期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 45, 页码 20083-20089出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202008082
关键词
combinatorial chemistry; drug delivery; gene therapy; imidazole-containing lipids; T cell engineering
资金
- National Institutes of Health (NIH) [R01 EB027170-01, UG3 TR002636-01]
- NIH Research Infrastructure Grant [NIH S10 OD021624]
Engineering T lymphocytes is an emerging approach in a variety of biomedical applications. However, delivering large biologics to primary T lymphocytes directly in vivo is technically challenging due to the low transfection efficacy. Herein, we investigated a library of synthetic lipid-like molecules (lipidoids) for their capability of delivering mRNA into primary T lymphocytes both ex vivo and in vivo. We initially screened a library with a large structural variety of lipidoids ex vivo and identified imidazole-containing lipidoids that are particularly potent in T lymphocytes transfection. We further optimized lipidoid structures by constructing and screening a detailed lipidoid library containing imidazole or imidazole analogues to perform a structure-activity correlation analysis. Using the lead lipidoid as a delivery vehicle for Cre mRNA in vivo through intravenous injection, we achieved 8.2 % gene recombination in mouse T lymphocytes.
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