Gene therapy is a technology with great potential, but only two gene therapy agents have been FDA approved thus far. The barriers for gene-based therapeutics to reach the clinic are multi-faceted, including safety of vectors in vitro and in animal studies, gene transfer optimization, long-term persistence of viral vectors in the host, and sustained transgene expression in vivo. Cell-based gene therapy, though a viable and emerging alternative to viral vectors, relies on autologous cell therapy, which has a number of challenges associated with it.

Nanoengineering is an attractive option for safe and effective gene delivery to target organs. Though no nanoengineering techniques have yet reached the clinic, many have shown promise in preclinical trials. Polymer-based approaches using PEI/liposomes as gene delivery vehicles are a few of the approaches that have been investigated in preclinical trials so far. The success of effective gene delivery is reliant on biological insights into the engineering of these nanoparticle-based delivery vehicles to delineate key factors, such as physiological and cellular barriers, nucleic acid cargo stability, immunogenicity, and ease of delivery in an in vivo model system.

This Methods Collection will focus on current approaches in nanoengineering for the delivery of genetic cargo and highlight the challenges that nanoengineering can overcome compared to traditional viral-based gene delivery techniques.