衣壳
腺相关病毒
病毒学
向性
视网膜
中和抗体
基因传递
脉络膜新生血管
遗传增强
生物
人口
病毒
载体(分子生物学)
医学
基因
遗传学
重组DNA
生物化学
环境卫生
作者
Linlin Luo,Jie Xu,Bing-Qiao Wang,Chen Chen,Xi Chen,Qiumei Hu,Yuqiu Wang,Wan-Yun Zhang,Wanxiang Jiang,X Y Li,Hu Zhou,Xiao Xiao,Kai Zhao,Sen Lin
出处
期刊:Biomaterials
[Elsevier]
日期:2023-11-17
卷期号:304: 122403-122403
标识
DOI:10.1016/j.biomaterials.2023.122403
摘要
Gene therapy has been adapted, from the laboratory to the clinic, to treat retinopathies. In contrast to subretinal route, intravitreal delivery of AAV vectors displays the advantage of bypassing surgical injuries, but the viral particles are more prone to be nullified by the host neutralizing factors. To minimize such suppression of therapeutic effect, especially in terms of AAV2 and its derivatives, we introduced three serine-to-glycine mutations, based on the phosphorylation sites identified by mass spectrum analysis, to the XL32 capsid to generate a novel serotype named AAVYC5. Via intravitreal administration, AAVYC5 was transduced more effectively into multiple retinal layers compared with AAV2 and XL32. AAVYC5 also enabled successful delivery of anti-angiogenic molecules to rescue laser-induced choroidal neovascularization and astrogliosis in mice and non-human primates. Furthermore, we detected fewer neutralizing antibodies and binding IgG in human sera against AAVYC5 than those specific for AAV2 and XL32. Our results thus implicate this capsid-optimized AAVYC5 as a promising vector suitable for a wide population, particularly those with undesirable AAV2 seroreactivity.
科研通智能强力驱动
Strongly Powered by AbleSci AI