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Directed evolution of AAV accounting for long-term and enhanced transduction of cardiovascular endothelial cells

Mol Ther Methods Clin Dev. 2021-06; 
Y B Liu, B C Xu, Y T Chen, X Yuan, J Y Liu, T Liu, G Z Du, W Jiang, Y Yang, Y Zhu, L J Chen, B S Ding, Y Q Wei, L Yang
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摘要

Cardiac endothelial cells (ECs) are important targets for cardiovascular gene therapy. However, the approach of stably transducing ECs using different vectors, including adeno-associated virus (AAV), remains unexamined. Regarding this unmet need, two AAV libraries from DNA shuffling and random peptide display were simultaneously screened in a transgenic mouse model. Cardiac ECs were isolated by cell sorting for salvage of EC-targeting AAV. Two AAV variants, i.e., EC71 and EC73, enriched in cardiac EC, were further characterized for their tissue tropism. Both of them demonstrated remarkably enhanced transduction of cardiac ECs and reduced infection of liver ECs in comparison to natural AAVs after intravenous in... More

关键词

adeno-associated virus, cardiac endothelial cells, cardiovascular gene therapy, directed evolution, transduction