Open AccessFunctional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs)
Author(s) -
Nancy L. Benner,
Katherine E. Near,
Michael Bachmann,
Christopher H. Contag,
Robert M. Waymouth,
Paul A. Wender
Publication year - 2018
Publication title -
biomacromolecules
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.689
H-Index - 220
eISSN - 1526-4602
pISSN - 1525-7797
DOI - 10.1021/acs.biomac.8b00401
Subject(s) - transfection , liposome , gene delivery , lipofectamine , dna , chemistry , biophysics , monomer , amphiphile , cationic polymerization , cart , biochemistry , recombinant dna , polymer , biology , organic chemistry , vector (molecular biology) , gene , mechanical engineering , engineering , copolymer
Safe and effective DNA delivery systems are required to enable or enhance clinical strategies and research involving gene therapy and DNA vaccinations. To address this delivery problem, a series of charge-altering releasable transporters (CARTs) with varied lipid content were prepared and evaluated for plasmid DNA (pDNA) delivery into cultured cells. These lipid-modified CART co-oligomers were synthesized in only two steps via sequential organocatalytic ring-opening polymerization of lipid-containing cyclic carbonate monomers and morpholinone monomers. Lipid variations of the CARTs substantially impacted the delivery efficiency of pDNA, with oleyl- and linoleyl-based CARTs showing enhanced performance relative to the commercial transfection agent Lipofectamine 2000 (L2000). The best-performing oleyl CART was carried forward to study stable luciferase transfection with a Sleeping Beauty ( SB) transposon system. The oleyl CART outperformed the L2000 positive control with respect to stable transfection efficiency. CART-pDNA complexes represent a new DNA delivery system for research and clinical applications.