-binding arrays. The second aim will derive off-target binding and activity scores through orthogonal in vitro and cell-based CRISPRi experiments. The third aim will validate on-target and off-target PURGE scores for CRISPRa.

Work is performed in Worcester, Massachusetts. The period of performance runs from September 1, 2026, through August 31, 2030. The award is a Project Grant, the standard assistance type for investigator-initiated research under NIGMS.