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

First Author  Li J Year  2026
Journal  Front Immunol Volume  17
Mgi Jnum  J:393627 Mgi Id  MGI:8461514
Doi  10.3389/fimmu.2026.1941021 Citation  Li J, et al. (2026) An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells. Front Immunol 17
abstractText  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.
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