ASGCT: Ring's 'new class of viral vector' is re-dosable in primates, overcoming key challenge of AAVs

It was the summer of 2020. Pandemic aside, things were going well for Tuyen Ong, M.D. The physician and biotech entrepreneur was heading up the opthamology franchise unit of Biogen following its acquisition of biotech Nightstar Therapeutics, where, as chief development officer, he had led development of new adeno-associated viral vectors for delivering gene therapies.

An image of Ring Therapeutics CEO Tuyen Ong holding a 3D model of the company's Anellovectors at the ASGCT's 2024 annual meeting. He has described the vector as working a bit like the Death Star from Star Wars, with modular layers that click into place.
Tuyen Ong, M.D., holds a 3D model of the company's Anellovectors at the ASGCT's 2024 annual meeting in Baltimore. He has described the vector as working a bit like the Death Star from "Star Wars," with modular layers that click into place. (Ring Therapeutics)

“I was having a pretty good life, to be honest,” Ong recalled to Fierce Biotech Research in an interview. “From a personal standpoint, COVID had allowed me to spend more time with the family. So I wasn’t really interested in moving on.”

That changed after a conversation with Avak Kahvejian, Ph.D., general partner at biotech incubator and venture capital firm Flagship Pioneering. Kahvejian told Ong that one of the firm’s companies, Ring Therapeutics, was exploring ways to harness a family of benign, human-dwelling viruses called anelloviruses and use them as viral vectors for gene therapy, a potential way to circumvent the challenges that come with using AAVs. 

Intrigued, Ong agreed to join Ring as CEO. About four years later, on May 8, the company revealed data at the 2024 American Society for Gene and Cell Therapy (ASGCT) meeting showing that Ring’s so-called Anellovectors—a viral vector based on the anellovirus—can express genes in the retinas of primates and be dosed more than once, overcoming a major hurdle to the broader applications for gene therapies. The work is part of broader investigational new drug-enabling studies, including work in mice, that will help the company make the case for testing in humans. 

“We’re trying to create a new class of viral vector,” Ong said. “No one’s done this since AAV.”


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AAVs are the most commonly used viral vectors for gene therapy, but they can’t penetrate every tissue—in other words, they have limited tropism, which also limits the conditions they can be used to treat. On top of that, most people already have antibodies to some type of AAV, including the one most commonly used for gene therapy, AAV2. And if they don’t have antibodies before they undergo gene therapy, they will after, which is why such treatments can only be done once. 

Those issues have hamstrung the indications for gene therapy. And, while researchers and biotechs are exploring alternatives like lipid nanoparticles and engineered AAV capsids, these come with challenges of their own. 

The anellovirus, meanwhile, seems to have few downsides so far. The vast majority of humans—perhaps even all of us—carry at least one type of them. No disease has been unequivocally associated with them so far, though there is some evidence that they might be indirectly involved with instigating or worsening some viral illnesses. And, while they do interact with the immune system, they don’t do so in a way that causes outright rejection. They also have very high tropism—they’re found in the blood and most organs throughout the body.

But if the human anellovirus was always an option for viral vectors, why hasn’t anyone tried it yet? The answer might be as simple as an information vacuum. According to Ong, there was a time when researchers were attracted to the idea of studying anelloviruses. But because no one could link them to a disease, interest dried up and took funding with it. 

“Most virologists view viruses as a research tool in regards to what diseases they are associated with,” Ong said. “Nobody could find an association between the anellovirus and a disease.” 

Prior to Ring’s founding, Kahvejian and others at Flagship’s incubator, Flagship Labs, rediscovered anelloviruses by using a special platform to mine the human commensal virome, the ecosystem of benign viruses that make their home in the body. Thanks to that platform, now called Anellogy, the team became the first to discover the virus’s structure, synthesize it, remove its “guts,” turn it into a vector and test it in animals.

Ring was founded in 2017. The original Anellovector was created around 2019. Four years later, the company is testing them in primates—a far faster timeline than with AAVs, which took 15 years to go from vectorization to primates. While that’s partly because the AAV research was pioneering work, Ong said, the Anellogy platform certainly helps speed things up. 

“We’ve had to create all of that science,” Ong said. “A big part of that is being able to build the platform to enable that, which is how we managed to do it so quickly.” 

In the primate studies that produced the new data shared at ASGCT, the researchers injected Anellovectors containing a glowing transgene into the vitreous humor of the animals’ eyes. After seeing that the vectors had infected the retina and expressed the gene, they injected another round at a higher dose. Gene expression rose accordingly without any signs of toxicity—a clear signal that the technology worked. While work in the primates is still ongoing, the researchers have evidence from mouse models that gene expression continues for at least 12 months. 

“We have all the big ingredients and the foundations of, hopefully, something that is very impactful and meaningful for patients,” Ong said. 

Now that the Anellovectors appear to work in nonhuman primates, Ring is thinking about the most efficient path toward commercialization. That means being strategic about indications and what to try next with the technology—such as bigger payloads, which the Anellovectors appear to be able to handle, according to a poster Ring presented at ASGCT. 

“There’s so much possibility with the Anellovectors—it can get to different tissues, you can put in different payloads, you can put in potentially larger payloads,” Ong said. “So my job is to try to unlock all of that but to do it in a way that is strategically mindful that we are taking a relatively rapid path to the clinic.”

If all goes according to plan, Anellovectors will first make their mark in an eye condition called wet macular degeneration, an age-related condition where leaky blood vessels cause sight loss. The current treatment is regular injections of an anti-VEGF protein, which slows vision decline by keeping blood vessels from growing too quickly. It works, but patients have to get injections on a regular basis. 

Advertum, Regenxbio and 4D Molecular Therapies all have gene therapies in the clinic for the condition, too, but none have crossed the FDA finish line yet. A close look at their data shows that the patients in these trials often still need anti-VEGF injections or rescue therapy around the six-month mark, Ong said. 

“What we have is an opportunity to be not only a safer, less inflammatory drug in the eye, but we could also dose titrate and re-dose if need be so we can deliver the right levels of that anti-VEGF protein,” he explained. “That really allows us to differentiate, and then with the potential low cost of goods, to be able to have much wider access to this.”