Researchers target choke point in RNA revolution

An Australian university has assembled an interdisciplinary “dream team” to tackle the mundane supply issue threatening one of the most vaunted frontiers of biomedical research.

Monash University laboratory leaders in areas as disparate as bioinformatics, chemistry, structural biology and X-ray crystallography have banded together to find new ways of synthesising ribonucleic acid, or RNA, in large volumes.

The research aims to meet worldwide demand for a raw material considered of little medical value until University of Pennsylvania biochemist Katalin Karikó discovered how to circumvent the human immune system’s rejection of injected RNA.

Her work spawned an emphatic proof of concept when Moderna and BioNTech, two companies that had supported her laboratory, developed vaccinations in record time to spearhead the world’s defences against Covid-19.

Researchers around the world are now scrambling to harness RNA’s extraordinary potential in medicine, agriculture and biosensing. Vaccines are being developed against diseases including influenza, malaria, Zika, rabies, hepatitis C, herpes, dengue fever, HIV and cancer.

RNA therapeutics are already used to prevent or treat forms of muscular dystrophy and to lower cholesterol, with hopes to extend this to asthma, cystic fibrosis and chronic obstructive pulmonary disease.

Other potential applications include slowing down the ageing process by extending the protective caps on chromosomes, and deploying personalised therapies to combat rare genetic diseases or stop tumours replicating. In agriculture, RNA could be used in animal vaccines and as an alternative to genetic modification of plants.

Australia has joined the global race to bankroll RNA research and development. In May the federal government announced an “approach to market” inviting companies to work with Canberra in developing vaccine manufacturing capabilities in Australia.

The Victorian government earmarked A$50 million (£27 million) for mRNA Victoria, a new body charged with building the state’s manufacturing capability. It has already allocated A$5 million to Monash and the Doherty Institute to manufacture batches of a second-generation Covid-19 vaccine for clinical trials.

The New South Wales government is supporting a A$15 million RNA Production and Research Network, while UNSW Sydney has committed A$25 million to its own RNA Institute. Australian biotechnology giant CSL is focusing on RNA-based influenza vaccines through its subsidiary Seqirus.   

But Monash’s head of RNA research Traude Beilharz warned that a missing “base layer” would hamper progress. She said that the world had been wrong-footed by the unexpected success of RNA vaccines and lacked the capacity to manufacture RNA on an industrial scale.

Dr Beilharz said that test tube techniques for producing laboratory quantities had not changed in three decades. “To make enough to inject a person, let alone a whole population, it’s incredibly inefficient. That fundamental part needs to catch up.”

Her group plans to use computational mining to identify new RNA-producing enzymes, and synthetic biology to harness them as microscopic biological factories. “We’ve assembled people who don’t normally work together to ask…how can we underpin this booming need the world will have for new enzymes and modified nucleotides,” she said. “Nature has already solved this problem.”

Dr Beilharz warned that a funding blind spot could hamper “the most essential work right now”, with the development of RNA-producing enzymes deemed too “unsexy” to win competitive funding bids. She also cautioned against an exclusive focus on messenger RNA, with many other forms – including antisense oligonucleotides, small interfering RNAs and other non-coding RNAs – harbouring extraordinary therapeutic potential.

john.ross@timeshighereducation.com