Inflammatory Bowel Diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic inflammation of the gastrointestinal (GI) tract. Currently available medications, namely small molecular drugs and monoclonal antibodies, present poor therapeutic efficacy and pronounced adverse-effects (systemic immunosuppression), which compromises substantially the quality of life for patients.

 Despite medication, disease progression causes severe complications in the majority of patients, necessitating intestinal resection surgery and emphasizing the urgent need for novel therapeutic interventions. The objective of RELIABLE is to facilitate the utilization of RNA therapeutics targeting the root cause of chronic inflammation, aiming to restore the imbalanced inflammatory state of the intestine. This involves decreasing the local expression of pro-inflammatory cytokines, as the emerging therapeutic target IL-23, and enhancing the expression of anti-inflammatory cytokines as IL-10, under expressed in IBD. To enable the use of RNA therapeutics in the gut, the consortium will develop RNA lipid nanoparticles (LNPs) with improved stability to enable incorporation into established hydrogel systems for oral delivery and local drug release to inflamed areas of the intestine. Upon optimization of systems with the best therapeutic efficacy in vivo, we will additionally establish the certified production of lead hydrogels loaded with RNA-LNPs.

 In summary, the consortium leverages the renowned expertise of the French IBD referral center (HCL) along with specialized knowledge in the development and certified production of RNA LNPs (ULEI, Curapath), hydrogel-based oral delivery technologies (UCBL), and gut immuno- and nano-toxicology (UNIPR). RELIABLE will lay the foundation for oral delivery of RNA LNPs to inflamed gut tissues, unlocking the vast potential of RNA therapeutics for immune modulation in the gastrointestinal tract.