An essential receptor for adeno-associated virus infection

Nature
S PillayJ E Carette

Abstract

Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently b...Continue Reading

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Citations

Apr 16, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Candace SummerfordR Jude Samulski
Apr 28, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sourav R ChoudhuryMiguel Sena-Esteves
May 25, 2016·Genome Medicine·Ignazio MaggioManuel A F V Gonçalves
Jan 12, 2017·Human Gene Therapy·Paul N Valdmanis, Mark A Kay
Apr 20, 2017·Nature Reviews. Microbiology·Andreas S PuschnikJan E Carette
Jul 28, 2016·Current Opinion in Virology·Dongsheng Duan
Jun 27, 2017·The Journal of Clinical Investigation·Linde A MilesCharles M Rudin
Dec 9, 2016·Human Gene Therapy·Dolan SondhiRonald G Crystal
Jul 21, 2017·Human Gene Therapy. Clinical Development·Michael G KatzCharles R Bridges
Jan 19, 2018·Journal of Virology·Amanda M DudekLuk H Vandenberghe
Nov 7, 2017·Gene Therapy·L FaleseS Fong
Aug 4, 2018·Gene Therapy·Liujiang SongMatthew L Hirsch
Oct 6, 2017·Prenatal Diagnosis·Marianne S CarlonSusan Birket
Aug 25, 2017·Human Gene Therapy·Dirk Grimm, Hildegard Büning
Jun 20, 2018·Genome Research·Sumana SharmaGavin J Wright
Aug 14, 2018·The Journal of Gene Medicine·Hongling ZhuBrian H Annex
Sep 11, 2018·Biotechnology and Bioengineering·Esther J LeeJunghae Suh
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Feb 12, 2019·Nature Microbiology·Ran ZhangZihe Rao
Feb 23, 2019·Journal of Virology·Yingyuan SunMichael G Rossmann
Mar 1, 2019·British Journal of Pharmacology·Lars M IttnerYazi D Ke
Apr 24, 2019·Viruses·Mario MietzschMavis Agbandje-McKenna
Aug 31, 2016·Nature Microbiology·Sabrina Sun, David V Schaffer

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Methods Mentioned

BETA
fluorescence-activated cell sorting
flow cytometry
PCR
gene-trap
FACS
chip
genotyping
gene trap
ELISA

Software Mentioned

FlowJo
R
SigmaPlot
BIAevaluation
TreeStar

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