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Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency

Adeno-associated viruses (AAVs) have become safe and effective tools for therapeutic in vivo gene drug delivery. Among many AAV serotypes, AAV2 is the most well-characterized. Although many studies have been carried out on the engineering of the capsid VR-VIII region, few attempts have been made in...

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Autores principales: Han, Zengpeng, Luo, Nengsong, Wang, Fei, Cai, Yuxiang, Yang, Xin, Feng, Weiwei, Zhu, Zhenxiang, Wang, Jie, Wu, Yang, Ye, Chaohui, Lin, Kunzhang, Xu, Fuqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143561/
https://www.ncbi.nlm.nih.gov/pubmed/37112829
http://dx.doi.org/10.3390/v15040848
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author Han, Zengpeng
Luo, Nengsong
Wang, Fei
Cai, Yuxiang
Yang, Xin
Feng, Weiwei
Zhu, Zhenxiang
Wang, Jie
Wu, Yang
Ye, Chaohui
Lin, Kunzhang
Xu, Fuqiang
author_facet Han, Zengpeng
Luo, Nengsong
Wang, Fei
Cai, Yuxiang
Yang, Xin
Feng, Weiwei
Zhu, Zhenxiang
Wang, Jie
Wu, Yang
Ye, Chaohui
Lin, Kunzhang
Xu, Fuqiang
author_sort Han, Zengpeng
collection PubMed
description Adeno-associated viruses (AAVs) have become safe and effective tools for therapeutic in vivo gene drug delivery. Among many AAV serotypes, AAV2 is the most well-characterized. Although many studies have been carried out on the engineering of the capsid VR-VIII region, few attempts have been made in the VR-IV region. Here, we targeted amino acid positions 442–469 of the VR-IV region and established an engineering paradigm of computer-aided directed evolution, based on training samples from previous datasets, to obtain a viral vector library with high diversity (~95,089). We further examined two variants selected from the library. The transduction efficiency of these two novel AAV variants, AAV2.A1 and AAV2.A2, in the central nervous system was 10–15 times higher than that of AAV2. This finding provides new vehicles for delivering gene drugs to the brain.
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spelling pubmed-101435612023-04-29 Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency Han, Zengpeng Luo, Nengsong Wang, Fei Cai, Yuxiang Yang, Xin Feng, Weiwei Zhu, Zhenxiang Wang, Jie Wu, Yang Ye, Chaohui Lin, Kunzhang Xu, Fuqiang Viruses Communication Adeno-associated viruses (AAVs) have become safe and effective tools for therapeutic in vivo gene drug delivery. Among many AAV serotypes, AAV2 is the most well-characterized. Although many studies have been carried out on the engineering of the capsid VR-VIII region, few attempts have been made in the VR-IV region. Here, we targeted amino acid positions 442–469 of the VR-IV region and established an engineering paradigm of computer-aided directed evolution, based on training samples from previous datasets, to obtain a viral vector library with high diversity (~95,089). We further examined two variants selected from the library. The transduction efficiency of these two novel AAV variants, AAV2.A1 and AAV2.A2, in the central nervous system was 10–15 times higher than that of AAV2. This finding provides new vehicles for delivering gene drugs to the brain. MDPI 2023-03-26 /pmc/articles/PMC10143561/ /pubmed/37112829 http://dx.doi.org/10.3390/v15040848 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Han, Zengpeng
Luo, Nengsong
Wang, Fei
Cai, Yuxiang
Yang, Xin
Feng, Weiwei
Zhu, Zhenxiang
Wang, Jie
Wu, Yang
Ye, Chaohui
Lin, Kunzhang
Xu, Fuqiang
Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title_full Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title_fullStr Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title_full_unstemmed Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title_short Computer-Aided Directed Evolution Generates Novel AAV Variants with High Transduction Efficiency
title_sort computer-aided directed evolution generates novel aav variants with high transduction efficiency
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143561/
https://www.ncbi.nlm.nih.gov/pubmed/37112829
http://dx.doi.org/10.3390/v15040848
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