A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons

D. Gowanlock R. Tervo, Bum Yeol Hwang, Sarada Viswanathan, Thomas Gaj, Maria Lavzin, Kimberly D. Ritola, Sarah Lindo, Susan Michael, Elena Kuleshova, David Ojala, Cheng Chiu Huang, Charles R. Gerfen, Jackie Schiller, Joshua T. Dudman, Adam W. Hantman, Loren L. Looger, David V. Schaffer, Alla Y. Karpova

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)372-382
Number of pages11
JournalNeuron
Volume92
Issue number2
DOIs
StatePublished - Oct 19 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    Tervo, D. G. R., Hwang, B. Y., Viswanathan, S., Gaj, T., Lavzin, M., Ritola, K. D., Lindo, S., Michael, S., Kuleshova, E., Ojala, D., Huang, C. C., Gerfen, C. R., Schiller, J., Dudman, J. T., Hantman, A. W., Looger, L. L., Schaffer, D. V., & Karpova, A. Y. (2016). A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons. Neuron, 92(2), 372-382. https://doi.org/10.1016/j.neuron.2016.09.021