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CircRNA Breakthrough: Houston Methodist and CEPI Forge Alliance to Revolutionize Vaccine Technology

March 15, 2024 - Eden McCleskey

In an effort to advance global disease-defense technology, the Coalition for Epidemic Preparedness Innovations (CEPI) and Houston Methodist are teaming up to develop a new circular RNA vaccine platform that's more stable, durable and cost-effective than traditional mRNA vaccines. Click here to read a Politico article about the historic partnership.

The initiative, supported by CEPI funding of up to $3.8 million, aims to speed the development of the Houston Methodist vaccinology team's game-changing circRNA technology, designed to combat future epidemic and pandemic threats.

Under the leadership of Dr. John Cooke, director of Houston Methodist's Center for RNA Therapeutics, the team is focused on the design and preclinical evaluation of circular RNA vaccine candidates, initially against Chikungunya, a CEPI priority pathogen. With their initial project, they aim to generate the data necessary to establish preclinical proof of concept for the vaccine platform.

"Obviously, we've recently had a wake-up call and seen how quickly one disease can spread and stop the whole world in its tracks — even with a wildly effective vaccine, developed and distributed in record time," Dr. Cooke said. "It's vitally important that we use this time wisely to develop better, smarter and faster defense capabilities, including vaccines that last longer and are cheaper and easier to produce."

As its name implies, circular RNA technology introduces a closed-loop RNA structure, potentially offering enhanced stability, durability and cost-effectiveness compared to linear mRNA candidates. The Houston Methodist Research Institute's circRNA platform was developed by faculty member Dr. Dan Kiss, who identified a novel method to produce circular RNA in vitro.

Although the platform is still in early stages, it holds the promise for single-dose regimens, reduced RNA amounts per dose, lower costs and increased accessibility while avoiding the need for elaborate cold-chain storage.

In addition to working on the CEPI initiative, Dr. Kiss's lab continues to advance the circRNA technology by investigating its application in vaccines (COVID-19, TB and Mpox), different cancers and even genetic diseases.

"Despite being once thought of as molecular junk, recent research has suggested that, with its stable looped structure, circular RNA could be harnessed for RNA-based medicines," Dr. In-Kyu Yoon, acting executive director of Vaccine R&D at CEPI, said in a recent press release announcing the grant. "If effective, these circRNA vaccines could progress this new scientific era of mRNA vaccinology even further, leveraging not only the speed at which the technology can be designed and tested in response to infectious disease outbreaks but also the potential to create more durable and accessible mRNA vaccines for greater global protection when faced with a deadly disease threat."

CEPI's investment aligns with its broader program to advance RNA vaccine platform technologies, aiming for substantial improvements over existing mRNA platforms. The goal, supported by G7 and G20 leaders, includes compressing vaccine development timelines to 100 days as part of the 100 Days Mission.

"This effort, led by our innovative scientists Drs. John Cooke, Dan Kiss, Jimmy Gollihar, Kristopher Brannan and Francesca Taraballi, together with our colleagues at University of Texas Medical Branch, shows that Houston Methodist is leading medicine by generating fundamental scientific insights that have transformational effects on human health," said Dr. Dirk Sostman, president and CEO of the Houston Methodist Academic Institute.

Both CEPI and Houston Methodist affirm their commitment to equitable access, ensuring that the outcomes of this program are accessible to populations at risk. Project results and data will be published open access for the benefit of the global scientific community, reflecting the organizations' dedication to global health and accessibility.

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