Cell genomicsJul 14, 2026

Using engineered virus-like particles together improves precise gene editing and large-scale testing

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 15, 2026

Abstract

PRIME-VLP achieves 1.5- to 2.9-fold improvements in prime editing efficiency across diverse genomic targets and cell types.

Engineered virus-like particles enable transgene-free delivery of genetic material for genome editing.
Prime editing, while precise, typically has limited efficiency that can be improved.
PRIME-VLP utilizes multiple rounds of delivery to enhance editing outcomes without increasing off-target effects.
The method maintains cellular health and does not disrupt normal gene activity.
A library of 6,000 pegRNAs targeting TP53 resulted in 2.8-fold higher editing efficiency compared to traditional methods.
This approach helps identify genetic variants associated with resistance to certain therapies.

Simplified

Engineered virus-like particles (eVLPs) enable transgene-free ribonucleoprotein delivery for genome editing, yet optimized strategies for high-throughput applications remain unexplored. Prime editing enables precise genomic modifications but suffers from limited efficiency. Here, we present PRIME-VLP (Progressive Repeated Infections for Maximized Editing via Virus-Like Particles), which exploits eVLP-mediated editing kinetics through multiple sequential sub-saturating transductions at optimal intervals. PRIME-VLP achieves 1.5- to 2.9-fold improvements in prime editing efficiency across diverse genomic targets and cell types without increasing off-target editing, compromising cellular viability or causing transcriptional perturbations. By decoupling pegRNA and editor delivery through pegRNA-free eVLPs, PRIME-VLP enables pooled prime editing screens and circumvents transgene silencing limitations. Using a 6,000-pegRNA library targeting TP53, PRIME-VLP achieved 2.8-fold higher editing and improved reproducibility compared to conventional lentiviral delivery, identifying TP53 loss-of-function variants conferring Nutlin-3 resistance. This work expands the versatility of eVLPs beyond their current in vivo therapeutic applications, demonstrating their promise for high-throughput functional genomics.