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Peer-reviewedCC BY 4.0Frontiers in Immunology

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

  • Jian Li1
  • Beatriz Goncalves1,2
  • Gabrielle Melamed1
  • Dillon O’Neill1,3
  • Ryan Cozzone1
  • Sara Iuliucci1
  • Austin Cozzone1
  • Mohamad-Gabriel Alameh1,3,4,5
  • Leyuan Ma1,3,4,6,7
7 affiliations
  1. 1The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia
  2. 2Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania
  3. 3Department of Experimental Pathology, Children’s Hospital of Philadelphia
  4. 4Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania
  5. 5Institute of RNA Innovation, University of Pennsylvania
  6. 6Center for Cellular Immunotherapies, University of Pennsylvania
  7. 7Abramson Cancer Center, University of Pennsylvania
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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.

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Cite

BibTeXRIS
BibTeX
@article{li2026inducible,
  title = {{An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells}},
  author = {Jian Li and Beatriz Goncalves and Gabrielle Melamed and Dillon O’Neill and Ryan Cozzone and Sara Iuliucci and Austin Cozzone and Mohamad-Gabriel Alameh and Leyuan Ma},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1941021},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941021/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells
AU  - Jian Li
AU  - Beatriz Goncalves
AU  - Gabrielle Melamed
AU  - Dillon O’Neill
AU  - Ryan Cozzone
AU  - Sara Iuliucci
AU  - Austin Cozzone
AU  - Mohamad-Gabriel Alameh
AU  - Leyuan Ma
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1941021
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1941021/full
AB  - 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.
SN  - 1664-3224
ER  -