Overcoming Barriers to Achieve Safe, Sustained and Efficient Non-Viral Gene Therapy

Invited Review:Adverse events in using viral-based vectors to deliver and integrate therapeutic DNA into patients in recent clinical trials have revitalized efforts to improve the efficacy of the alternative, the much safer non-viral vectors. Non-viral vectors are generally orders of magnitude less efficient than viral counterparts due their inability to overcome numerous biological barriers to DNA delivery, but deeper understanding of these barriers, and formulation of new approaches to transcend them, has enabled the generation of non-viral vectors for DNA delivery that comprise multiple functional modules mimicking the ability of viruses to traffic through the cell to the nucleus. These novel, multifunctional vectors may be combined with strategies for episomal replication and faithful expression of therapeutic DNA bereft of the potential dangers of integration into the host genome, with enormous potential for future clinical as well as research applications