SiRNA-based therapies for pulmonary diseases.

ABSTRACT

Various delivery strategies, involving siRNA as a therapeutic tool for gene silencing, have been highlighted through several investigations all over the world. One such medical target, where the siRNA-based therapies have been immensely explored and have met with considerable success, is the area of pulmonary disorders. Lung diseases have presented themselves as attractive targets for studying siRNA-mediated cures due to their widespread persistence and lethality. Another interesting feature in this case is that the lung is accessible to therapeutic agents via multiple administration routes including the nasal, oral and intravenous routes. Recent advances in pulmonary delivery highlight the exploitation of all these routes for administration of siRNA-based therapies, particularly by employing non-viral carriers like nanoparticles. Through this manuscript we aim to provide a comprehensive overview of the most important and the latest developments in non-viral siRNA delivery for lung diseases. We have focused our discussion on the diverse systems, which have been investigated for a plethora of pulmonary disorders, ranging from inflammatory conditions like asthma and COPD, to infectious diseases like tuberculosis, and to lung cancer. An overview of the preclinical and clinical investigations conducted in this area has also been presented to the readers. While a variety of these systems have been found to be promising in pre-clinical studies, their successful transition as therapeutics will ultimately depend upon their clinical safety and efficacy, as well as the specificity of the carriers and methods employed for their administration.