当前位置: X-MOL 学术Bioconjugate Chem. › 论文详情
Programmable Assembly of Adeno-Associated Virus–Antibody Composites for Receptor-Mediated Gene Delivery
Bioconjugate Chemistry ( IF 4.349 ) Pub Date : 2019-12-20 , DOI: 10.1021/acs.bioconjchem.9b00790
Alina C. Zdechlik; Yungui He; Eric J. Aird; Wendy R. Gordon; Daniel Schmidt

Adeno-associated virus (AAV) has emerged as a viral gene delivery vector that is safe in humans, able to infect both dividing and arrested cells and drive long-term expression (>6 months). Unfortunately, the naturally evolved properties of many AAV serotypes—including low cell type specificity and largely overlapping tropism—are mismatched to applications that require cell type-specific infection, such as neural circuit mapping or precision gene therapy. A variety of approaches to redirect AAV tropism exist, but there is still the need for a universal solution for directing AAV tropism toward user-defined cellular receptors that does not require extensive case-by-case optimization and works with readily available components. Here, we report AAV engineering approaches that enable programmable receptor-mediated gene delivery. First, we genetically encode small targeting scaffolds into a variable region of an AAV capsid and show that this redirects tropism toward the receptor recognized by these targeting scaffolds and also renders this AAV variant resistant to neutralizing antibodies present in nonhuman primate serum. We then simplify retargeting of tropism by engineering the same variable loop to encode a HUH tag, which forms a covalent bond to single-stranded DNA oligos conjugated to store-bought antibodies. We demonstrate that retargeting this HUH-AAVs toward different receptors is as simple as “arming” a premade noninfective AAV template with a different antibody in a conjugation process that uses widely available reagents and requires no optimization or extensive purification. Composite antibody–AAV nanoparticles structurally separate tropism and payload encapsulation, allowing each to be engineered independently.
更新日期:2019-12-21

 

全部期刊列表>>
Springer Nature 2019高下载量文章和章节
化学/材料学中国作者研究精选
《科学报告》最新环境科学研究
ACS材料视界
自然科研论文编辑服务
中南大学国家杰青杨华明
南开大学陈弓课题组招聘启事
中南大学
材料化学和生物传感方向博士后招聘
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug