Paving the Road for RNA Therapeutics

Abstract

Therapeutic RNA molecules possess high potential for treating medical conditions if they can successfully reach the target cell upon administration. However, unmodified RNA molecules are rapidly degraded and cleared from the circulation. In addition, their large size and negative charge complicates their passing through the cell membrane. The difficulty of RNA therapy, therefore, lies in the efficient intracellular delivery of intact RNA molecules to the tissue of interest without inducing adverse effects. Here, we outline the recent developments in therapeutic RNA delivery and discuss the wide potential in manipulating the function of cells with RNAs. The focus is not only on the variety of delivery strategies but also on the versatile nature of RNA and its wide applicability. This wide applicability is especially interesting when considering the modular nature of nucleic acids. An optimal delivery vehicle, therefore, can facilitate numerous clinical applications of RNA.

Highlights

• RNA can manipulate targets that were previously undruggable by monoclonal antibodies (mAbs) or small molecules.

• RNA therapy is a safer alternative to DNA therapy and is versatile as it can either increase or decrease gene expression in order to introduce new transcripts for protein replacement therapy and more.

• Clinical translation of RNA therapeutics has accelerated in recent years.

• Chemical manipulation of RNA molecules render them more stable and hence increase their potency and applicability.

• Various carriers for the in vivo delivery of RNA molecules have been invented that include antibody–RNA conjugates, aptamer–RNA conjugates, lipid nanoparticles, and polymers.

• Delivery to extrahepatic tissues might require targeting moieties.