Format

Send to

Choose Destination
Neuron. 2016 Oct 19;92(2):372-382. doi: 10.1016/j.neuron.2016.09.021. Epub 2016 Oct 6.

A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons.

Author information

1
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
2
Department of Chemical Engineering and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
3
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Department of Physiology, Technion Medical School, Bat-Galim, Haifa 3525433, Israel.
4
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, Moscow 117485, Russia.
5
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA; Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA.
6
Department of Chemical Engineering and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA. Electronic address: schaffer@berkeley.edu.
7
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: alla@janelia.hhmi.org.

Abstract

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. VIDEO ABSTRACT.

PMID:
27720486
PMCID:
PMC5872824
DOI:
10.1016/j.neuron.2016.09.021
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center