Résumé :
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We developed in the nonhuman primate (NHP) a drug-free regional intravenous (RI) delivery protocol of recombinant adeno-associated virus (rAAV) 1 and 8 to an entire limb and compared it with the intramuscular (IM) delivery of the same dose of vector. We show that RI delivery of both serotypes was remarkably well tolerated with no adverse side effects. After IM, muscle transduction was restricted to the site of injection with a high number of vector copies per cell for rAAV1, whereas RI delivery resulted in lower vector copy per cell but detectable in the vast majority of muscles of the injected limb. The amounts of circulating infectious rAAV were similar for both serotypes and modes of delivery. At autopsy, up to 34 months post vector administration, similar biodistribution patterns were found for both vectors and modes of delivery, with numerous organs positive for vector sequence by PCR and Southernblot. Altogether, we demonstrated that RI is a simple and efficient transduction protocol in NHP, resulting in higher expression of the transgene with a lower number of vector genomes per cell. However, regardless of the mode of delivery, concerns were raised by vector sequence detected at distant sites.
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