3D Macrocyclic Structure Boosted Gene Delivery: Multi-Cyclic Poly(β-Amino Ester)s from Step Growth Polymerization

The topological structuresof polymers play a critical role indetermining their gene delivery efficiency. Exploring novel polymericstructures as gene delivery vectors is thus of great interest. Inthis work, a new generation of multi-cyclic poly(& beta;-amino ester)s(CPAEs) with unique topology structure was synthesized for the firsttime via step growth polymerization. Through controlling the occurrencestage of cyclization, three types of CPAEs with rings of differentsizes and topologies were obtained. In vitro experiments demonstratedthat the CPAEs with macro rings (MCPAEs) significantly boosted thetransgene expression comparing to their branched counterparts. Moreover,the MCPAE vector with optimized terminal group efficiently deliveredthe CRISPR plasmid coding both Staphylococcus aureus Cas9 nuclease and dual guide sgRNAs for gene editing therapy.