Many functional platforms have been rationally designed with the hope of mimicking the complicated DNA histone machinery. The design of highly performant DNA vectors for efficient cellular uptake represents a grand challenge. However, DNA and target cells are highly variable and rational design is limited to a relatively small number of components. One possible solution to this problem is to employ the dynamic screening approaches. Herein, adaptive Dynamic Constitutional Frameworks, based on hydrophobic tails, polyethylene glycol and cationic heads components, which are reversibly connected to core centers are combined and tested as DyNAvectors for DNA transfection. Depending on their tunable composition, these modular nanovectors dynamically self-adapt to their DNA targets, allowing the rapid screening of most effective vectors, optimally matched to DNA 3D surrounding space. Our strategy avoids complicate synthetic steps and allows easy and efficient identification of adaptive vectors with high DNA complexation ability, good transfection efficiency, and well tolerated by mammalian cells.

DyNAvectors: Dynamic constitutional vectors for adaptive DNA delivery

256th National Meeting (2018)

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