In Vivo–Directed Evolution of a New Adeno-Associated Virus for Therapeutic Outer Retinal Gene Delivery from the Vitreous

By D. Dalkara, L. Byrne, R. Klimczak, Meike Visel, Lu Yin, W. Merigan, J. Flannery, David V. Schaffer. Science Translational Medicine, 2013

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A designer AAV variant permits efficient retrograde access to projection neurons (2016, background): “However, the resulting increase in vector spread alone cannot explain the efficacy of retrograde transport, as other inserted 7-mer sequences disrupt heparin binding similarly but do not affect retrograde transport (Dalkara et al., 2013).”
Deep diversification of an AAV capsid protein by machine learning (2021, background): “Previous engineering strategies, such as error-prone mutagenesis 11 , random shuffling between AAV serotypes to create chimeric capsids 10 , and random mutation at structurally guided positions 27 have shown limited success in overcoming antibody neutralization, because the resultant sequences…”