Pharma is betting big on circular RNA to be the next generation of therapies. Here is, in a nutshell, why you should keep an eye on this exciting technology.
Showcasing remarkable flexibility and adaptability throughout COVID-19, mRNA paved the way for a long-lasting success in vaccinology. Yet the technology has its limitations: it’s short-lived and unstable. Fortunately Pharma has found a new jewel in an old pile of junk—circular RNA—and it might be the next big thing.
Saving thousands of lives during the pandemic, setting records for the highest-grossing drug launches in history and recently awarded with a Nobel prize, mRNA was undoubtedly Pharma’s champion for the past 3 years.
But while it has proved its worth in vaccinology—where short-lived protein expression triggers the desired immune response—mRNA's inherent characteristic of rapid degradation within the targeted cell limits its applications to mostly vaccines.
Circular-shaped RNA or circRNA, however, can overcome the stability limitations of linear RNA.
What is circular RNA?
First discovered in the 1970s, circular RNA was long considered as a functionless “junk” by the scientific community. That was until the advent of high-throughput RNA sequencing technologies shed light on the prevalent role it played in gene expression.
Since then, scientists have been exploring the diverse functions of circRNAs and the discoveries just kept coming—turning those old RNA rings into Pharma’s new jewel.
By joining its ends together—typically through enzyme or chemical-based ligation methods in current manufacturing processes—circRNAs can form covalently-closed loops.
A unique shape that allows them to resist exonuclease digestion and enhances their pharmaceutical stability—ultimately leading to much longer half-life, stronger and prolonged therapeutic effects for patients.
Circular RNA therapeutics are on the way
With the promise of being cheaper, more efficient, and with potential applications in countless disease areas—like oncology, autoimmunity, genetic disorders or infectious disease—unprecedented attention is drawn on circular RNA.
A growing number of Biotech companies are launching circRNA programs and major industry players are betting big on it to be the next generation of therapies.
Orna Therapeutics, an MIT spin-off developing fully engineered circular RNA therapeutics, has received a massive $ 371Mn investment to finance its lead program in 2022 [1]—including a $ 150Mn upfront from Merck.
Contract Service Providers now begin to respond to the increasing demand from sponsors. US and European players have recently added custom-made circRNA production for use in preclinical applications to their service portfolio [2].
Shunned for almost four decades, circRNA is now considered to be one of the most exciting research fields by the scientific community. An ever-growing interest reflected by the dramatic surge in related publications—the latter have been multiplied by 8 from 2017 to 2023 [3].
Although no major clinical trials are underway—yet—players from all sides of Pharma are invested to harness its potential. Potentially emerging as the preferred RNA platform for Pharma and presenting a realm of opportunities, Circular RNA’s transition into commercial may not be so distant on the horizon.
[1] Source : Orna Therapeutics. 2022, August 16. [Press release].
https://www.ornatx.com/orna-rounds-up-371m-via-series-b-deal-with-merck-for-circular-rnas/
[2] Source : Lensource® BI Platform
https://www.larka.com/en/tech-ops-outsourcing/sourcing-and-external-supply
[3] Source: PubMed