Mavis Agbandje-McKenna

Mavis Agbandje-McKenna (April 11, 1963 – March 3, 2021) was a Nigerian-born British medical biophysicist, structural virologist, and a professor of structural biology, as well as the director of the Center for Structural Biology at the University of Florida in Gainesville, Florida. Agbandje-McKenna studied parvovirus structures using X-ray crystallography and cryogenic electron microscopy and did much of the initial work to elucidate the basic structure and function of adeno-associated viruses (AAVs). Her viral characterization and elucidation of antibody binding sites on AAV capsids has led to the development of viral capsid development and gene therapy approaches that evade immune detection and can be used to treat human diseases such as muscular dystrophies. Agbandje-McKenna was recognized with the 2020 American Society of Gene and Cell Therapy Outstanding Achievement Award for her contributions to the field. She died in 2021 from amyotrophic lateral sclerosis ("Lou Gehrig's disease").

Early life and education Mavis Agbandje was born in Nigeria, and lived with her grandmother until the age of 12 when the civil war broke out. At 13, she left Nigeria and moved to London where her parents lived at the time.

Agbandje conducted her undergraduate education at the University of Hertfordshire in Hatfield in the United Kingdom.

She then pursued her graduate training at the University of London Institute of Cancer Research. Her PhD training focused on Biophysics. During her PhD, she characterized the DNA binding characteristics of Anthracene-9,10-diones to explore their cytotoxic properties and potential in cancer therapy. She completed her PhD training in 1989. In 2005, Agbandje-McKenna was promoted to associate professor, and in 2009, she became a full professor as well as the director of the Center for Structural Biology. Using advanced and high resolution imaging techniques, such as cryogenic electron microscopy and X-ray crystallography, her lab is able to determine the structure of AAV capsids and use this information to understand their life cycle and explore their potential use in gene therapy. This was the first time that a self-assembled empty viral capsid grown in an atypical host system (baculovirus system) had been crystallized.

In 2008, Agbandje-McKenna and her colleagues sought to find improved methods of AAV capsid design for gene therapy since current approaches require large amounts of vector to be effective. They discovered that a specific type of tyrosine kinase signalling impairs the transduction of AAV2, such that when the surface-exposed tyrosine residues on the viral capsid are phosphorylated, the virus can enter the cell, but not begin to express its genetic material. They used a technique called contrast transfer function (CTF) as well as a correction for Ewald sphere curvature and they were able to obtain the highest resolution structural analysis of AAV2 yet. Agbandje-McKenna and her colleagues at UF sought to find a way to prevent host mediated attack of vectors used in gene therapy. Since antibody binding sites are highly conserved across AAVs, they innovated a solution to the problem of host immune attack by designing a structure-guided evolution approach to identify antigenic epitopes on AAVs that are capable of evading neutralizing antibodies from the immune system. She further observed capsid-antibody interactions using cryo-EM at this high resolution and then was able to use her tool to develop novel antigens for AAV5 that evade the immune response. Stridebio focuses on the design of antibody-evading AAV capsids to use in gene therapy for various diseases. Stridebio began collaborating with Takeda to innovate approaches for gene therapy for Friedrich Ataxia. 2018, University of Florida Innovator of the Year 2017, Basic Science Award Recipient 2009, James P. Holland Series Lecturer 2008–2014, UF College of Medicine Outstanding Teacher Award and/or Exemplary Teacher Award 2006, Featured in Findings, a National Institutes of General Medical Sciences Publication Bennett A, Keravala A, Makal V, Kurian J, Belbellaa B, Aeran R, Tseng YS, Sousa D, Spear J, Gasmi M, Agbandje-McKenna M. 2019 Structure comparison of the chimeric AAV2.7m8 vector with parental AAV2. Journal of Structural Biology. 107433. PMID 31859208 DOI: 10.1016/j.jsb.2019.107433 Guenther CM, Brun MJ, Bennett AD, Ho ML, Chen W, Zhu B, Lam M, Yamagami M, Kwon S, Bhattacharya N, Sousa D, Evans AC, Voss J, Sevick-Muraca EM, Agbandje-McKenna M, et al. 2019. Protease-Activatable Adeno-Associated Virus Vector for Gene Delivery to Damaged Heart Tissue. Molecular Therapy : the Journal of the American Society of Gene Therapy. PMID 30772143 DOI: 10.1016/j.ymthe.2019.01.015 Jose A, Mietzsch M, Smith K, Kurian J, Chipman P, McKenna R, Chiorini J, Agbandje-McKenna M. 2018. High resolution structural characterization of a new AAV5 antibody epitope toward engineering antibody resistant recombinant gene delivery vectors. Journal of Virology. PMID 30333169 DOI: 10.1128/JVI.01394-18 Mietzsch M, Agbandje-McKenna M. 2017. The Good That Viruses Do. Annual Review of Virology. 4: iii-v. PMID 28961414 DOI: 10.1146/annurev-vi-04-071217-100011 Tseng YS, Vliet KV, Rao L, McKenna R, Byrne BJ, Asokan A, Agbandje-McKenna M. 2016. Generation and characterization of anti-AAV8 and anti-AAV9 monoclonal antibodies. Journal of Virological Methods. PMID 27424005 DOI: 10.1016/j.jviromet.2016.07.009 Kailasan S, Halder S, Gurda B, Bladek H, Chipman PR, McKenna R, Brown K, Agbandje-McKenna M. 2015. Structure of an enteric pathogen, bovine parvovirus. Journal of Virology. 89: 2603–14. PMID 25520501 DOI: 10.1128/JVI.03157-14 Halder S, Cotmore S, Heimburg-Molinaro J, Smith DF, Cummings RD, Chen X, Trollope AJ, North SJ, Haslam SM, Dell A, Tattersall P, McKenna R, Agbandje-McKenna M. 2014. Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition. PLOS ONE. 9: e86909. PMID 24475195 DOI: 10.1371/journal.pone.0086909 Govindasamy L, DiMattia MA, Gurda BL, Halder S, McKenna R, Chiorini JA, Muzyczka N, Zolotukhin S, Agbandje-McKenna M. 2013. Structural insights into adeno-associated virus serotype 5. Journal of Virology. 87: 11187–99. PMID 23926356 DOI: 10.1128/JVI.00867-13 Quesada O, Gurda B, Govindasamy L, McKenna R, Kohlbrenner E, Aslanidi G, Zolotukhin S, Muzyczka N, Agbandje-McKenna M. Production, purification and preliminary X-ray crystallographic studies of adeno-associated virus serotype 7. 2007. Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 63: 1073–6. PMID 18084098 DOI: 10.1107/S1744309107060289 DiMattia M, Govindasamy L, Levy HC, Gurda-Whitaker B, Kalina A, Kohlbrenner E, Chiorini JA, McKenna R, Muzyczka N, Zolotukhin S, Agbandje-McKenna M. 2005. Production, purification, crystallization and preliminary X-ray structural studies of adeno-associated virus serotype 5. Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 61: 917–21. PMID 16511195 DOI: 10.1107/S1744309105028514 Agbandje M, Jenkins TC, McKenna R, Reszka AP, Neidle S. Anthracene-9,10-diones as potential anticancer agents. 1992. Synthesis, DNA-binding, and biological studies on a series of 2,6-disubstituted derivatives. Journal of Medicinal Chemistry. 35: 1418–29. PMID 1573635 Agbandje M, McKenna R, Rossmann MG, Kajigaya S, Young NS. Preliminary X-ray crystallographic investigation of human parvovirus B19. 1991. Virology. 184: 170–4. PMID 1871964