Gene therapy of primary T cell immunodeficiencies

- This review describes the status of gene therapy of disorders of the immune system.
- Proof of principle of efficacy has been provided for 2 forms of SCID.
- Genotoxicity related to the vector was observed in the first trials.
- Usage of self-inactivated vectors may overcome this problem.

Gene therapy of severe combined immunodeficiencies has been proven to be effective to provide sustained correction of the T cell immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (γc deficiency) and adenosine deaminase deficiency. Occurrence of gene toxicity generated by integration of first generation retroviral vectors, as observed in the SCID-X1 trials has led to replace these vectors by self inactivated (SIN) retro(or lenti) viruses that may provide equivalent efficacy with a better safety profile. Results of ongoing clinical studies in SCID as well as in other primary immunodeficiencies, such as the Wiskott Aldrich syndrome, will be thus very informative.