Primary Immunodeficiencies are a large group of inherited diseases, often caused by single gene mutations, that lead to a defective immune system, and that result in the specific impairment of normal immune development and function. Most PIDs are correlated to an increased susceptibility to infections but can also lead to autoimmune diseases and malignancies. Genes involved in the onset of PIDs often need to be tightly regulated. Mis-regulation of their expression has been associated among others, to unwanted lymphoproliferation. Therefore, although providing an interesting solution for some PIDs, untargeted gene replacement therapies are not always suitable for these diseases. This is why Genespire works at designing disease-specific solutions, where the mutated gene is corrected in situ through targeted replacement based on gene editing. Such a strategy allows to correct the defective gene, while maintaining its natural/physiological regulation. Genespire develops this approach in T-cells in the HIGM program, and in hematopoietic stem cells (HSCs) for other PID thanks to an improved gene editing platform developed by SR-Tiget, designed to enhance the engraftment and safety profiles of the gene edited cells.


Targeted Gene Replacement for PIDs