Inhaled nucleic acid therapeutics and vaccines

Abstract

Various strategies exist to use nucleic acids, such as plasmid DNA, antisense oligonucleotides, small interfering RNA (siRNA) and microRNA (miRNA), to manipulate gene expression as a means to treat respiratory diseases such as cancer, lung infections and asthma. Moreover, nucleic acids such as DNA and messenger RNA (mRNA) can also be used as vaccines by encoding antigen to elicit a specific immune response. Exciting gene-editing platforms based on CRISPR have emerged as potential powerful therapeutics. These nucleic acid-based therapeutics have immense potential to treat diseases that are otherwise ‘undruggable’ with small drug molecules or other biologics. Nonetheless, their high molecular weight and highly negatively charged characteristic are at odds with the efficiency of transit various epithelial/endothelial barriers to reach their target sites. The objective of this presentation is 3-fold: (1) to describe the barriers to pulmonary nucleic acid delivery and how they may be overcome through delivery system design; (2) to describe peptide based delivery system for pulmonary nucleic acid delivery; and (3) to report on the use of spray drying and spray freeze drying technologies to produce highly dispersed powder formulation of nucleic acid for inhalation.