The progress and promise of RNA medicine—an arsenal of targeted treatments

Abstract

In the last decade, there has been a shift in research, clinical development, and commercial activity to exploit the many roles of RNA in physiology for use in medicine. With the rapid success in the development of lipid-RNA nanoparticles for mRNA vaccines against COVID-19 and with several approved RNA-based drugs, RNA has catapulted to the forefront of drug research. With diverse functions beyond the role of mRNA in producing antigens or therapeutic proteins, many classes of RNA serve a regulatory role in cells and tissues. These RNAs have potential as new therapeutics, with the RNA itself serving as either a drug or a target. These new types of RNA drugs require a plethora of modification chemistries to improve their therapeutic benefit. We describe the current state of the art for RNA medicine. Using the CAS Content Collection data, we examine the publication trends covering the roles of RNA in the cell, the application of RNA in medicine, and the use of chemical modifications and nanotechnology to deliver effective RNA pharmaceuticals to their cellular targets. This review reveals the sustained global effort that propelled this field to the cusp of realization for novel medical applications of RNA in many diseases. It serves as an easy-to-understand overview so that scientists from many different disciplines can appreciate the current state of the field of RNA medicine and join in solving the remaining challenges for fulfilling its potential.

Exosomes─Nature’s Lipid Nanoparticles, a Rising Star in Drug Delivery and Diagnostics

“…The exosome-mediated RNA transfer has been initially reported for mRNAs and miRNAs. 32,33,148,1494,149,150 Exosomal RNA pools are enriched in small non-coding RNAs (sncRNAs) and differ from the cellular RNA profile. 72,151,152 A wide variety of RNA species are embedded in the extracellular vesicles.…”

“…Annual distribution of the RNA-related documents within the pool of publications concerning exosome applications in therapy and diagnostics shows an explosive growth in the last 2−3 years for all RNA types (Figure 13B), which is impressive, even considering the overall rapid growth in interest in all RNA medicines. 150 Glycoconjugates. Polysaccharides and glycans are other exosomal constituents located on their outer surface.…”

Artificial genetic polymers against human pathologies

“…For these reasons, major successes with therapeutic oligonucleotides are limited to those used in local delivery (for example, to the eye), and to the liver. Excellent reviews may be useful for in-depth reading [154,155].…”

Atomistic Insights into Organization of RNA-Loaded Lipid Nanoparticles

“…1−3 Nearly 800 million doses (September 2022) of messenger RNA-based (mRNA) vaccines have been administered in the European Union to date. 4 However, RNA-based medicines are not only useful for vaccination purposes 5 but offer new strategies for the treatment of cancer 6,7 and rare diseases. 8 Progress in RNA-based therapies has been hampered by the fact that RNA molecules are very fragile and cannot directly enter targeted cells due to their size and charge.…”