Dynameric Frameworks for DNA Transfection

The design of performant nonviral vectors for efficient cellular DNA uptake represents a grand challenge. The variability of DNA targets and of the transfected cells limits the discovery of highly active nonviral vectors. Dynamic constitutional strategy presented here, combining easy synthesis and rapid screening, enables the selection of dynameric frameworks, DFs, for DNA transfection. On the basis of reversible recombination of cationic heads and of hydrophilic/hydrophobic network-constitutive building blocks, the multivalent core–shell dendritic architectures with an optimal diameter of 100 nm may be adaptively generated in the presence of DNA targets. The fittest DFs simultaneously exhibit optimal DNA binding, superior transfection yield to standard transfection SuperFect agent and preserve high HEK 293T cell viability. The present results constitutes an important advancement toward novel biologically friendly, low-cost, and efficient nonviral vectors.