Structure of neurotropic adeno-associated virus AAVrh.8

Journal of Structural Biology
Sujata HalderMavis Agbandje-McKenna

Abstract

Adeno-associated virus rhesus isolate 8 (AAVrh.8) is a leading vector for the treatment of neurological diseases due to its efficient transduction of neuronal cells and reduced peripheral tissue tropism. Toward identification of the capsid determinants for these properties, the structure of AAVrh.8 was determined by X-ray crystallography to 3.5 Å resolution and compared to those of other AAV isolates. The capsid viral protein (VP) structure consists of an αA helix and an eight-stranded anti-parallel β-barrel core conserved in parvoviruses, and large insertion loop regions between the β-strands form the capsid surface topology. The AAVrh.8 capsid exhibits the surface topology conserved in all AAVs: depressions at the icosahedral twofold axis and surrounding the cylindrical channel at the fivefold axis, and three protrusions around the threefold axis. A structural comparison to serotypes AAV2, AAV8, and AAV9, to which AAVrh.8 shares ∼ 84%, ∼ 91%, and ∼ 87% VP sequence identity, respectively, revealed differences in the surface loops known to affect receptor binding, transduction efficiency, and antigenicity. Consistent with this observation, biochemical assays showed that AAVrh.8 is unable to bind heparin and does not cross-react...Continue Reading

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Citations

Aug 31, 2016·Scientific Reports·Lifang SunYunkun Wu
Feb 12, 2019·Nature Microbiology·Ran ZhangZihe Rao
Apr 24, 2019·Viruses·Mario MietzschMavis Agbandje-McKenna
Dec 13, 2019·Journal of Virology·Mario MietzschMavis Agbandje-McKenna
May 10, 2018·Frontiers in Cellular Neuroscience·Stefan KeplingerLars Kunz
Feb 27, 2020·Journal of Clinical Medicine·Fabian BlancJing Wang
Jul 3, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Michael F NasoWilliam R Strohl
May 20, 2018·Journal of Neurodevelopmental Disorders·Erik Allen LykkenSteven James Gray
Apr 5, 2021·Journal of Pharmaceutical Sciences·Arvind SrivastavaGer Brophy
May 1, 2021·Scientific Reports·Mika ItoShin-Ichi Muramatsu
Apr 19, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sanford L BoyeShannon E Boye
Jun 4, 2020·Molecular Therapy. Methods & Clinical Development·Marti Cabanes-CreusLeszek Lisowski

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