The concepts of developing RNAs as new molecular entities for
therapies have arisen again and again since the discoveries of antisense RNAs, direct
RNA-
protein interactions, functional noncoding RNAs, and
RNA-directed gene editing. The feasibility was demonstrated with the development and utilization of synthetic
RNA agents to selectively control target gene expression, modulate
protein functions or alter the genome to manage diseases. Rather, RNAs are labile to degradation and cannot cross cell membrane barriers, making it hard to develop
RNA medications. With the development of viable
RNA technologies, such as chemistry and pharmaceutics, eight
antisense oligonucleotides (ASOs) (
fomivirsen,
mipomersen,
eteplirsen,
nusinersen,
inotersen,
golodirsen,
viltolarsen and
casimersen), one aptamer (
pegaptanib), and three small interfering RNAs (siRNAs) (
patisiran,
givosiran and
lumasiran) have been approved by the United States Food and Drug Administration (FDA) for
therapies, and two
mRNA vaccines (
BNT162b2 and
mRNA-1273) under Emergency Use Authorization for the prevention of
COVID-19. Therefore, RNAs have become a great addition to small molecules,
proteins/
antibodies, and cell-based modalities to improve the public health. In this article, we first summarize the general characteristics of therapeutic
RNA agents, including chemistry, common delivery strategies, mechanisms of actions, and safety. By overviewing individual
RNA medications and
vaccines approved by the FDA and some agents under development, we illustrate the unique compositions and pharmacological actions of
RNA products. A new era of
RNA research and development will likely lead to commercialization of more
RNA agents for medical use, expanding the range of therapeutic targets and increasing the diversity of molecular modalities.