What is therapeutic RNA?
Therapeutic RNA, a sector with multiple potential
Therapeutic RNA
In recent years, ribonucleic acid (RNA)-based therapies have become a popular topic among researchers, biotech and pharmaceutical companies. Highlighted during the COVID-19 pandemic by their accelerated development, RNA’s medical applications go far beyond vaccines.
Undeniable advantages
ndeed, unlike small molecules of chemical origin and biological drugs, RNA-based therapies offer an undeniable advantage: the theoretical possibility of targeting any protein in the body, including those previously considered undrugable targets.
RNA-based therapies have the potential to revolutionize drug development and are distinguished from other therapeutic modalities by :
- Their theoretical potential to target all proteins and biological functions
- Their rapid and straightforward development
- The small-scale infrastructure required for their production
Le développement des thérapies ARN en hausse
These attributes contribute greatly to the growing number of biotech and big pharma companies incorporating new RNA-based modalities into their product development pipeline.
Despite the recent boom in the global RNA therapeutics sector, analysts generally agree that the market for RNA therapeutics is set to soar to nearly US$40 billion by 2030.
Types of RNA-based modalities
Main RNA technologies considered for therapeutic purposes
Although the spotlight has been on messenger RNA (mRNA)-based vaccines due to the COVID-19 pandemic, there are several types of RNA-based products currently being considered for a variety of therapeutic applications.
Among the types of technologies under development, three main product families are currently on the market: antisense oligonucleotide (ASO)-based therapies, those using small interfering RNAs (siRNAs) and messenger RNA (mRNA)-based technologies.
Messenger RNA (mRNA)
Structure
Single-stranded RNA molecule containing protein-coding information
Application
Induces protein synthesis by providing instructions to the cellular machinery
MicroARN (miARN)
Structure
Single-stranded RNA molecule
Application
Regulates gene expression by binding to target mRNA and preventing translation
Ribozymes
Structure
RNA molecule with enzymatic activity
Application
Clips specific RNA molecules, targeting and inactivating disease-causing RNAs
Circular RNA (circRNA)
Structure
Single-stranded RNA molecule with covalent closed-loop structure
Application
Involved in the regulation of gene expression and may have therapeutic potential
Short interfering RNA (siRNA)
Structure
Double-stranded RNA molecule with a guide strand and a passenger strand
Application
Reduces expression of specific genes by degrading complementary mRNA molecules
Antisense oligonucleotides (ASO)
Structure
Synthetic RNA or single-stranded DNA molecule
Application
Modulates gene expression by binding to target RNA molecules, preventing translation or promoting degradation
Aptamers
Structure
Short single-stranded RNA molecule
Application
Binds to specific targets, such as proteins or cells, to modulate their activity
Long non-coding RNAs
Structure
Long, single- or double-stranded RNA molecule that does not code for a protein
Application
Involved in the regulation of gene expression and may have therapeutic potential
Main target indications
Although potentially applicable to a wide range of therapeutic indications, RNA-based products are not destined to completely replace other current therapeutic modalities such as small molecules and biologics.
They are, however, very interesting when rapid development is required, when available drugs act in a non-specific way, or in the context of pathologies for which no therapy exists, such as many rare diseases. At present, RNA-based therapies are mainly targeted at the following indications:
Infectious diseases (vaccines)
Cancer
Cardiometabolic diseases
Central nervous system disorders
Constraints currently associated with RNA technologies
While a growing number of products are being brought to clinic and to market, the indications targeted are still largely dictated by the constraints currently associated with RNA technologies. Indeed, researchers and companies involved in the development of new RNA-based therapies have to overcome the rapid degradation of the RNA molecule, the natural tropism towards the liver of the lipid nanoparticles used to transport the RNA, and the relatively high cost of scaling up production.
However, these are issues that the research community and biopharmaceutical companies are addressing with great interest, testing new and innovative ways to increase RNA stability, better direct its delivery to specific organs or cell types, and improve biomanufacturing processes to make them more cost-competitive.
