What comes after mRNA? Self-amplified RNA, states industry report

As firms look beyond COVID-19, one of the most promising platforms is self-amplifying RNAs, says a report from Clarivate.

The report by Clarivate, entitled “Where pharma are investing for the future of medicine”, said messenger RNA (mRNA) COVID-19 vaccines demonstrated “proof of concept for the technology” with BioNTech/Pfizer and Moderna releasing their  respective COVID-19 vaccines in 2020 and 2021.

As life returns to normal, pandemic-related orders for COVID-19 vaccines have dropped in size –  Pfizer, for example, reported a 26% drop in  Comirnaty in the first quarter of 2023.

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With this in mind, “it is no surprise that pharma is keen to access next generation RNA platforms that can overcome some of mRNA’s limitations, including getting the therapeutic to the desired tissue, at the right concentrations, while limiting toxic effects,” the report said.

In February 2023, Moderna announced it would continue to use Personalis’ NeXT platform in its upcoming clinical trial of mRNA-4157/V940, an investigational personalized cancer vaccine. And one month before, the firm partnered with CytomX Therapeutics for oncology and non-oncology conditions.

In January 2022, BioNTech and Pfizer inked their third mRNA collaboration to produce a vaccine for shingles (herpes zoster) using BioNTech’s proprietary mRNA technology and Pfizer’s antigen technology.

In November 2022, CSL Seqirus said it would access Arcturus Therapeutics’ late-stage self-amplifying mRNA (sa-mRNA) vaccine platform technology to support the research, development, production, and commercialization of vaccines for SARS-CoV-2, as well as influenza, pandemic preparedness, and a further three global respiratory infectious diseases.

This deal was described by Clarivate  as “the most valuable RNA platform partnership” and commented Seqirus paid “Arcturus $200 million up front and offer more than $4 billion in potential development and commercial milestones.”

Speaking to BioProcess Insider in August 2021, Roberta Duncan, Seqirus’ VP of mRNA Program Lead said  lauded  sa-mRNA as the next generation version of mRNA technology,” Roberta Duncan, Seqirus’ VP of mRNA Program Lead told

“Sa-mRNA also gives the body instructions to replicate mRNA, amplifying the amount of protein made, with the potential to use less antigen. In preclinical research, sa-mRNA technology demonstrated the potential to raise stronger cellular responses and generate significantly higher antibody titers at the same dose level as mRNA.”

Seqirus is not the only company to invest in the sa-mRNA space. Service provider Charles River Laboratories signed a deal in June 2022 to manufacture plasmid DNA-based starting materials to support Ziphius Vaccines’ Sa-mRNA candidates.

Another RNA technology the report said is “getting traction”  is circular RNA. An advantage of this type of technology is it has “the potential for being more stable than regular RNA because cellular nucleases that attack linear RNA from the ends are unable to do so.”

In August 2022 Merck & Co. (known as MSD outside of the US and Canada) announced it would  make an upfront payment of $150 million to circular RNA therapy firm Orna to discover, drive, and commercialize different programs.

Meanwhile, Ginkgo Bioworks acquired Circularis and its circular RNA technology in October 2022 to support growing demand for nucleic acid and advanced therapy services.