{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:50:31Z","timestamp":1791355831164,"version":"4.3.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["DP2 AI164319-03"],"award-info":[{"award-number":["DP2 AI164319-03"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1941021","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:59:55Z","timestamp":1791352795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An inducible human LDLR transgenic mouse model for enhanced lentiviral gene delivery to murine immune cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Jian","family":"Li","sequence":"first","affiliation":[{"name":"The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Goncalves","sequence":"additional","affiliation":[{"name":"The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]},{"name":"Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Melamed","sequence":"additional","affiliation":[{"name":"The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"The Raymond G. 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