We have designed siRNA sequences targeting human JAK1, human JAK3, murine JAK1 and murine JAK3 and validated their specificity in in vitro models. The selected sequences lead to a very high downregulation efficiency without observed neither off-target effects nor unwanted Toll-like receptors activation up to now. The phenotypic outcomes of the JAK1 knockdown have been properly investigated in human cells, as compared to chemical inhibitors. Up to now, we do not observe significant impact on proliferation or cell death rates after JAK1 downregulation by the mean of siJAK1. . In parallel, nanostructured lipid carriers (NLCs) have been designed and prepared in order to carry siRNA biomolecules. These particles presented very high colloidal stability and a good safety profile. We have validated that they were compatible with preparation processes of formulations for human administration (rectal and/or oral dosage forms), like spray drying.We have demonstrated that the NLCs can diffuse across the mucosal barrier and can even reach the immune cells from the lamina propria after rectal administration in animal models.. We encountered some instability issue of the nanocomplexes (siRNA loaded NLCs) in colonic media, that we could overcome during the period 2, by promoting the interaction of siRNA to the particles through its chemical modification.. Draft of the clinical development plan has been drawn and the main regulatory requirements have been identified and shared with the consortium, but these tasks have been hampered by the technical issue of nanocomplexe instability, which has delayed the preclinical validation.All our efforts are done to achieve the solid proof of concept at the preclinical level for the last period, which is needed to fulfil the clinical development plan.