Precise PBAEs: A Highly Efficient Single‐Molecularly Defined Gene‐Delivery System

Gene-delivery polymers have wide therapeutic applications. The structures (e.g., molecular weight, polymer sequence, end groups, and topology) of gene-delivery polymers are of crucial importance to their properties including transfection efficiency, toxicity, and targeting capability. Thus, precise control over the structures of gene-delivery polymers is extremely beneficial for property optimizations and manufacturing reproducibility. However, sequence-defined gene-delivery polymers with high efficiency and low toxicity are rare, limited by synthetic strategies. In this work, we developed a method that enables poly(β-amino esters), one of the most promising gene-delivery polymers, to be synthesized with precisely controlled and vastly variable molecular weight, end group, and topology. This synthetic strategy creates a new family of gene-delivery polymers with defined structures, offering significant potentials and revealing new design principles.