A7 Development of stem cell gene therapies for patients with PID and colitis


PRINCIPAL INVESTIGATOR
AND CO-INVESTIGATORS
OF THE SUBPROJECT
Prof. Klein

Christoph Klein

Christoph Klein, Prof. Dr. med. Dr. sci.
Dr. von Haunersches Kinderspital
Lindwurmstr. 4
D-80337 München
Phone.: +49 89 4400-57700
Fax.: +49 89 4400-57702
E-Mail: christoph.klein@med.uni-muenchen.de


TITLE OF SUBPROJECT

Development of stem cell gene therapies for patients with PID and colitis


CONDITION/TOPIC

Primary immunodeficiency disorders, innate immunity, intestinal immunity, colitis, gene therapy


OBJECTIVE(S)

  1. To develop and characterize novel vectors for hematopoietic stem cell and intestinal epithelial cell gene therapy for defined variants of PID associated with colitis
  2. To comparatively assess toxicity and efficacy of SIN vectors in mouse model systems and the in vitro immortalization assay
  3. To test feasibility and efficacy of intestinal epithelial stem cell gene therapy in a murine Casp8-deficient model system

SUMMARY

Primary immunodeficiency disorders may present as early onset colitis. Based on our previous discovery of causative mutations in IL10 receptor genes, our work on pathomechanisms and our experience in clinical stem cell-based gene therapy, we here propose to set the foundation for novel cures for this group of patients by developing hematopoietic stem cell gene therapy for IL-10R deficiency. We plan to complement the genetic defect by novel SIN retroviral vectors in the hematopoietic system and to design intestinal stem cell therapies in murine models. To this end, intestinal organoid bodies from Casp8-deficient mice will be generated and corrected. Thus, our studies will contribute to the development of innovative therapeutic strategies for children with immunodeficiency disorders and may also have therapeutic implications for patients with more common variants of inflammatory bowel diseases.