Highlights
- COPD is the third leading cause of death globally, and there is an urgent unmet medical need to develop novel therapeutics specifically for COPD.
- Numerous ncRNAs like miRNAs, lncRNAs, and circRNAs, have been linked to COPD. Few of these dysregulated ncRNAs have been functionally characterized. Some ncRNA targets including miR-195, miR-181c, and TUG1 have shown promise in mitigating COPD in vivo.
- Significant effort has been made to develop siRNA therapeutics targeting mRNAs critical for the pathogenesis of COPD. siRNAs targeting RIP2, RPS3, MAP3K19, and CHST3 mRNAs have been successfully validated in in vivo COPD models.
- Direct inhalation of RNA therapeutics to the lungs is the best route of administration for COPD. Innovative approaches to enhance RNA stability, tissue targeting, cell penetration and intracellular endosomal escape are critical to realize the full potentials of RNA drugs.
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation with persistent respiratory symptoms. Current therapeutics for COPD are largely borrowed from the drug armamentarium for the treatment of asthma, which has different pathophysiological mechanisms from COPD. COPD has been linked to dysregulated expression of mRNAs and noncoding (nc)RNAs including miRNAs, PIWI-interacting (pi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs. This review highlights and discusses some recent advances towards development of RNA therapeutics for COPD.
