Harnessing Ancient Viral Biology to Advance New Age RNA Therapies
October 22, 2019 | | 2 Minute Read
RNA, once viewed as passive carriers of genetic information, is arguably the most versatile and potent regulator of biological processes and diseases. Developing RNA as drug agents for the treatment of complex diseases such as cancer and genetic disorders is therefore, an exciting area of research. While RNA therapeutics has the potential to change the trajectory of a disease and its treatment, it is not without its challenges. Superior efficacy with RNA drugs often requires high and frequent dosing, increasing the risk of drug related toxicities in the patient. An ancient class of small virus, called alphavirus, have a unique property or phenomenon that can help address this limitation. This virus family have within them just a single piece of a small RNA. Despite its simple and primitive architecture, an alphavirus can efficiently infect, survive and grow in cells. This is because, these viruses have smart in-built mechanisms that allows the single RNA to self-amplify. Once the RNA is in the infected cell, it self-amplifies, such that 1 copy of the delivered RNA ends up making several 1000s or greater copies of itself in-turn translates into proteins that is required for its survival.
Chimeron Bio has harnessed this property and developed a self-amplifying synthetic nanoparticle, which we call ChaESAR™. Each ChaESAR™ particle contains a therapeutic RNA inside it. As shown in the cartoon, once the ChaESAR™ particle delivers the RNA into the cell, the RNA self-amplifies and produces multiple copies of itself. Therefore, unlike traditional technologies which requires delivery of multiple RNA copies for a detectable protein response, the ChaESAR™ technology can achieve comparable or even superior protein response with just 1 copy of the delivered therapeutic RNA. This self-amplification property provides a broader dynamic window, which we expect to translate in the clinic as an RNA drug with low dose efficacy and a favorable toxicity profile. Our belief is that patients on ChaESAR™ drugs will not need frequent dosing to achieve relief from diseases.
We have further designed ChaESAR™ to carry more than one RNA species. A single ChaESAR™ formulation can target multiple proteins and hence, modulate multiple dysregulated pathways or functions for an effective cure. Finally, the ChaESAR™ RNA molecule is wrapped in a special organic coat which not only stabilizes the RNA as it enters the blood stream, but which can be easily reengineered for tissue targeting. We at Chimeron Bio believe that ChaESAR™ technology can have a broad impact across therapeutic areas and we are currently investigating ChaESAR™ drugs in cancer, rare and genetic disorders. Find out more about our technology at www.chimeron.com