期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 141, 期 21, 页码 8416-8421出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b03154
关键词
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资金
- NSF [CHE-1607092, CHE848280]
- NIH [CA031845]
- Child Health Research Institute at Stanford University
- Stanford SPARK Translational Research Program
- Abbott Laboratories Stanford Graduate Fellowship
- National Institute of Biomedical Imaging and Bioengineering of the NIH [F32EB021161]
- NIH S10 Shared Instrument Grant [S10RR027431-01]
RNA technology is transforming life science research and medicine, but many applications are limited by the accessibility, cost, efficacy, and tolerability of delivery systems. Here we report the first members of a new class of dynamic RNA delivery vectors, oligo(serine ester)-based charge-altering releasable transporters (Ser-CARTs). Composed of lipid-containing oligocarbonates and cationic oligo(serine esters), Ser-CARTs are readily prepared (one flask) by a mild ring opening polymerization using thiourea anions and, upon simple mixing with mRNA, readily form complexes that degrade to neutral serine-based products, efficiently releasing their mRNA cargo. mRNA/Ser-CART transfection efficiencies of >95% are achieved in vitro. Intramuscular or intravenous (iv) injections of mRNA/Ser-CARTs into living mice result in in vivo expression of a luciferase reporter protein, with spleen localization observed after iv injection.
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