Bacterial-Derived Therapeutics based on CircRNAs (BacTheRNA)

ended

RNA therapeutics are a rapidly growing field of research, thanks to their enormous potential. However, production costs and delivery systems represents the major issues for their widespread use in clinics. BacTheRNA aims at overcoming these issues by developing novel circular RNA (circRNA)-based therapeutics using recombinant food-grade bacteria. CircRNAs are advantageous over their linear counterpart, for their stability due to their intrinsic resistance to nucleases (which cannot cut circular molecules without free ends). Their production costs are thus lower, as they do not need chemical or enzymatic modifications. Moreover, production in bacteria is simpler than chemical synthesis and it is scalable, with further reduced production costs. CircRNAs will be either purified as naked molecules or will be directly secreted by the bacteria in extracellular vesicles (EVs) embedding targeting moieties. Importantly, non-immunogenic circRNAs can be designed. Intriguingly, BacTheRNA will demonstrate that it is possible to include targeting moieties directly through programming of circRNAs natural packaging, i.e. by expressing appropriate surface ligands on recombinant EVs. Finally, the potential to reach increased efficiency thanks to the possibility of amplification through rolling circle mechanisms is yet another innovative aspect of these next-generation RNA therapeutics. As a proof-of-concept, circRNAs produced in BacTheRNA will be applied to Type 2 Diabetes Mellitus (T2DM) as a model target disease. Nevertheless, BacTheRNA will demonstrate a general strategy, which can potentially be exploited in several other pathologies that may benefit of RNA therapeutics approaches.