Comparative Analyses of Adeno-Associated Viral Vector Serotypes 1, 2 and 9 in the SOD Mouse Model of Amyotrophic Lateral Sclerosis
Poster Abstract
6–7-week-old G93A SOD mice were given 1x1010 vector genomes of three different self-complimentary (sc) AAV capsid serotypes (AAV1, 2, and 9) all containing an identical CBh-driven GFP reporter expression cassette. Each serotype was delivered via either the intrathecal (IT) or intra cisterna magna (ICM) route of administration (ROA). Transduction by each serotype, via each of the two ROA was compared for the cortex and each of the lumbar, thoracic, and cervical regions of the spinal cord, with percent neuronal tropism calculated in each region. AAV2 was effective at transducing spinal cord neurons but disappointingly ineffective at transducing cortical neurons by either ROA. AAV1 and AAV9 showed similar transduction profiles in both cortex and spinal cord via the IT ROA, with positive cortcial transduction being ~50% neuronal for both serotypes. When delivered via ICM, AAV1 resulted in very targeted expression of cortical layer V neurons with near 100% neurotropism, while AAV9 ICM brains exhibited more diffuse cortical expression, mainly outside of cortical layer V, with ~50% neurotropism. Spinal cord transduction via the ICM ROA was comparable for both AAV1 and AAV9, but with AAV1 exhibiting significantly higher neurotropism. In conclusion AAV1 delivered via the ICM route appears well suited to the targeting of corticospinal motor neurons and lower motor neurons of the spinal cord.
Comparative Analyses of Adeno-Associated Viral Vector Serotypes 1, 2 and 9 in the SOD Mouse Model of Amyotrophic Lateral Sclerosis
6–7-week-old G93A SOD mice were given 1x1010 vector genomes of three different self-complimentary (sc) AAV capsid serotypes (AAV1, 2, and 9) all containing an identical CBh-driven GFP reporter expression cassette. Each serotype was delivered via either the intrathecal (IT) or intra cisterna magna (ICM) route of administration (ROA). Transduction by each serotype, via each of the two ROA was compared for the cortex and each of the lumbar, thoracic, and cervical regions of the spinal cord, with percent neuronal tropism calculated in each region. AAV2 was effective at transducing spinal cord neurons but disappointingly ineffective at transducing cortical neurons by either ROA. AAV1 and AAV9 showed similar transduction profiles in both cortex and spinal cord via the IT ROA, with positive cortcial transduction being ~50% neuronal for both serotypes. When delivered via ICM, AAV1 resulted in very targeted expression of cortical layer V neurons with near 100% neurotropism, while AAV9 ICM brains exhibited more diffuse cortical expression, mainly outside of cortical layer V, with ~50% neurotropism. Spinal cord transduction via the ICM ROA was comparable for both AAV1 and AAV9, but with AAV1 exhibiting significantly higher neurotropism. In conclusion AAV1 delivered via the ICM route appears well suited to the targeting of corticospinal motor neurons and lower motor neurons of the spinal cord.