Myeloid-targeted gene therapy for immunological, metabolic and neurological diseases

We are developing novel myelospecific gene therapy for phagocyte-mediated diseases that are due to loss-of-function mutations. Current preclinical development focuses on primary phagocyte immunodeficiencies such as chronic granulomatous diseases, metabolic (lysosomal storage disorders) and neurological diseases (genetic early-onset dementias) in which phagocytes play a major role.

We develop gene therapies based on lentiviral gene transfer as well as gene editing approaches to correct or add a sequence at the desired position. The basic principle of future therapy with these strategies consists of genetic modification of autologous stem cells for a once-in-a-lifetime treatment and potential cure. Addition of a healthy gene copy into hematopoietic stem cells, with expression of the therapeutic protein only at the phagocyte level is an important safety feature of our therapies.

As corrected phagocytes can travel to the brain from the bone marrow, where they are produced from hematopoietic stem cells, and then cross the intact blood-brain-barrier, we plan to exploit this feature to provide corrected phagocyte/microglia to the brain to address genetic neurometabolic and neurodegenerative diseases.

PhD students
Martina Nubiè

Postdoctoral Researchers
Dr. Kah Mun Siow