Gene medicines: The end of the beginning?

Abstract

First-generation gene medicines and genetic vaccines represent a promising new class of therapeutics that have the potential to prevent, correct, or modulate genetic or acquired diseases. The rational design of synthetic gene delivery and expression systems continues to be essential to enable the precise temporal and spatial control of transgene expression in vivo. With the tantalizing efficacy results and outstanding safety profile observed with nonviral, plasmid-based product candidates in early clinical trials, a multidisciplinary approach remains critical to further improve the effectiveness, reduce the manufacturing costs, and maintain the safety of gene therapeutics and vaccines for their successful development. This commentary provides an historical perspective on somatic gene therapy and briefly addresses the rate-limiting steps in effective gene transfer and expression. The importance of understanding plasmid pharmacokinetics after administration by conventional routes in animal models and in humans is emphasized. Pharmaceutical scientists have a pivotal role to play in deciphering the key biological parameters to effective gene transfer and designing gene delivery systems that will enable plasmid-based products to become an integral part of the future medical armamentarium.