Research Overview

RNA therapeutics is a rapidly expanding field of next-generation medicine. RNA therapy typically comprises 4 different classes of molecules: non-codingRNA (ncRNA), antisense oligonucleotide (ASO), messengerRNA (mRNA), and RNA aptamer.

Small ncRNAs are like a double-edged sword; they can either up- or down-regulate specific genes. Contrarily, long ncRNA can act as miRNA cushions, thereby indirectly affecting the gene expression. Both small and long ncRNAs have been shown to be essential in the treatment of cancer and infectious diseases. They could be easily designed for both druggable and non-druggable targets of small-molecule drugs. ASOs are typically single stranded and exhibit the characteristics of small ncRNAs. mRNA is being used as a vaccine candidate in the last two years, rather than drug molecules. RNA aptamers typically bind to protein molecules, thereby directly influencing their function.

Though RNA therapeutics offers several advantages, industry uptake of this technology has been low because the polyanionic molecules of RNA can quickly degrade, making delivery to a specific tissue or organ, absorption or endocytosis, and renal clearance major challenges. However, academic researchers and small- to mid-size companies have persisted in their efforts to develop stabilization and delivery technologies for RNA therapeutics. Current RNA delivery technologies are of two types: bioconjugation and lipid nanoparticles (LNPs). In bioconjugation, the RNA therapeutic molecule is anchored to a biological moiety, which could be carbohydrate, lipid, peptide, or antibodies. LNPs could be lipoplexes, liposomes, or exosomes. Although bioconjugation is mostly used for stabilization and delivery, LNP-based delivery has garnered the attention of many researchers and companies because of its ease of manufacturing and success of delivery. Other delivery technologies or methods, such as DNA nanostructures, spherical nucleic acids, and stimuli-responsive chemistry are in the early stage of development.