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- W2565894805 abstract "Intrathecal (IT) delivery of adeno-associated viral (AAV) vector is currently used for the treatment of neurodegenerative disorders. To date, there is no standardized method to deliver the vector into the cerebrospinal fluid (CSF). Several parameters could impact the transduction efficacy among them the dose, the AAV serotype or the volume of injection. In this study, we analyzed the impact of large vector volume administered in the lumbar CSF on the vector biodistribution. Cynomolgus monkeys were injected with a serotype 10 AAV vector (AAVrh10) a serotype known to transduce efficiently the CNS via a pre-implanted catheter. The catheter was inserted after a hemilaminectomy at approximately the L5 vertebra, and advanced intrathecally with the tip located near the thoracolumbar junction. The rAAVrh10 (5.0 ml) was administered as two 2.5 ml infusions (the second infusion was approximately six hours after initiation of the first infusion). The infusion rate was 7.5 ml/hr over approximately 20 minutes. For the duration of both infusion, the NHPs were restrained in a prone position with the restraint table tilted approximately 30 degrees head-down. The vector biodistribution was analyzed by digital PCR and the results demonstrate that viral genomes are detected along the entire length of the spinal cord but also in substantial levels in peripheral organs. Due to viral genomes detected in lymphoid organs, we are currently analyzing the immune response to AAV capsid. These results are important for assessing the safety of IT delivery in large animal models before translation to human clinical trials." @default.
- W2565894805 created "2017-01-06" @default.
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- W2565894805 date "2016-05-01" @default.
- W2565894805 modified "2023-10-03" @default.
- W2565894805 title "90. Vector Biodistribution After Recombinant AAVrh10 Intrathecal Delivery in Non-Human Primates" @default.
- W2565894805 doi "https://doi.org/10.1016/s1525-0016(16)32899-4" @default.
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