@article{bc6fad4c2d2e47d7868f95fb16ec2706,
title = "A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons",
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.",
author = "Tervo, {D. Gowanlock R.} and Hwang, {Bum Yeol} and Sarada Viswanathan and Thomas Gaj and Maria Lavzin and Ritola, {Kimberly D.} and Sarah Lindo and Susan Michael and Elena Kuleshova and David Ojala and Huang, {Cheng Chiu} and Gerfen, {Charles R.} and Jackie Schiller and Dudman, {Joshua T.} and Hantman, {Adam W.} and Looger, {Loren L.} and Schaffer, {David V.} and Karpova, {Alla Y.}",
note = "Funding Information: We are indebted to K. Svoboda for suggesting the use of Rosa26 -STOP-Lox-H2B-EGFP mice. We thank H. Adesnik for providing the Rbp4_KL 100 Cre × tdTomato mouse line, J. Brousseau for invaluable assistance with the pilot experiments, M. Proskurin for help with the rat experiments, and J. Santiago-Ortiz for help with the CRISPR/Cas9 experiments. We are grateful to the members of the J.T.D., A.W.H., Jessell, Ji, A.Y.K., Petreanu, Sabatini, Spruston, Svoboda, and Zuker labs for beta testing rAAV2-retro and contributing their findings to the knowledge base summarized in Table S2 . T. Jessell, N. Spruston, and K. Svoboda offered useful discussions and comments on the manuscript. D.V.S. is supported by NIH R01EY022975 and T.G. by F32GM113446. This work was supported by the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
month = oct,
day = "19",
doi = "10.1016/j.neuron.2016.09.021",
language = "English (US)",
volume = "92",
pages = "372--382",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}