@article {1658664,
	title = {Ancestral library identifies conserved reprogrammable liver motif on AAV capsid},
	journal = {Cell Rep Med},
	volume = {3},
	number = {11},
	year = {2022},
	month = {2022 Nov 15},
	pages = {100803},
	abstract = {Gene therapy is emerging as a modality in 21st-century medicine. Adeno-associated viral (AAV) gene transfer is a leading technology to achieve efficient and durable expression of a therapeutic transgene. However, the structural complexity of the capsid has constrained efforts to engineer the particle toward improved clinical safety and efficacy. Here, we generate a curated library of barcoded AAVs with mutations across a variety of functionally relevant motifs. We then screen this library in\&nbsp;vitro and in\&nbsp;vivo in mice and nonhuman primates, enabling a broad, multiparametric assessment of every vector within the library. Among the results, we note a single residue that modulates liver transduction across all interrogated models while preserving transduction in heart and skeletal muscles. Moreover, we find that this mutation can be grafted into AAV9 and leads to profound liver detargeting while retaining muscle transduction-a finding potentially relevant to preventing hepatoxicities seen in clinical studies.},
	keywords = {Animals, Capsid, Capsid Proteins, Dependovirus, Genetic Vectors, Liver, Mice},
	issn = {2666-3791},
	doi = {10.1016/j.xcrm.2022.100803},
	author = {Zinn, Eric and Unzu, Carmen and Schmit, Pauline F and Turunen, Heikki T and Zabaleta, Nerea and Sanmiguel, Julio and Fieldsend, Allegra and Bhatt, Urja and Diop, Cheikh and Merkel, Erin and Gurrala, Rakesh and Peacker, Bryan and Rios, Christopher and Messemer, Kathleen and Santos, Jennifer and Estelien, Reynette and Andres-Mateos, Eva and Wagers, Amy J and Tipper, Christopher and Vandenberghe, Luk H}
}
