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In Vivo Direct Reprogramming of Resident Glial Cells into Interneurons by Intracerebral Injection of Viral Vectors
Published on: June 17, 2019
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Engineered viral vectors for functional interrogation, deconvolution, and manipulation of neural circuits
Sabrina Sun1, David V Schaffer2
1Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA.
Current Opinion in Neurobiology
|April 4, 2018
Summary
Adeno-associated viral (AAV) vectors offer a safer, persistent alternative to traditional viral tracers for mapping brain circuits. Engineered AAV variants enhance neuronal targeting and genetic tool delivery for detailed circuit analysis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Traditional replication-competent viral tracers enable immediate synaptic partner identification but have excessive virulence.
- This virulence limits long-term studies of cellular function and genetic perturbation.
- Adeno-associated viral (AAV) vectors are being explored as a safer alternative for persistent gene expression.
Purpose of the Study:
- To adapt AAV vectors for sparse neuronal labeling and physiological studies.
- To leverage engineered AAV variants for enhanced neuronal targeting and retrograde trafficking.
- To utilize potent AAV vectors for characterizing single neuron identity, connectivity, and activity modulation.
Main Methods:
- Optimization of traditional viral tracers.
- Development and application of novel adeno-associated viral (AAV) vector variants.
- Engineering strategies for enhanced target specificity, transduction, and retrograde transport in the CNS.
- Delivery of functional genetic tools for modulating neuronal activity.
Main Results:
- AAV vectors provide a safe and persistent method for gene expression.
- Engineered AAV variants show improved target specificity and transduction efficiency.
- Enhanced retrograde trafficking capabilities in novel AAVs.
- Successful characterization and modulation of single neurons within complex networks.
Conclusions:
- AAV vectors are a promising alternative to conventional viral tracers for neuroscience research.
- Engineered AAVs offer enhanced capabilities for dissecting complex brain circuits.
- These vectors facilitate detailed analysis of neuronal identity, connectivity, and function.
