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J Neurovirol
; 26(5): 769-778, 2020 10.
Article
in English
| MEDLINE
| ID: mdl-32839948
ABSTRACT
The blood-brain barrier (BBB) is a major obstacle for the treatment of central nervous system (CNS) disorders. Significant progress has been made in developing adeno-associated virus (AAV) variants with increased ability to cross the BBB in mice. However, these variants are not efficacious in non-human primates. Herein, we employed various bioinformatic techniques to identify lymphocyte antigen-6E (LY6E) as a candidate for mediating transport of AAV across the human BBB based on the previously determined mechanism of transport in mice. Our results provide insight into future discovery and optimization of AAV variants for CNS gene delivery in humans.
Subject(s)
Antigens, Ly/metabolism , Antigens, Surface/metabolism , Blood-Brain Barrier/metabolism , Dependovirus/metabolism , Genetic Vectors/metabolism , Membrane Proteins/metabolism , Receptors, Virus/metabolism , Amino Acid Sequence , Animals , Antigens, Ly/chemistry , Antigens, Ly/genetics , Antigens, Surface/chemistry , Antigens, Surface/genetics , Biological Transport , Blood-Brain Barrier/virology , Capillary Permeability , Cerebral Cortex/blood supply , Cerebral Cortex/cytology , Cerebral Cortex/virology , Computational Biology/methods , Dependovirus/chemistry , Dependovirus/genetics , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelial Cells/virology , GPI-Linked Proteins/chemistry , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Gene Expression , Gene Transfer Techniques , Genetic Therapy/methods , Genetic Vectors/chemistry , Humans , Macaca mulatta , Membrane Proteins/chemistry , Membrane Proteins/genetics , Mice , Models, Molecular , Molecular Docking Simulation , Protein Binding , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/metabolism , Receptors, Virus/chemistry , Receptors, Virus/genetics , Sequence Alignment , Sequence Homology, Amino Acid
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