bioRxiv : the preprint server for biologyOct 10, 2026

Engineering human immune cells to carry gene editing tools

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 11, 2026

Abstract

Primary human T cells can produce functional Cas9 ribonucleoproteins in retroviral-based enveloped delivery vehicles.

T cells are capable of delivering gene editing tools to various target cells.
The engineered T cells utilize a miniaturized system that is more effective than existing delivery methods.
Cas9-EDVs can edit a broad range of target cells when combined with fusogenic VSV-G.
This approach may enhance the potential for gene editing applications by overcoming current delivery limitations.

Simplified

Clinical applications of gene editors including CRISPR-Cas9 are limited by the cell-type specificity and tissue penetrance of current in vivo delivery options. Cell-mediated gene editor delivery could overcome these obstacles. To date, systems utilizing immortalized cell lines have demonstrated gene editor delivery in vitro . Because T cells traffic throughout the organism and engage in intercellular communication with individual target cells, we wondered whether they could be engineered to deliver gene editing machinery. Here, we demonstrate that primary human T cells can produce retroviral-based enveloped delivery vehicles (EDVs) packaging functional Cas9 ribonucleoproteins. When paired with fusogenic VSV-G, T cell-generated Cas9-EDVs edited a diverse array of target cells. We developed a miniaturized Moloney murine leukemia virus-based system that proved superior to existing architectures in this context and optimized both lentiviral and site-specific knock-in approaches for T cell engineering. These Enveloped Particle Information Courier-(EPIC-) T cells offer key advantages as delivery systems.

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Engineering human immune cells to carry gene editing tools

Abstract

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