In the last decade, there has been an encouraging shift in research, clinical development, and commercial activity to exploit the many biological roles of ribonucleic acid (RNA) for use in medicine. RNA technology provides an innovative approach to developing drugs against difficult or challenging therapeutic targets, holding potential across many diseases ranging from the largest global health challenges to extremely rare diseases.
However, RNA medicine has faced many challenges: RNA molecules are relatively unstable and transient, the limited translation into cellular protein expression can hinder efficacy, and foreign RNA molecules often trigger immunogenicity. Furthermore, the delivery of RNA molecules can be a challenge due to their relatively large size and high electric charge.
Some of these practical problems can be mitigated by chemically modifying the RNA, providing the opportunity to develop therapeutics that are more stable, effective, and tolerable for patients. The recent success of mRNA vaccines against COVID-19 and the approval of new RNA-based drugs has provided new momentum to the field, building on the key milestones and achievements of the last 60 years. Advances in our understanding of RNA structure and function, combined with a robust production pipeline, have substantially increased the capacity to develop clinically effective RNA-related applications.
In this white paper, CAS used data from the CAS Content CollectionTM—the largest human-curated collection of published scientific knowledge—to review publication trends in RNA research, the application of RNA in medicine and the use of chemical modifications and nanotechnology to improve the delivery and efficacy of RNA pharmaceuticals. The white paper focuses on chemical modifications to the nucleic acid base, backbone, and sugar molecules to increase RNA stability, along with the new delivery systems that are critical to the success of RNA medicine.
