The Nobel Prize in Medicine has been awarded to Victor Ambros and Gary Ruvkun who discovered microRNA and its role in the regulation of genes.

The two scientists discovered a new principle of gene regulation that is contributing to the development of drugs to treat cancer and heart disease, as well as neurological conditions such as Alzheimer’s disease and Parkinson’s disease.

The So What

“It’s time for major pharma companies to double down on building knowledge and capabilities, and consider acquiring licenses for drugs and clinical-stage assets that have shown promise to impact large populations,” says Jorge Vazquez Anderson, a partner at BCG who is also an RNA scientist.

“Many major pharma companies have already invested, it is time for them to do it more decisively.”

Novel therapies and medicines typically begin by tackling rare diseases, and RNA therapies have followed this pattern.

There are already existing RNA technologies that are commercially viable and in use:

• The best known—messenger RNAs—were used in the COVID vaccines produced by Moderna and by Pfizer and BioNTech.
• Biopharma firms such as Alnylam and Ionis are leading on small interference RNA to help cure rare hereditary diseases or genetic birth defects such as spinal muscular atrophy or amyloidosis.

The COVID vaccines helped establish broader proof of efficacy and safety, and RNA-based therapies are now starting to address diseases that impact much larger numbers of people.

MicroRNA is a subset of other RNA technologies and an example of the acceleration of the RNA innovation wave.

Clinical trials of treatments based on microRNA are already in progress for cancer, heart disease, and neurodegenerative disorders.

RNA is the ribonucleic acid present in living cells that carries instructions coded in DNA to make proteins. Until recently, it was considered a mere messenger, but now many regulatory functions have been discovered too. MicroRNAs as therapeutics agents are an example of harnessing these regulatory properties. MicroRNAs can disrupt a disease from damaging or distorting cells by binding to messenger RNAs.

“MicroRNA takes the efficacy of potential drugs to the next level by tackling multiple genes at once,” says BCG Managing Director and Partner Shana Topp who specializes in cell and gene therapy manufacturing.

“RNA also has other advantages over other gene therapies: It is simpler from a manufacturing standpoint. And, as demonstrated by the rapid development of COVID vaccines, it is easier and simpler to predict how an RNA molecule will behave. This can accelerate lead times to design and develop drugs.”

Now What

There are three key challenges when working specifically with microRNAs:

• Delivery systems. Efficiently delivering microRNA-based therapies to specific tissues or cells without inadvertently affecting other areas.
• Stability. MicroRNAs being used as treatment need to be stable in the body and resist enzymatic degradation. RNA-based molecules are much less stable than DNA or proteins.
• Safety. Minimizing unintended interactions and immune responses is critical for clinical success. Unintended interactions are more likely because of potential binding given weaker attraction to other molecules with sequence similarities.

These challenges have two major implications for drug development and manufacturing:

• Design. The function of the RNA depends on the sequencing of the units within, including the way RNA molecules fold into specific 3D structures. A deep understanding of the role of sequence and structure of the RNAs, including chemical modifications, will be needed to better control unintended interactions.
• Delivery systems. There needs to be continued innovation on more efficient delivery systems such as lipid nanoparticles—layers of fat that build a protective shell around the microRNA to protect it from degradation while reaching its target. Viral vectors, which use modified viruses to deliver microRNA to cells, is another potential solution.

“Specialist firms are leading the way at present, especially when it comes to IP, talent, and development knowhow,” Topp says.

“To take advantage of this wave of innovation, industry players should develop a strategy to build the required capabilities, either through acquisitions, partnerships, or internal investments.”