Tuning DNA Condensation with Zwitterionic Polyamidoamine (zPAMAM) Dendrimers

Cationic dendrimers are promising vectors for nonviral gene therapies due to their well-defined size and chemistry. We have synthesized a series of succinylated fourth generation (G4) PAMAM dendrimers to control the DNA packaging in dendriplexes, allowing us to probe the role of charge on DNA packaging. The self-assembly of DNA induced by these zwitterionic PAMAM (zPAMAM) was investigated using small-angle X-ray scattering (SAXS). We demonstrate that changing the degree of modification in zPAMAM–DNA significantly alters the packing density of the resulting dendriplexes. Salt sensitivities and pH dependence on the inter-DNA spacing were also examined. The swelling and stability to salt are reduced with increasing degree of PAMAM modification. Lowering the pH leads to significantly tighter hexagonal DNA packaging. In combination, these results show zPAMAM is an effective means to modulate nucleic acid packaging in a deterministic manner.