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.
It is claimed to have longer-lasting therapeutic effects than traditional RNA, but at lower doses.
Arcturus Therapeutics, which is currently developing the self-replicating vaccine COVID-19, has just completed Phase 3 trials in Vietnam. It is also testing the shot in Singapore as a third dose booster for the Pfizer vaccine.
Replicate Bioscience, a San Diego-based startup, is using the technology to develop treatments against cancers and other noninfectious diseases. The company is planning to launch clinical trials in the next year.
Moderna and Pfizer’s COVID-19 vaccines temporarily turn cells into small drug factories by inserting RNA instructions into them. For approximately two days, the cells produce proteins that train the immune system.
The process of replicating RNA works the same way but directs factories to create an additional molecule. The factory is then able to keep producing for several months or weeks by using the additional molecule, an enzyme.
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. It is taught. 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.
Because it uses a lower dose, the technology can help reduce side effects. Moderna’s vaccine uses 100 micrograms of RNA per dose. Pfizer’s vaccine contains 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. Now that they have figured out how to get the RNA into nanoparticles, manufacturing on a mass scale should be much easier than with conventional RNA.
Replicate Bioscience is taking a different approach. 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.
In the second half next year, the company hopes to have one or more of its investigational drug in clinical trials.
This story was originally published by Derek Staahl on Scripps station KGTV in San Diego.