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Polymeric vectors for gene delivery are a promising alternative for clinical applications, as they are generally safer than viral counterparts. Our objective was to further our mechanistic understanding of polymer structure-function relationships to allow the rational design of new biomaterials. Utilizing poly(β-amino ester)s (PBAEs), we investigated polymer-DNA binding by systematically varying the polymer molecular weight, adding single carbons to the backbone and side chain of the monomers that constitute the polymers, and varying the type of polymer end group. We then sought to correlate how PBAE binding affects the polyplex diameter and ζ potential, the transfection efficacy, and its associated cytotoxicity in human breast and brain cancer cells in vitro. Among other trends, we observed in both cell lines that the PBAE-DNA binding constant is biphasic with the transfection efficacy and that the optimal values of the binding constant with respect to the transfection efficacy are in the range (1-6) × 10(4) M(-1). A binding constant in this range is necessary but not sufficient for effective transfection.

The Effect and Role of Carbon Atoms in Poly(β-amino ester)s for DNA Binding and Gene Delivery