Programming primary human T cells to deliver gene editing machinery
- 1University of California, San Francisco
Abstract
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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BibTeX
@misc{meixiong2026programming,
title = {{Programming primary human T cells to deliver gene editing machinery}},
author = {J. Meixiong and O. Zginnyk and L. Chow and B. R. Shy and M. H. Spitzer},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.753584},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.753584v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Programming primary human T cells to deliver gene editing machinery
AU - J. Meixiong
AU - O. Zginnyk
AU - L. Chow
AU - B. R. Shy
AU - M. H. Spitzer
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.753584
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.753584v1
AB - 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.
ER -