Is RNA therapy the future?

Alistair Gardiner | October 22, 2021

You’ve probably heard people talking about RNA therapeutics over the past year or two. In fact, there’s a good chance you’ve used this new kind of treatment—both Pfizer/BioNTech and Moderna’s COVID-19 vaccines are mRNA therapies.

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Female scientist looking through microscope with another researcher in background

The research community is excited about the prospects of RNA therapy for treating a wide variety of conditions in the future.

RNA therapeutics are a rapidly expanding class of drugs that target previously “undruggable” pathways and are part of the push to make personalized care a reality. They’re cost-effective and relatively simple to manufacture, and their versatility brings hope that they can revolutionize the treatment of ailments such as cancer, muscular dystrophy, and viral infections. 

“We are in the midst of a therapeutic revolution, the likes of which have not been seen since the advent of recombinant protein technology almost 50 years ago in Silicon Valley,” wrote the authors of a review recently published in Frontiers Bioengineering & Biotechnology. 

Here’s an overview of some of the RNA-based therapies that have already received regulatory approval or are currently being evaluated in clinical trials, plus the challenges and advantages associated with the use of RNA-based drugs, based on recent research.

RNA therapy and COVID-19 vaccines

In late 2020, Pfizer/BioNTech and Moderna’s respective COVID-19 vaccines (officially called BNT162b2 and mRNA-1273) were granted Emergency Use Authorizations by the FDA. The drug companies developed these mRNA vaccines in record-breaking time, according to a review published in the Journal of Microbiology and Biotechnology (JIMB) in August. But these were not the first RNA therapies that the FDA has reviewed.

Recent advances in the cellular delivery of RNA have led to the development of RNA-based therapeutics for a wide range of applications. The authors of the aforementioned Frontiers review explain that there are two main approaches to developing RNA drugs: antisense RNA (RNAi) and message RNA (mRNA). In short, RNAs can carry instructions for building proteins, assist in activating (or deactivating) certain genes, alter the activity of other RNAs, and play a role in chemical reactions.

The promise of RNA therapies lies in their versatility. “Advantages of RNA-based drugs that are driving development include: (1) their ability to act on targets that are otherwise “undruggable” for a small molecule or a protein; (2) their rapid and cost-effective development, by comparison to that of small molecules or recombinant proteins; (3) the ability to rapidly alter the sequence of the mRNA construct for personalized treatments or to adapt to an evolving pathogen,” the authors wrote.

Available RNA therapies

According to a review published in the Journal of Microbiology and Biotechnology in August, over the past 5 years, the FDA has approved more than 10 RNA-based drugs, while a host of others are currently deep into clinical trials or awaiting regulatory approval. These therapies are designed to treat and prevent cancers, infectious diseases, neurological disorders, and heart and metabolic diseases.

Of the 14 RNA-based FDA-approved therapeutics, only two are mRNA drugs (one of which is the aforementioned Pfizer/BioNTech vaccine). The others are largely for niche ailments. 

There are four RNA-based therapies for disease-specific mutations of Duchenne muscular dystrophy disorder; two of the drugs are for the treatment of polyneuropathy caused by hereditary transthyretin amyloidosis. Another of the available therapies is nusinersen, an RNA-based therapy that increases levels of the survival motor neuron protein as a treatment for spinal muscular atrophy.

There are also a number of RNA-based drugs that have been granted approval by other regulatory bodies, like the European Medicines Agency, but were turned down by the FDA. These include inclisiran and volanesorsen, which are available for the treatment of primary hypercholesterolemia and familial chylomicronemia syndrome, respectively, in the European Union.

Therapies in the pipeline

As noted by the authors of an article published by BCG, prior to the pandemic, RNA-therapies were focused mainly on rare genetic diseases, like Usher syndrome Type 2 or Hurler’s syndrome. But following the success of the COVID-19 vaccinations, the race is now on to use RNA therapeutics to treat more common conditions, like cancer, cardiovascular diseases, and neurological conditions. 

Cardior Pharmaceuticals is currently developing a microRNA drug that aims to treat heart disease by blocking the activity of other RNA molecules that cause cardiovascular damage. According to an article published in Labiotech, the drug has shown promise in early trials. And MiNa Therapeutics is working on an RNA drug that will activate other RNA molecules, which the firm hopes will be used to treat metabolic disease and cancer. 

There are various RNA-based vaccines in development, according to the aforementioned JIMB review. These include CureVac and Walvax’s COVID-19 vaccines, which have reached phase 3 trials. A range of mRNA therapies are in initial phases of clinical trials for cancers like advanced melanoma and non-small cell lung cancer, and several others are being developed for Zika virus, influenza, rabies, Chikungunya virus, and other viral infections. 

In addition to this, there are RNA therapies in development to treat inflammatory disorders, eye-related disorders, hepatitis B, hereditary bleeding disorders, and a range of other conditions and diseases.

Challenges ahead

While researchers and investors rush to probe the possibilities of RNA-based therapies, there are still many long-term safety hurdles and efficacy challenges to overcome. Many RNA therapies in development still exhibit poor cellular uptake and fast clearance or present side effects or instability issues. Likewise, regulatory agencies may be slower to trust new kinds of therapies without robust evidence. 

However, the development and deployment of the mRNA COVID-19 vaccines over the past year may have opened regulators’ eyes to the speed, safety, efficacy, and versatility that RNA-based therapies offer. The authors of the above Frontiers review concluded that “the solutions have advanced to the point that RNA therapeutics are now feasible.” The RNA revolution may have already started.

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