Report Summary

Pharmacology/Toxicology Study of the EFS-ADA Lentiviral Vector in Mice

Study Summary

Overall Study Design 
This study is designed to provide information about the pharmacology and toxicology of the EFS-ADA lentiviral vector This 
vector is being evaluated for use in a clinical trial of gene therapy for children with adenosine deaminase ADA-deficient 
severe combined immune deficiency SCID The EFS-ADA lentiviral vector will be used for ex vivo gene transduction of 
patients CD34 cells isolated from their bone marrow 
   For this pharmacologytoxicology study bone marrow from B6SJL-Ptprca Pep3bBoy murine donors Ly51 will be 
enriched for lineage-negative cells lin- and transduced with the EFS-ADA vector or controls during ex vivo culture The 
transduced lin- bone marrow cells will then be transplanted by intravenous injection into congenic C57BL6J recipients 
Ly52 after 1050 cGy total body-irradiation TBI After 4 months the mice will be euthanized and primary end-points 
measured Portions of the bone marrow will be used to transplant secondary recipients C57BL6J after 1050 cGy TBI 
and these will be analyzed as above after two months Five mice per group will be treated in each set and a total of 16 sets 
of transplants will be done for a total number of 80 treated animals per treatment group These studies will determine a 
the biodistribution of the EFS-ADA vector provirus in cells descended from the transduced bone marrow and b if the 
EFS-ADA vector leads to toxicity in terms of abnormalities in blood cell numbers serum chemistries reflecting hepatic and 
renal function and any abnormalities in tissues such as inflammation andor leukoproliferation If leukoproliferation is 
observed we will examine DNA extracted from the affected tissues to determine the level of vector provirus the clonality of 
vector integrants and the specific chromosomal vector integration sites These studies will provide pharmacology and 
toxicology data to support evaluation of the EFS-ADA lentiviral vector in a clinical trial of gene transfer for patients with 
ADA-deficient SCID 

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