A designer AAV variant permits efficient retrograde access to projection neurons

By D. G. Tervo, B. Hwang, Sarada Viswanathan, T. Gaj, Maria Lavzin, K. Ritola, S. Lindo, Susan C. Michael, Elena Kuleshova, David S. Ojala and 8 more. Neuron, 2016

1,131 citations recorded by the source corpus.

Summary 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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bb5f0f85f84a5f084c318e5551dacc6eac02b7dd

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Citations in the corpus

A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2020, neutral): “We injected rAAV2-retro-EF1adTomato (Tervo et al., 2016) into Gnb4-IRES2-CreERT2;Ai140 and Cux2-CreERT2;Ai140 (Daigle et al.”
A Neural Circuit for Gut-Induced Reward. (2018, neutral): “We first transfected the stomach and duodenum of wild-type mice with a retrogradely transported, adeno-associated virus carrying a Cre-EBFP construct (AAVrg-pmSyn1-EBFP-Cre, Tervo et al., 2016).”
In vivo imaging of dentate gyrus mossy cells in behaving mice (2017, methodology): “Therefore, we used a retrograde variant of recombinant adeno-associated virus (rAAV2-retro) (Tervo et al., 2016) expressing Cre-recombinase injected into the contralateral DG, in combination with a Cre-dependent rAAV expressing GCaMP6f injected ipsilaterally into the hilar imaging site, to label con”