Background: Trafficking pathways underlying retrograde transduction of neurons with lentiviral vectors carrying the rabies G glycoprotein are uncharted, and barriers to high transduction efficiencies are undefined. Results: Vectors are internalized through cognate receptors and transported to the soma by fast axonal transport in pH-neutral endosomes. Conclusion:The major barrier to axonal transduction is postaxonal transport. Significance: Enhancing endosomal escape will be a novel area for improvement of gene therapy vector transduction efficiency.

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