Nucleic Acid Drugs—Current Status, Issues, and Expectations for Exosomes

SIMPLE SUMMARY: Nucleic acid drugs provide novel therapeutic modalities with characteristics that differ from those of small molecules and antibodies. In this review, I focus on the various mechanisms through which nucleic acid drugs act on, the status of their clinical development, and discuss several hurdles that need to be surmounted. In addition, by listing examples of how the progress in exosome biology can lead to the solution of problems in nucleic acid drug therapy, I hope that many more nucleic acid drugs including anticancer drugs will be developed in the future. ABSTRACT: Nucleic acid drugs are being developed as novel therapeutic modalities. They have great potential to treat human diseases such as cancers, viral infections, and genetic disorders due to unique characteristics that make it possible to approach undruggable targets using classical small molecule or protein/antibody-based biologics. In this review, I describe the advantages, classification, and clinical status of nucleic acid therapeutics. To date, more than 10 products have been launched, and many products have been tested in clinics. To promote the use of nucleic acid therapeutics such as antibodies, several hurdles need to be surmounted. The most important issue is the delivery of nucleic acids and several other challenges have been reported. Recent advanced delivery platforms are lipid nanoparticles and ligand conjugation approaches. With the progress of exosome biology, exosomes are expected to contribute to the solution of various problems associated with nucleic acid drugs.