Drugmakers are already developing the next generation of mRNA vaccines

Companies developing self-replicating RNA
Arcturus Therapeutics and Replicate Bioscience are developing self-replicating RNA
Posted at 9:10 AM, Sep 30, 2021

SAN DIEGO — After the success of the mRNA COVID-19 vaccines made by Pfizer and Moderna, some San Diego-based companies are developing the next generation of the technology, called self-replicating RNA.

Developers say it offers longer-lasting therapeutic effects than conventional RNA at lower doses.

Arcturus Therapeutics is developing a self-replicating mRNA COVID-19 vaccine that just entered Phase 3 trials in Vietnam. The company is also testing its shot as a third dose booster to the Pfizer vaccine in Singapore.

A new San Diego-based startup called Replicate Bioscience is harnessing the technology to develop treatments for cancers and other non-infectious diseases. The company hopes to launch clinical trials next year.

The COVID-19 vaccines from Pfizer and Moderna work by introducing strands of RNA instructions into cells, temporarily turning the cells into tiny drug factories. The cells churn out proteins to train the immune system, called antigens, for about two days before the factories shut down.

Replicating RNA works in a similar way, but it directs the factories to make an additional molecule. That molecule, an enzyme, fires the factory back up so it can keep production going for weeks or months.

In the case of Arcturus, the company’s self-replicating COVID-19 vaccine prompts cells to produce immune-training proteins for about two weeks, said CEO Joe Payne.

“You need a vaccine that expresses the antigen for an extended period of time, so the body sees it, sees it again. Learns it. Memorizes it. Never forgets it,” Payne said.

That repetition should produce stronger and longer-lasting protection, Payne said, although the company won’t know for certain until it completes clinical trials.

The technology can also help mitigate side effects because it works at a much lower dose. Moderna’s vaccine uses 100 micrograms of RNA per dose. The Pfizer vaccine uses 30 micrograms. Arcturus’ self-replicating vaccine uses five micrograms of RNA.

“Less allergic responses, for example,” Payne said. “Less undesirable adverse events.”

Payne said the self-replicating RNA vaccines took longer to develop because the molecules are about three times larger than conventional RNA, making the manufacturing process more complex. But now that the company has figured out how to coil the RNA to fit into tiny nanoparticles, he said manufacturing on a mass scale should be easier than conventional RNA because they require so much less material.

Replicate Bioscience is going in a different direction. The new startup just got a $40 million investment to develop self-replicating RNA medicines to treat breast cancer, lung cancer, tumors that don’t respond to drugs and autoimmune diseases.

“The Moderna and the Pfizer-BioNTech vaccines have really put the promise of the technology out there, and there’s a slate of new companies that are looking to really deliver on that promise,” said Replicate CEO Nathaniel Wang.

Wang said the company’s self-replicating technology turns cells into drug factories for about two months.

“That means less injections for the patients and a much longer time to get a therapeutic effect,” he said. “That’s why you can really open up new areas that you can treat patients with because of the longer expression.”

Replicate’s platform allows for an even lower dose of RNA. They’re currently operating with concentrations about 1,000 times less than Moderna’s COVID-19 vaccine, Wang said.

The company is hoping to get one or more of its investigational drugs into clinical trials in the second half of next year.

This story was originally published by Derek Staahl on Scripps station KGTV in San Diego.