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Gene Therapy / 基因治疗AAV Vectors

Mavis Agbandje-McKenna

Ph.D.

🏢University of Florida (Deceased 2021)(佛罗里达大学(2021年去世))🌐USA

Former Professor of Structural Biology and Director of Center for Structural Biology前结构生物学教授和结构生物学中心主任

3
Key Papers
11
Awards
2
Key Contributions

👥Biography 个人简介

Mavis Agbandje-McKenna, Ph.D. (April 11, 1963 – March 3, 2021), was a Nigerian-born British medical biophysicist, structural virologist, Professor of Structural Biology, and Director of the Center for Structural Biology at the University of Florida in Gainesville, Florida. She passed away at age 57 after a long battle with amyotrophic lateral sclerosis (ALS). Dr. Agbandje-McKenna is internationally recognized as the founding pioneer of AAV structural biology. Beginning in the early 2000s, her laboratory systematically used X-ray crystallography to determine high-resolution three-dimensional structures of multiple AAV serotypes, establishing the "AAV Structural Atlas." Until 2016, virtually all AAV capsid structural characterizations were performed using X-ray crystallography, with Agbandje-McKenna's lab publishing crystallographic studies of AAV1, AAV4, AAV5, AAV7, AAV8, AAV9, and other serotypes. Using advanced imaging techniques including X-ray crystallography and cryogenic electron microscopy, her team mapped the surface structures and symmetry of viral capsid proteins, defining how various AAV types interact with cellular receptors. After 2016, her laboratory transitioned to cryo-EM technology, continuing to resolve additional AAV serotype structures. In January 2021, just two months before her passing, she published "Completion of the AAV Structural Atlas," reporting the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 and revealing clade-specific features—representing the culmination of her life's work. Beyond structural determination, Agbandje-McKenna's research elucidated AAV-receptor binding mechanisms, tissue tropism differences across serotypes, and antibody neutralization sites. Her viral characterization and identification of antibody binding epitopes on AAV capsids directly enabled development of engineered capsid variants that evade immune detection for treating human diseases including muscular dystrophies. Her structural insights provided blueprints for rational AAV vector design, enabling researchers to modify capsids for enhanced specificity, improved transduction efficiency, or immune evasion. In 2020, Agbandje-McKenna received ASGCT's Outstanding Achievement Award, the Society's highest honor. In 2022, ASGCT established the Mavis Agbandje-McKenna Scholarship and Fund to honor her dedication to scientific excellence, love for mentoring, and willingness to collaborate.

Mavis Agbandje-McKenna哲学博士(1963年4月11日-2021年3月3日),是尼日利亚裔英国医学生物物理学家、结构病毒学家、佛罗里达大学结构生物学教授和结构生物学中心主任。她在与肌萎缩侧索硬化症(ALS)长期抗争后,于57岁时去世。 Agbandje-McKenna博士国际公认为AAV结构生物学的奠基先驱。从2000年代初开始,她的实验室系统地使用X射线晶体学确定多个AAV血清型的高分辨率三维结构,建立了"AAV结构图谱"。直到2016年,几乎所有AAV衣壳结构表征都是通过X射线晶体学完成的,Agbandje-McKenna实验室发表了AAV1、AAV4、AAV5、AAV7、AAV8、AAV9等血清型的晶体学研究。 使用包括X射线晶体学和冷冻电子显微镜在内的先进成像技术,她的团队绘制了病毒衣壳蛋白的表面结构和对称性,定义了各种AAV类型如何与细胞受体相互作用。2016年后,她的实验室转向冷冻电镜技术,继续解析更多AAV血清型结构。2021年1月,就在她去世前两个月,她发表了"AAV结构图谱完成",报告了AAV7、AAV11、AAV12和AAV13的剩余衣壳结构并揭示了分支特异性特征——代表了她毕生工作的巅峰。 除了结构测定,Agbandje-McKenna的研究阐明了AAV-受体结合机制、血清型之间的组织趋向性差异和抗体中和位点。她对病毒的表征和对AAV衣壳上抗体结合表位的识别直接促成了工程化衣壳变体的开发,这些变体可以逃避免疫检测以治疗包括肌营养不良在内的人类疾病。她的结构见解为理性AAV载体设计提供了蓝图,使研究人员能够修饰衣壳以增强特异性、提高转导效率或免疫逃避。 2020年,Agbandje-McKenna获得ASGCT杰出成就奖,这是该学会的最高荣誉。2022年,ASGCT设立Mavis Agbandje-McKenna奖学金和基金,以纪念她对科学卓越的奉献、对指导的热爱和合作意愿。

