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dc.contributor.authorLins-Austin, Bridget
dc.contributor.authorPatel, Saajan
dc.contributor.authorMietzsch, Mario
dc.contributor.authorBrooke, Dewey
dc.contributor.authorBennett, Antonette
dc.contributor.authorVenkatakrishnan, Balasubramanian
dc.contributor.authorVan Vliet, Kim
dc.contributor.authorSmith, Adam N.
dc.contributor.authorLong, Joanna R.
dc.contributor.authorMcKenna, Robert
dc.contributor.authorPotter, Mark
dc.contributor.authorByrne, Barry
dc.contributor.authorBoye, Sanford L.
dc.contributor.authorBothner, Brian
dc.contributor.authorHeilbronn, Regine
dc.contributor.authorAgbandje-McKenna, Mavis
dc.date.accessioned2022-02-14T18:53:00Z
dc.date.available2022-02-14T18:53:00Z
dc.date.issued2020-06
dc.identifier.citationLins-Austin, Bridget, Saajan Patel, Mario Mietzsch, Dewey Brooke, Antonette Bennett, Balasubramanian Venkatakrishnan, Kim Van Vliet, et al. “Adeno-Associated Virus (AAV) Capsid Stability and Liposome Remodeling During Endo/Lysosomal pH Trafficking.” Viruses 12, no. 6 (June 20, 2020): 668. doi:10.3390/v12060668en_US
dc.identifier.issn1999-4915
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/16664
dc.description.abstractAdeno-associated viruses (AAVs) are small, non-pathogenic ssDNA viruses being used as therapeutic gene delivery vectors for the treatment of a variety of monogenic diseases. An obstacle to successful gene delivery is inefficient capsid trafficking through the endo/lysosomal pathway. This study aimed to characterize the AAV capsid stability and dynamics associated with this process for a select number of AAV serotypes, AAV1, AAV2, AAV5, and AAV8, at pHs representative of the early and late endosome, and the lysosome (6.0, 5.5, and 4.0, respectively). All AAV serotypes displayed thermal melt temperatures that varied with pH. The stability of AAV1, AAV2, and AAV8 increased in response to acidic conditions and then decreased at pH 4.0. In contrast, AAV5 demonstrated a consistent decrease in thermostability in response to acidification. Negative-stain EM visualization of liposomes in the presence of capsids at pH 5.5 or when heat shocked showed induced remodeling consistent with the externalization of the PLA2 domain of VP1u. These observations provide clues to the AAV capsid dynamics that facilitate successful infection. Finally, transduction assays revealed a pH and temperature dependence with low acidity and temperatures > 4 °C as detrimental factors.en_US
dc.language.isoen_USen_US
dc.rights© 2020 This final published version is made available under the CC-BY 4.0 license.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleAdeno-Associated Virus (AAV) Capsid Stability and Liposome Remodeling During Endo/Lysosomal pH Traffickingen_US
dc.typeArticleen_US
mus.citation.extentfirstpage668en_US
mus.citation.issue6en_US
mus.citation.journaltitleVirusesen_US
mus.citation.volume12en_US
mus.identifier.doi10.3390/v12060668en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentChemistry & Biochemistry.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage11en_US


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© 2020 This final published version is made available under the CC-BY 4.0 license.
Except where otherwise noted, this item's license is described as © 2020 This final published version is made available under the CC-BY 4.0 license.

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