A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons

Tervo DG, etc
Neuron, 2016


Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential. To address this need, we applied in vivo directed evolution to engineer potent retrograde functionality into the capsid of adeno-associated virus (AAV), a vector that has shown promise in neuroscience research and the clinic. A newly evolved variant, rAAV2-retro, permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde tracers and enables sufficient sensor/effector expression for functional circuit interrogation and in vivo genome editing in targeted neuronal populations.

The AAVe(retro) virus used in this paper was produced by Vector Biolabs.

Read more »

Journal
Neuron
Year
2016
Page
doi: 10.1016/j.neuron.2016.09.021
Institute
Howard Hughes Medical Institute