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🧪Research Fields 研究领域

AAV Structural BiologyAAV结构生物学
X-ray CrystallographyX射线晶体学
Cryo-EM冷冻电镜
AAV-Receptor InteractionsAAV-受体相互作用

🎓Key Contributions 主要贡献

Founding Pioneer of AAV Structural Atlas

Founding pioneer of AAV structural biology. From early 2000s, laboratory systematically used X-ray crystallography to resolve high-resolution 3D structures of multiple AAV serotypes, establishing the "AAV Structural Atlas." Until 2016, virtually all AAV capsid structural characterizations were performed using X-ray crystallography, with Agbandje-McKenna lab publishing crystallographic studies of AAV1, AAV4, AAV5, AAV7, AAV8, AAV9, and other serotypes. Team mapped surface structures and symmetry of viral capsid proteins, defining how various AAV types interact with cellular receptors. After 2016, lab transitioned to cryo-EM technology, continuing to resolve additional AAV serotype structures. January 2021 publication "Completion of AAV Structural Atlas" (2 months before her passing) reported remaining capsid structures of AAV7, AAV11, AAV12, and AAV13, representing the culmination of her life's work systematically completing major AAV serotype structural characterization.

AAV-Receptor Binding and Antibody Neutralization Mechanisms

Research not only resolved structures but more importantly revealed structure-function relationships. Team systematically studied AAV-cellular receptor binding mechanisms, tissue tropism differences across serotypes, and antibody neutralization sites. Her viral characterization and elucidation of antibody binding epitopes on AAV capsids directly enabled development of engineered capsid variants that evade immune detection for treating human diseases like muscular dystrophies. Discovered common antibody binding regions across different AAV serotypes; these footprints overlap with known receptor binding sites and transduction determinants, critical for understanding viral neutralization mechanisms. Her structural insights provided blueprints for rational AAV vector variant design, enabling researchers to modify capsids for enhanced specificity, improved transduction efficiency, or immune evasion.

Representative Works 代表性著作

[1]

Structurally mapping the diverse phenotype of adeno-associated virus serotype 4

Journal of Virology (2006)

Reported crystal structure of AAV serotype 4 (AAV4). AAV4 is one of the most diverse serotypes in capsid protein sequence and antigenic reactivity. Study found surface loop variations cause local topological differences on capsid surface, including deeper 2-fold axis depression, wider and rounder 3-fold axis surrounding protrusions, and different 5-fold axis channel top topology versus AAV2. These structural insights provided foundations for understanding AAV serotype diversity.

[2]

Structure of adeno-associated virus serotype 8, a gene therapy vector

Journal of Virology (2007)

Resolved crystal structure of AAV serotype 8 (AAV8) viral capsid at 2.6 Å resolution. AAV8 shows significantly higher liver transduction efficiency and has been developed as a gene therapy vector for hemophilia A and familial hypercholesterolemia. Study found most significant structural differences between AAV8 and AAV2 are located on protrusions around 2-fold, 3-fold, and 5-fold axes on capsid surface, explaining its unique tissue tropism and receptor binding properties.

[3]

Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features

Viruses (2021)

Using cryo-EM and 3D image reconstruction, reported capsid structures of AAV7, AAV11, AAV12, and AAV13 (resolutions 2.96, 2.86, 2.54, and 2.76 Å respectively). This paper completed the AAV structural atlas, revealing clade-specific features. Published two months before her passing, this last major work represents the pinnacle achievement of her lifelong dedication to AAV structural research.

🏆Awards & Recognition 奖项与荣誉

🏆2020 ASGCT Outstanding Achievement Award (Society's highest honor)
🏆Professor of Structural Biology, University of Florida
🏆Director, Center for Structural Biology, UF
🏆2022 Mavis Agbandje-McKenna Scholarship and Fund (established by ASGCT in memoriam)
🏆AAV structural biology field's most important pioneer
🏆Published 150+ AAV structure-related papers
🏆Resolved 10+ AAV serotype high-resolution structures
🏆Created the AAV Structural Atlas
🏆Internationally recognized structural virologist
🏆One of the most cited structural biologists in AAV field
🏆Lifetime dedication to teaching and research

📄Data Sources 数据来源

Last updated: 2026-03-08 | All information from publicly available academic sources

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