A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization
文献类型：期刊论文
| 作者 | Luo, Lin-Lin3; Xu, Jie3; Wang, Bing-Qiao7; Chen, Chen4,5; Chen, Xi6; Hu, Qiu-Mei3; Wang, Yu-Qiu5; Zhang, Wan-Yun7; Jiang, Wan-Xiang2; Li, Xin-Ting5 |
| 刊名 | BIOMATERIALS
 |
| 出版日期 | 2024 |
| 卷号 | 304页码:13 |
| ISSN号 | 0142-9612 |
| 关键词 | AAV Capsid engineering Phosphosites mutation Retinal tropism Neovascularization |
| DOI | 10.1016/j.biomaterials.2023.122403 |
| 通讯作者 | Xiao, Xiao(xiaoxiao@beliefbiomed.com) ; Zhao, Kai(zhao-kai@beliefbiomed.com) ; Lin, Sen(sam.lin@tmmu.edu.cn) |
| 英文摘要 | 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 mu-tations, 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. |
| WOS关键词 | HIGH-EFFICIENCY TRANSDUCTION ; MUTANT AAV VECTORS ; MACULAR DEGENERATION ; GENE DELIVERY ; IN-VITRO ; NEUTRALIZING ANTIBODIES ; ANIMAL-MODELS ; OPEN-LABEL ; AGE ; INTRAVITREAL |
| 资助项目 | National Natural Science Foundation of China[31901052] ; Science and Technology Innovation Enhancement Project of Army Medical University[2019CXJSB021] |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCI LTD |
| WOS记录号 | WOS:001126546200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308356]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xiao, Xiao; Zhao, Kai; Lin, Sen |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Media, Analyt Res Ctr Organ & Biol Mol, CAS Key Lab Receptor Res,State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Sichuan Greentech Biosci Co Ltd, Bencao Ave, Meishan 620010, Sichuan, Peoples R China 3.Army Med Univ, Army Med Ctr PLA, Dept Ophthalmol, Chongqing 400042, Peoples R China 4.Belief BioMed Co Ltd, Shanghai 200237, Peoples R China 5.East China Univ Sci & Technol, Sch Bioengn, Shanghai 200237, Peoples R China 6.Chongqing Inst Brain & Intelligence, Guangyang Bay Lab, Chongqing 400064, Peoples R China 7.Army Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing 400042, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Lin-Lin,Xu, Jie,Wang, Bing-Qiao,et al. A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization[J]. BIOMATERIALS,2024,304:13. |
| APA | Luo, Lin-Lin.,Xu, Jie.,Wang, Bing-Qiao.,Chen, Chen.,Chen, Xi.,...&Lin, Sen.(2024).A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization.BIOMATERIALS,304,13. |
| MLA | Luo, Lin-Lin,et al."A novel capsid-XL32-derived adeno-associated virus serotype prompts retinal tropism and ameliorates choroidal neovascularization".BIOMATERIALS 304(2024):13. |
入库方式： OAI收割
来源：上海药物研究所
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