Discovering human cell‐compatible gene therapy virus variants via optimized screening in mouse models

Author:

Dai Moyu123,Yang Ning123,Xu Kai124,Zhang Jingwen15,Li Xueke123,Zhang Ying1234ORCID,Li Wei1234ORCID

Affiliation:

1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences Beijing China

2. Institute for Stem Cell and Regenerative Medicine Chinese Academy of Sciences Beijing China

3. University of Chinese Academy of Sciences Beijing China

4. Beijing Institute for Stem Cell and Regenerative Medicine Chinese Academy of Sciences Beijing China

5. College of Life Science Nankai University Tianjin China

Abstract

AbstractIn gene therapy, intravenous injection of viral vectors reigns as the primary administration route. These vectors include adeno‐associated viruses, adenoviruses, herpes viruses, rhabdoviruses and others. However, these naturally occurring viruses lack inherent tissue or organ tropism for tailored disease treatment. To address this, we devised an optimized process involving directed viral capsid evolution, organ‐specific humanized mouse models and in vitro‐in vivo virus screening. Our approach allows for the rapid generation specifically modified adeno‐associated virus variants, surpassing the time required for natural evolution, which spans millions of years. Notably, these variants exhibit robust targeting of the liver, favouring chimeric human liver cells over murine hepatocytes. Furthermore, certain variants achieve augmented targeting with reduced off‐target organ infection, thereby mitigating dosage requirements and enhancing safety in gene therapy.

Funder

National Key Research and Development Program of China

National Postdoctoral Program for Innovative Talents

Publisher

Wiley

Subject

Cell Biology,General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3