Researchers from A*STAR’s Genome Institute of Singapore (GIS) and Institute of Bioengineering and Bioimaging (IBB), along with the National University of Singapore Yong Loo Lin School of Medicine (NUS Medicine), were awarded a contract from the Wellcome Leap R3 Program to build the next generation of mRNA technology.

The R3 program has two goals: one, to increase exponentially the number of biologic products that can be designed, developed, and produced every year, reducing their costs and increasing equitable access; and two, to create a self-sustaining network of manufacturing facilities providing globally distributed, surge capacity to meet future pandemic needs.

A*STAR officials, who point out that the research will help advance the team’s focus on  COVID-19 and potential other pandemics, report that the Singapore group is the only awardee from Asia, out of seventeen teams worldwide to be awarded the contract this year.

The recent development of mRNA vaccines has revolutionized the ability to protect against
COVID-19 viruses, and opened the possibility of vaccinating on a broad scale from additional diseases, including other viral and bacterial infections, and even cancer. While highly effective, current RNA vaccine designs carry several drawbacks, including the needs for low temperatures for transport and storage and for the administration of high doses to be injected (30 to 100ug/dose), and high costs. The Singapore team’s project aims to address some of these shortcomings.

The lab of Wan Yue, PhD, has been studying RNA and developing novel technologies to study various aspects of RNA in disease and biological systems. In this research, her lab aims to leverage its expertise in RNA to develop better designs for mRNA vaccines. The team is developing circular RNA versions of the vaccine, which involves increasing and stabilizing the amount of protein produced. This would allow the dose to be reduced, in turn lowering the cost of the vaccine, according to Wan, who serves as group leader of the laboratory of RNA genomics and structure, and associate director of epigenetic and epitranscriptomic systems at GIS.

“Understanding the basic biology of RNA is key to our ability to use it as therapeutics,” she says. “Our team’s work will deepen the understanding of RNA and its ability to be delivered into human cells, enhancing its promise as medicine towards infectious diseases.”

“Safe and effective delivery is the key for successful clinical applications of nucleic acid therapeutics” adds Yang Yi Yan, PhD, covering executive director of IBB, whose team is working on biodegradable nanoparticle-based nucleic acid delivery. “In this work, IBB will make lipid nanoparticles with controlled size and surface functionality so that they can be used to deliver the novel RNA vaccines effectively and safely to lymph nodes and immune cells.”

Singapore is deeply involved in the global effort to develop RNA vaccines to fight both current and future pandemics,” notes Patrick Tan, MD, PhD, executive director of GIS.

“Through team effort across various institutes, we hope to develop low cost, effective vaccines that do not need to be injected into the body,” he says. “This is part of our GIS journey in developing world-class nucleic acid therapeutics capabilities in Singapore to build a fast and flexible system in our fight against different diseases.”