An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells.

Authors

Jian Li, Beatriz Goncalves, Gabrielle Melamed, Dillon O'Neill, Ryan Cozzone, Sara Iuliucci, Austin Cozzone, Mohamad-Gabriel Alameh, Leyuan Ma

Published in

Frontiers in immunology. Volume 17. Pages 1941021. Epub Oct 07, 2026.

Abstract

Lentivirus (LV)-based manipulation of immune cells is a commonly used approach in cell therapies. However, the most frequently used Vesicular Stomatitis Virus Glycoprotein (VSV-G) pseudotyping approach is inefficient to support LV gene delivery of mouse immune cells due to the lack of an optimal entry receptor. Here, we present a transgenic mouse model with Cre recombinase-inducible expression of the human Low Density Lipoprotein Receptor (hLDLR), the natural entry receptor of VSV-G LV. Surprisingly, we found that Cre induces robust hLDLR expression across multiple immune cells only under activation conditions. Induction of hLDLR expression by genetic crossing with Cre-transgenic mice or exposure to Cre mRNA-lipid nanoparticles (LNPs) potently sensitized murine immune cells, especially T cells, to VSV-G LV-mediated gene delivery. This novel transgenic mouse model serves as a valuable tool for investigating immune cell function and engineered cell therapies for cancer in syngeneic mouse models.

PMID:
42909043
Bibliographic data and abstract were imported from PubMed on 23 Oct 2026.

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