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Status: Bibliographieeintrag

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Verfasst von:Cheng, Ming [VerfasserIn]   i
 Dietz, Laura [VerfasserIn]   i
 Gong, Yi [VerfasserIn]   i
 Eichler, Florian [VerfasserIn]   i
 Nammour, Josette [VerfasserIn]   i
 Ng, Carrie [VerfasserIn]   i
 Grimm, Dirk [VerfasserIn]   i
 Maguire, Casey A. [VerfasserIn]   i
Titel:Neutralizing antibody evasion and transduction with purified extracellular vesicle-enveloped adeno-associated virus vectors
Verf.angabe:Ming Cheng, Laura Dietz, Yi Gong, Florian Eichler, Josette Nammour, Carrie Ng, Dirk Grimm, Casey A. Maguire
E-Jahr:2021
Jahr:16 Dec 2021
Umfang:14 S.
Fussnoten:Online ahead of editing: August 27, 2021 ; Gesehen am 27.01.2022
Titel Quelle:Enthalten in: Human gene therapy
Ort Quelle:New York, NY : Liebert, 1990
Jahr Quelle:2021
Band/Heft Quelle:32(2021), 23-24, Seite 1457-1470
ISSN Quelle:1557-7422
Abstract:Adeno-associated virus (AAV) is classified as a nonenveloped DNA virus. However, several years ago, we discovered that in media of packaging cells producing recombinant AAV vectors, AAV capsids can associate with the interior and surface of extracellular vesicles (EVs), sometimes referred to as exosomes. Since then, we and others have demonstrated that exosome-enveloped AAV, exo-AAV, can enhance transduction in vivo as well as evade neutralizing antibodies. - - While promising, these data were generated with differential centrifugation to pellet the exo-AAV. This method results in a heterogeneous mixture of exo-AAV, coprecipitating proteins, as well as free AAV capsids. To define the properties of exo-AAV more accurately, in this study, we used a density gradient method to purify exo-AAV. We next performed head-to-head comparisons of standard AAV1, differential centrifuged exo-AAV1, and gradient purified exo-AAV1 for antibody evasion and transgene expression in the murine brain. We found purified exo-AAV1 to be more resistant to neutralizing antibodies than the other AAV preparations. Direct intracranial injection of purified exo-AAV1 into mice resulted in robust transduction, which transduced a larger area of brain than standard AAV1. We also identified the recently described membrane-associated accessory protein by mass spectrometry of purified exo-AAV1 preparations. Finally, we used a scalable method, size-exclusion chromatography to isolate exo-AAV1, and demonstrated functional transduction in cultured cells and increased antibody resistance. Together, these data suggest that higher purity exo-AAV will have beneficial characteristics for gene delivery and also may lead to mechanistic insights into the incorporation of AAV into EVs.
DOI:doi:10.1089/hum.2021.122
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1089/hum.2021.122
 Volltext: https://www.liebertpub.com/doi/10.1089/hum.2021.122
 DOI: https://doi.org/10.1089/hum.2021.122
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:adeno-associated virus
 exosomes
 extracellular vesicles
 immune-evasion
 neutralizing antibodies
 scalable purification
K10plus-PPN:1787292746
Verknüpfungen:→ Zeitschrift

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