Leading the RNA Revolution

With funding from CEPI and in collaboration with groups at The University of Texas Medical Branch (UTMB) and Baylor College of Medicine (BCM), Cooke will lead the Center’s effort to refine the novel circular RNA vaccine platform (circRNA) developed in the Kiss Lab; to incorporate antigen designs generated by the Gollihar Lab; to optimize protocols for scaling up production in the RNACore; and to test the efficacy of the vaccines in pre-clinical models of the UTMB group. This platform was built upon the groups’ extensive experience and expertise in manufacturing research quality and clinical grade RNA; antigen selection and protein engineering; the design, generation, and packaging of RNA into lipid nanoparticles; virology and immunology; and vaccine evaluations. The funded project is expected to demonstrate that their circRNA platform can be used to quickly generate vaccines with characteristics needed to effectively prevent an outbreak from turning into a pandemic, such as multivalency, improved balance of immunogenicity/reactogenicity, thermostability and enhanced response time — all with just a single dose. Key Houston Methodist researchers on the project include Daniel Kiss, PhD, Assistant Professor of Cardiovascular Sciences, Jimmy Gollihar, PhD, Professor of Pathology and Genomic Medicine, Kristopher Brannan PhD, Assistant Professor in the Department of Cardiovascular Sciences and the Center for RNA Therapeutics and Francesca Taraballi PhD, Assistant Professor of Orthopedic Surgery. Kiss, an RNA molecular biology expert, developed the circular RNA technology. Gollihar, a protein engineer, developed the high-throughput method for finding antigens most likely to result in strong vaccines. Brannan’s STAMP technology to assess RNA binding proteins will guide RNA design and Taraballi, a nanomedicine expert, will lead circRNA encapsulation.

Collaborators at UTMB include Scott Weaver, PhD. Weaver is director, Institute for Human Infections & Immunity, scientific director, Galveston National Laboratory, Chair, Department of Microbiology & Immunology and professor, Microbiology & Immunology and Pathology whose group is internationally recognized for their expertise in virology and vaccine development and testing. The project is pre-clinical, but the group intends to obtain data needed to design a clinical trial and enable an Investigational New Drug submission to test the cGMP-manufactured circRNA vaccine. Specifically, they will evaluate circRNA vaccine safety; toxicity and reactogenicity; efficacy; and dose range in a pre-clinical model of chikungunya, a mosquito-borne virus causing a spectrum of disease, from self-limited febrile illness to permanent severe disability, congenital anomalies and early death. In the future, a Phase 1 clinical trial would evaluate the safety, reactogenicity and immunogenicity of ascending dosages of the vaccines in young healthy adults with safety as the primary endpoint.

Cooke’s team was recently awarded a subcontract from BARDA for a project led by Nature’s Toolbox (NTx) designed to complete development of, and demonstrate, a fully deployable manufacturing unit for production of cGMP RNA vaccines. The result will be a novel RNA manufacturing platform that can be used not only for pandemic response, but a more efficient response to local medical needs.

As a subcontractor on the contract, Cooke’s team brings proven capabilities in cGMP manufacturing and proof-of-concept deployment assessment in a hospital setting. “The idea is you have a box, you put the reagents in at one end and you get your vaccine out at the other. So, rather than having to ship the vaccine and use cold chain to get it to a low-income country suffering an outbreak, or a theater of war where biological weapons are being used, BARDA could ship the manufacturing unit and the RNA drug could be made on-site,” Cooke said. He added, “This technology is also going to accelerate the democratization of RNA therapeutics because it will be possible for other hospitals to do what we're doing. The “box” will facilitate hospital-based RNA therapeutics programs for personalized RNA therapy without the need for expensive clean rooms. Our institute went to a lot of expense to generate these clean rooms and it costs a lot to maintain and staff them, but other hospitals won’t need to do that if they have these deployable manufacturing units.” Combined, these projects further strengthen Houston Methodist’s position on the front lines of emerging infectious disease research and will significantly advance pandemic preparedness and development of countermeasures to a myriad of global public health threats.