TOLERANCE INDUCED BY INTRATHYMIC INJECTION OF RECOMBINANT ADENOVIRUS IN THE NEONATE

Major limitations of first-generation recombinant adenoviral vectors are the inflammatory reaction they provoke and the transient expression of transgenes they introduce into cells. These phenomena are mainly due to a cellular immune response directed against the virus. We have tried to tolerize rats to the adenovirus by injecting this vector intrathymically at birth. By this approach, it was possible to prolong transgene expression for more than 2 months after an intramyocardial injection in adults whereas this expression lasted less than 21 days after injection in nontolerized animals. Intrathymic injection of first-generation adenovirus could therefore constitute a way to evaluate the adenovirus-mediated gene transfer efficiency in animal models of human genetic diseases, avoiding side effects related to the immune response.