Development of advanced technologies for gene therapy manufacture

Primary Immunodeficiency disorders are rare genetic defects of blood cells that affect children and often lead to early death. Up to a few years ago the only proven cure for those type of disorders was haematopoietic stem cell (HSC) transplantation, although complicated by the need to identify a suitable donor and severe side effects. Recently developed technologies allow correction of genetic defects in HSCs isolated from peripheral blood or bone marrow by manipulating them ex-vivo and re-infusing them back into the patient. Once back in the patient, the corrected cells "home" to the bone marrow where they produce healthy immune cells. One way of correcting genetic defects is by adding a healthy copy of the defective gene to HSCs using a virus vector. The infected HSCs go on to reconstitute the hematopoietic system with blood cells carrying the correct gene. However, a major challenge is to correct a sufficient number of HSCs without altering their ability to give rise to all blood cells for during the lifetime of the patient. Plasticell has developed a clinically compliant process to expand cord blood cells ex vivo and now plans to use its HSC expansion protocol to improve the efficiency of gene therapy. The overall aim of this project is to progress with the clinical application of the Plasticell formulation that stimulates expansion of true hematopoietic stem cells in vitro and to provide a high number of corrected stem cells after gene therapy. We will also use Plasticell's combinatorial screening technology, CombiCult, to increase the efficiency of viral gene delivery in HSC. Both technologies will be used to develop a new clinical protocol for viral gene therapy that would increase the efficacy and lower the overall cost of the gene therapy procedure.