Gene delivery to the mouse brain with adeno-associated virus. 2004

Marco A Passini, and Deborah J Watson, and John H Wolfe
Department of Pathobiology and Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, and Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

The efficient transduction of postmitotic cells by adeno-associated virus (AAV) makes it an excellent vector to deliver marker, functional, or therapeutic genes to the mammalian brain. An attractive feature of AAV is that all the viral-coding sequences are removed when engineering the recombinant genome, thereby limiting the extent of cell toxicity and immune response that are often associated with viral gene transcription. Of the seven described AAV serotypes, AAV serotype-2 (AAV2) is the most studied gene-transfer vehicle for in the mammalian brain. A feature of AAV2 transduction in the brain is that the vector remains confined to the injection site and predominately infects neurons rather than glia (2-8). The limited diffusion of AAV2 vectors is beneficial for controlled gene delivery. For instance, targeting therapeutic genes only to brain structures showing pathology would eliminate complications associated with vector diffusion and subsequent expression in healthy structures, and is an important consideration when designing treatment strategies for localized neurodegenerative diseases. The same is true for other experimental paradigms, such as investigating the function of genes in specific brain structures or using marker genes in tract-tracing experiments. Although AAV2 vectors were shown to remain predominately at the injection site, one study demonstrated that the vector itself may undergo axonal transport in inter-regional systems (9).

UI MeSH Term Description Entries
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D000229 Dependovirus A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2. Adeno-Associated Viruses,Dependoparvovirus,Adeno-Associated Virus,Virus, Adeno-Associated,Viruses, Adeno-Associated,Adeno Associated Virus,Adeno Associated Viruses,Dependoparvoviruses,Dependoviruses,Virus, Adeno Associated,Viruses, Adeno Associated
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018014 Gene Transfer Techniques The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms. Gene Delivery Systems,Gene Transfer Technique,Transgenesis,Delivery System, Gene,Delivery Systems, Gene,Gene Delivery System,Technique, Gene Transfer,Techniques, Gene Transfer,Transfer Technique, Gene,Transfer Techniques, Gene

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