Image-guided hydrodynamic gene delivery to the liver: Toward clinical applications

Abstract

Various metabolic and monogenic diseases have genetic defects in the liver and are often caused by lack or overproduction of a critical gene product in its cells. Conventional therapeutic methods are often insuffi cient or unavailable to manage genetic diseases in the liver; therefore, more effi cient strategies are urgently needed. Gene therapy emerged as novel method of treatment relying on liverdirected transfer of a gene-coding sequence to produce the missing gene products or a nucleic acid sequence to inhibit the production of the gene product in excess. Practically, the success of the nucleic acid-based approaches is dependent on the availability of a method capable of delivering the gene or nucleic acid therapeutics to liver cells. Various methods of gene delivery have been developed, including viral methods and nonviral methods comprising synthetic vectors and physical methods. Hydrodynamic gene delivery is among the most effi cient and the most commonly used method for liver-directed gene delivery. Here we will briefl y summarize the principles and the progress that have been made in hydrodynamic gene delivery toward clinical applications.