Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
DOI
PMC
 |
|
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Synthetic AAV/CRISPR vectors for blocking HIV-1 expression in persistently infected astrocytes.
Glia 66, 413-427 (2018)
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes. Analysis of AAV9P1 transduction efficiencies with single brain cell populations, including primary human brain cells, as well as human brain organoids demonstrated that AAV9P1 targeted terminally differentiated human astrocytes much more efficiently than neurons. We then investigated whether AAV9P1 can be used to deliver HIV-inhibitory genes to astrocytes. To this end we generated AAV9P1 vectors containing genes for HIV-1 proviral editing by CRISPR/Cas9. Latently HIV-1 infected astrocytes transduced with these vectors showed significantly diminished reactivation of proviruses, compared with untransduced cultures. Sequence analysis identified mutations/deletions in key HIV-1 transcriptional control regions. We conclude that AAV9P1 is a promising tool for gene delivery to astrocytes and may facilitate inactivation/destruction of persisting HIV-1 proviruses in astrocyte reservoirs.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Crispr/cas9 ; Hiv ; Adeno-associated Viral Vector ; Astrocytes; Central-nervous-system; Human-immunodeficiency-virus; Adenoassociated Virus; Gene-expression; Cell-lines; In-vitro; Neurocognitive Disorders; Neurological Disorders; Crispr/cas9 System; Viral Vectors
ISSN (print) / ISBN
0894-1491
e-ISSN
1098-1136
Zeitschrift
Glia
Quellenangaben
Band: 66,
Heft: 2,
Seiten: 413-427
Verlag
Wiley
Verlagsort
Hoboken
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed