First Insights into Non-invasive Administration Routes for Non-viral Gene Therapy

Gene delivery has attracted increasing interest as a highly promising therapeutic method to treat various diseases, including both genetic and acquired disorders. However, its clinical application is still hampered by the lack of safe and effective gene delivery techniques, as well as by the need of non-invasive routes of administration in gene delivery platforms. Among the different approaches used to transport nucleic acids into target cells, non-viral vectors represent promising and safer alternatives to viruses. Non-invasive administration routes are currently being studied, such as intranasal administration to target the brain, topical retinal administration for ocular diseases and aerosolized formulations for inhalation for the treatment of pulmonary diseases. Reasonable evidence suggests that future gene delivery systems might be based on effective non-viral vectors administered through non-invasive routes, which would constitute a safe, easy to produce, cheap and customizable alternative to the current viral gene delivery platforms. In this review, after briefly introducing the basis of gene therapy, we discuss the up-to-date and possible future strategies to improve DNA transfection efficiency using non-viral vectors and focusing on the non-invasive routes of administration.