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Convection Enhanced Delivery of Optogenetic Adeno-associated Viral Vector to the Cortex of Rhesus Macaque Under Guidance of Online MRI Images
Published on: May 23, 2019
Adenovirus-mediated transgene expression in nonhuman primate brain
M C Bohn1, D L Choi-Lundberg, B L Davidson
1Department of Pediatrics, Children's Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL 60614, USA. m-bohn@nwu.edu
Human Gene Therapy
|May 26, 1999
Summary
Finding the right adeno-associated virus (AAV) titer is key for sustained transgene expression in primate brains. Too high a viral vector dose triggers immune responses, limiting expression, while lower doses show better persistence.
Area of Science:
- Neuroscience
- Gene Therapy
- Virology
Background:
- Adenoviral vectors are used for gene delivery to the brain.
- Understanding optimal vector titers is crucial for effective gene therapy in primates.
Purpose of the Study:
- To investigate transgene expression duration and host response in primate brains using an E1E3-deleted adenovirus vector.
- To determine the optimal vector titer for persistent gene expression in the St. Kitts green monkey (Cercopithecus aethiops sabeus).
Main Methods:
- Injection of E1E3-deleted adenovirus vector carrying the beta-galactosidase (beta-Gal) transgene into the caudate nuclei of 18 monkeys.
- Administration of dexamethasone and sacrifice at various time points (1 week to 3 months).
- Quantification of beta-Gal expressing cells and assessment of host immune response via MHC II DR staining.
Main Results:
- Transgene expression was observed in neurons and astrocytes at 1 week post-injection.
- Persistent transgene expression was detected up to 3 months in some cases, with optimal expression at specific titers.
- Higher vector titers led to intense MHC II DR staining, correlating with reduced transgene persistence, suggesting an immune response.
Conclusions:
- An optimal range of vector titers exists for achieving persistent transgene expression in primate brains using E1E3-deleted adenoviruses.
- Elevated vector titers can elicit host immune responses that limit transgene stability.
- These findings have implications for optimizing gene therapy strategies in non-human primates.
