Feasibility of Targeted Delivery of AAV5-GFP into the Cerebellum of Nonhuman Primates Following a Single Convection-Enhanced Delivery Infusion
| Autor: | Marc Gonzalez, Granger G.C. Hwa, Diane E. Stockinger, Summer Copeland, Emily Lambert, Mira J. Cukrov, Abigail Green, Jeremy M. Yeung, Rachel Lortz, Ernesto A. Salegio |
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| Rok vydání: | 2021 |
| Předmět: |
Volume of distribution
Primates Pathology medicine.medical_specialty Cerebellum Transgene Genetic Vectors Green Fluorescent Proteins Antibody titer Biology Dependovirus Convection Green fluorescent protein Transduction (genetics) medicine.anatomical_structure Genetics medicine Molecular Medicine Distribution (pharmacology) Animals Feasibility Studies Molecular Biology Tropism |
| Zdroj: | Human gene therapy. 33(1-2) |
| ISSN: | 1557-7422 |
| Popis: | In this study, we built upon our previous work to demonstrate the distribution and transport of AAV5-GFP following a single CED infusion into the nonhuman primate cerebellum, with no untoward side effects noted. Dosing under MRI guidance revealed a 6-fold larger volume of distribution compared to the volume of infusion, with no evidence of reflux underscoring the convective properties of the cerebellum and step design of the cannula. Post-mortem tissue analysis, four weeks post AAV delivery revealed the robust presence of the transgene in situ, with GFP detection in secondary regions not directly targeted by the infusion, denoting distal transport of the vector. Irrespective of tropism, a 2-fold larger area of transgene expression was found and was corroborated against the presence of contrast on T1-weighted images. Different levels of transduction were detected between animals, which was negatively correlated with the level of antibody titer against the GFP construct, whereby, the higher the antibody titer, the lower the level of transgene expression. These findings support the use of the posterior fossa as a potential target site for the direct delivery of gene-based therapeutics for cerebellar diseases. |
| Databáze: | OpenAIRE |
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