Physical Methods of Gene Delivery

Gene therapy can be defined as the use of nucleic acids (NAs) as medicines with the aim of correcting a deficient gene expression, introducing new functions in the cell, repairing mutations and modulating the gene expression. Two main classes of vectors, viral and nonviral, have been used for gene delivery in order to avoid the NAs hydrolysis by tissue nucleases and improve their cellular uptake. The ideal gene delivery vector should offer high transfection efficacy, cell specificity and low toxicity. However, the immunogenic and mutagenic side effects of viral vector as well as toxicity and low efficacy of nonviral carriers are limiting their application. In this respect, naked NAs delivery by physical methods could be the safest procedure for gene therapy strategies if the appropriate efficacy can be achieved. These procedures employ physical forces to permit the nucleic acid cross the cell membrane and reach the cell without any carrier agent. Although viral and nonviral chemical methods are widely employed in experimental research and clinical trials, the physical methods of DNA delivery are a strategy in increasing progress. In this chapter, the main physical procedures (microinjection, needle injection, needle-free jet injection, gene gun, electroporation, sonoporation, hydroporation, magnetofection and laser irradiation) for naked nucleic acids delivery are described, emphasizing their use justification, their development, the proposed mechanism of NAs transfer and their clinical use or potential application.