bc200614x_si_001.pdf (211.11 kB)
Download fileNew Sequence-Defined Polyaminoamides with Tailored Endosomolytic Properties for Plasmid DNA Delivery
journal contribution
posted on 2012-06-20, 00:00 authored by David Schaffert, Christina Troiber, Ernst WagnerHeterogeneity of polymeric carriers is one of the most
elusive
obstacles in the development of nonviral gene delivery systems, concealing
interaction mechanisms and limiting the use of structure–activity
relationship studies. In this report, novel sequence-defined polyaminoamides,
prepared by solid-phase assisted synthesis, were used to establish
first structure–activity relationships for polymer-based plasmid
DNA delivery. By combining a cationic building block with hydrophobic
modifications and bioreversible disulfide cross-linking sites, transfection
polymers with tailored lytic and DNA binding properties were designed.
These polymers demonstrated clear correlation between structure and
performance in lysis and DNA binding assays. In vitro studies showed
negligible toxicity and highly efficient gene transfer, demonstrating
the potential of this platform in the fast, combinatorial development
of new transfection polymers.