Description

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.
The success of RNA therapy requires a multidisciplinary (molecular biology, pharmacology, chemistry, and nanotechnology) approach. RNA therapeutics should be modified to improve pharmacological properties.
First, conventional LNPs could be modified with a charge opposite to that of the therapeutic and embedded with certain chemical moieties that will help in specific targeting. Second, nuclease protection could be achieved by RNA engineering to modify the nucleotide, sugar, or backbone. Third, conjugation with carbohydrate, lipid, antibody, or peptide would help with not only stabilizing but also targeting. Fourth, DNA origami, spherical nucleic acids, and stimuli-responsive nucleic acids offer ways to circumvent challenges.

The research is intended to answer the following questions:
What are the driving factors for RNA delivery?
What are the emerging delivery and stabilization technologies for RNA therapeutics?
What challenges and impediments remain to the adoption of RNA therapeutics?
What initiatives are industry participants undertaking to accelerate adoption?
What are the specialized RNA delivery platforms that can achieve desired business outcomes, compared to naked RNA delivery?