UNIVERSI
TÄ
TS-
BIBLIOTHEK
P
ADERBORN
Anmelden
Menü
Menü
Start
Hilfe
Blog
Weitere Dienste
Neuerwerbungslisten
Fachsystematik Bücher
Erwerbungsvorschlag
Bestellung aus dem Magazin
Fernleihe
Einstellungen
Sprache
Deutsch
Deutsch
Englisch
Farbschema
Hell
Dunkel
Automatisch
Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist
gegebenenfalls
nur via VPN oder Shibboleth (DFN-AAI) möglich.
mehr Informationen...
Universitätsbibliothek
Katalog
Suche
Details
Zur Ergebnisliste
Ergebnis 21 von 220
Datensatz exportieren als...
BibTeX
Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant -7m8
Biotechnology and bioengineering, 2016-12, Vol.113 (12), p.2712-2724
Khabou, Hanen
Desrosiers, Mélissa
Winckler, Céline
Fouquet, Stéphane
Auregan, Gwenaëlle
Bemelmans, Alexis-Pierre
Sahel, José-Alain
Dalkara, Deniz
2016
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Khabou, Hanen
Desrosiers, Mélissa
Winckler, Céline
Fouquet, Stéphane
Auregan, Gwenaëlle
Bemelmans, Alexis-Pierre
Sahel, José-Alain
Dalkara, Deniz
Titel
Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant -7m8
Ist Teil von
Biotechnology and bioengineering, 2016-12, Vol.113 (12), p.2712-2724
Ort / Verlag
United States: Blackwell Publishing Ltd
Erscheinungsjahr
2016
Quelle
Access via Wiley Online Library
Beschreibungen/Notizen
ABSTRACT Recently, we described a modified AAV2 vector—AAV2‐7m8—having a capsid‐displayed peptide insertion of 10 amino acids with enhanced retinal transduction properties. The insertion of the peptide referred to as 7m8 is responsible for high‐level gene delivery into deep layers of the retina when virus is delivered into the eye's vitreous. Here, we further characterize AAV2‐7m8 mediated gene delivery to neural tissue and investigate the mechanisms by which the inserted peptide provides better transduction away from the injection site. First, in order to understand if the peptide exerts its effect on its own or in conjunction with the neighboring amino acids, we inserted the 7m8 peptide at equivalent positions on three other AAV capsids, AAV5, AAV8, and AAV9, and evaluated its effect on their infectivity. Intravitreal delivery of these peptide insertion vectors revealed that only AAV9 benefited from 7m8 insertion in the context of the retina. We then investigated AAV2‐7m8 and AAV9‐7m8 properties in the brain, to better evaluate the spread and efficacy of viral transduction in view of the peptide insertion. While 7m8 insertion led to higher intensity gene expression, the spread of gene expression remained unchanged compared to the parental serotypes. Our results indicate that the 7m8 peptide insertion acts by increasing efficacy of cellular entry, with little effect on the spread of viral particles in neural tissue. The effects of peptide insertion are capsid and tissue dependent, highlighting the importance of the microenvironment in gene delivery using AAV. Biotechnol. Bioeng. 2016;113: 2712–2724. © 2016 Wiley Periodicals, Inc. The authors recently described AAV2‐7m8, a vector that outperforms other vectors described for retinal transduction of mouse and primate retina. It is characterized by the insertion of a 10‐amino acid peptide referred to as 7m8. Here, Khabou and coworkers provide insight into the mechanisms for its enhanced gene delivery properties. They used in vitro and in vivo analyses to demonstrate increased cell entry of the particles and enhanced infectivity in transduced cells and tissues, both resulting in higher transgene expression levels.
Sprache
Englisch
Identifikatoren
ISSN: 0006-3592
eISSN: 1097-0290
DOI: 10.1002/bit.26031
Titel-ID: cdi_hal_primary_oai_HAL_hal_01346351v1
Format
–
Schlagworte
AAV
,
Adeno-associated virus
,
Amino acids
,
Animals
,
Bioengineering
,
Biotechnology
,
Capsid Proteins - chemistry
,
Capsid Proteins - genetics
,
Capsid Proteins - ultrastructure
,
Dependovirus - chemistry
,
Dependovirus - genetics
,
Dependovirus - ultrastructure
,
directed evolution
,
Effectiveness
,
gene delivery
,
Gene expression
,
gene therapy
,
Genes
,
Genetic Variation - genetics
,
Genetic Vectors - genetics
,
Genetics
,
HEK293 Cells
,
Humans
,
Insertion
,
Life Sciences
,
Mice
,
Mice, Inbred C57BL
,
Molecular Conformation
,
Peptides
,
Recombinant Proteins - genetics
,
Recombinant Proteins - metabolism
,
Retina
,
Retina - physiology
,
Retina - virology
,
Transduction, Genetic - methods
Weiterführende Literatur
Empfehlungen zum selben Thema automatisch vorgeschlagen von
bX