Cell reports methodsDec 4, 2025

Improving CRISPR-Cas9 Gene Editing Using HDAC Inhibitors and Designed Virus-Like Particles

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

FAME-CRISPR increased CRISPR-Cas9 editing efficiency by combining pan-HDAC inhibition with engineered virus-like particle delivery.

Evidence

This platform experiment tested pan-HDAC inhibitor treatment with eVLP transduction for DSB-mediated CRISPR and base editing in immortalized cancer cells and primary diploid fibroblasts, reporting 4-fold higher efficiency and edited populations within 2- to 3-cell mean population doublings.

Caveat

The evidence is limited to cell-model editing performance and does not establish in vivo delivery, safety, or therapeutic efficacy.

Simplified

CRISPR-mediated gene editing using engineered virus-like particles (eVLPs) can achieve high efficiency, but performance varies with reduced effectiveness often seen in primary cells or when generating polyclonal models at scale. We developed a faster, accurate and 4-fold more efficient CRISPR-Cas9 (FAME-CRISPR) method using pan-histone deacetylase inhibitors with eVLP transduction compared to previous reports using other histone deacetylase inhibitors. Combined optimization of pan-HDACi treatment with eVLP enhanced double-strand break (DSB)-mediated CRISPR and base editing gave significantly edited populations within 2- to 3-cell mean population doublings, reducing the need for post-editing selection in immortalized cancer cells and in primary diploid fibroblasts that have limited replicative lifespans.