Journal article
The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier
Molecular therapy, v 27(5), pp 912-921
08 May 2019
PMID: 30819613
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Efficient delivery of gene therapy vectors across the blood-brain barrier (BBB) is the holy grail of neurological disease therapies. A variant of the neurotropic vector adeno-associated virus (AAV) serotype 9, called AAV-PHP.B, was shown to very efficiently deliver transgenes across the BBB in C57BL/6J mice. Based on our recent observation that this phenotype is mouse strain dependent, we used whole-exome sequencing-based genetics to map this phenotype to a specific haplotype of lymphocyte antigen 6 complex, locus A (Ly6a) (stem cell antigen-1 [Sca-1]), which encodes a glycosylphosphatidylinositol (GPI)-anchored protein whose function had been thought to be limited to the biology of hematopoiesis. Additional biochemical and genetic studies definitively linked high BBB transport to the binding of AAV-PHP.B with LY6A (SCA-1). These studies identify, for the first time, a ligand for this GPI-anchored protein and suggest a role for it in BBB transport that could be hijacked by viruses in natural infections or by gene therapy vectors to treat neurological diseases.
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Details
- Title
- The GPI-Linked Protein LY6A Drives AAV-PHP.B Transport across the Blood-Brain Barrier
- Creators
- Juliette Hordeaux - University of PennsylvaniaYuan Yuan - University of PennsylvaniaPeter M Clark - University of PennsylvaniaQiang Wang - University of PennsylvaniaR Alexander Martino - University of PennsylvaniaJoshua J Sims - University of PennsylvaniaPeter Bell - University of PennsylvaniaAngela Raymond - University of OttawaWilliam L Stanford - University of OttawaJames M Wilson - University of Pennsylvania
- Publication Details
- Molecular therapy, v 27(5), pp 912-921
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000467247800006
- Scopus ID
- 2-s2.0-85061872188
- Other Identifier
- 991019356343204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biotechnology & Applied Microbiology
- Genetics & Heredity
- Medicine, Research & Experimental