Gene Therapy for ADA-SCID Using an Improved Lentiviral Vector (Ivlv-ADA)

This is a Phase I/II trial of in vivo lentiviral gene therapy for treating adenosine deaminase severe combined immunodeficiency (ADA-SCID) using a self-inactivating lentiviral vector (LV) ivlv-ADA to functionally correct the genetic defect. The primary objectives are to evaluate the safety and efficacy of the direct intravenous (iv) LV gene therapy protocol.

Inclusion Criteria: * Diagnosis of classical ADA-SCID based on: * A proven defective adenosine deaminase (ADA) gene as defined by direct sequencing of patient DNA. * T-cell immune deficiency defined as one or more of the following: CD3+ autologous T cells \< 300/ul, or less than 50% of normal value for in vitro mitogen stimulation, or absent proliferation in vitro to antigens. * With severe infections, including but not limited to: pneumonitis; protracted diarrhea requiring total parenteral nutrition; infection with herpes viruses or adenovirus or fungus; disseminated BCG infection. * No cytogenetic abnormalities (medullary karyotype) and no detection of main rearrangements associated with acute leukemia of children. * No prior allogeneic stem cell transplantation. * Life expectancy ≥ 2 months. * Negative for HIV infection. * Written, informed consent obtained prior to any study-specific procedures. Exclusion Criteria: * None