Chitosan-mediated orally delivered nucleic acids: a gutful of gene therapy

Gene therapy is rapidly gaining its hold in preclinical drug evaluation. However, upfront, ease of administration and greater patient compliance should strictly drive research efforts for developing modes of gene delivery. It has been a decade since plasmid DNA was first introduced orally in animals. Since then, two main modes of such delivery for potentially therapeutic nucleic acids, chitosan-based systems and non-chitosan-based systems, have been developed, at a steady though slow pace. This slow pace is partly due to the various hurdles faced with oral delivery, especially for labile molecules like nucleic acids. The real challenge is to enhance delivery systems that can traverse the gut and gain entry into the bloodstream in sufficient quantities for efficacy in diseased tissues at a distance. This review examines some of the current chitosan-based vehicles used for oral administration of potentially therapeutic nucleic acids, and explores novel ways to better deliver such molecules in the future for non-vaccination applications.