| Autor: |
Benner NL; Department of Chemistry , Stanford University , Stanford , California 94305 , United States., McClellan RL; Department of Chemistry , Stanford University , Stanford , California 94305 , United States., Turlington CR; Department of Chemistry , Stanford University , Stanford , California 94305 , United States., Haabeth OAW; Department of Medicine, Division of Oncology, Stanford Cancer Institute , Stanford University , Stanford , California 94305 , United States., Waymouth RM; Department of Chemistry , Stanford University , Stanford , California 94305 , United States., Wender PA; Department of Chemistry , Stanford University , Stanford , California 94305 , United States.; Department of Chemical and Systems Biology , Stanford University , Stanford , California 94305 , United States. |
| Abstrakt: |
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. |
