An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells
Year: 2026
Type: article
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.
Source: Frontiers in Immunology
Authors: Jian Li, Beatriz Goncalves, Gabrielle Melamed, Dillon O’Neill, Ryan Cozzone, Sara Iuliucci, Austin Cozzone, Mohamad-Gabriel Alameh, Leyuan Ma
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: Melanoma Research Alliance, University of Pennsylvania, Institute for Translational Medicine and Therapeutics, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
OpenAlex ID: W7220832523