title: Systemic delivery of tyrosine-mutant AAV vectors results in robust transduction of neurons in adult mice.
abstract: Recombinant adeno-associated virus (AAV) vectors are powerful tools for both basic neuroscience experiments and clinical gene therapies for neurological diseases. Intravascularly administered self-complementary AAV9 vectors can cross the blood-brain barrier. However, AAV9 vectors are of limited usefulness because they mainly transduce astrocytes in adult animal brains and have restrictions on foreign DNA package sizes. In this study, we show that intracardiac injections of tyrosine-mutant pseudotype AAV9/3 vectors resulted in extensive and widespread transgene expression in the brains and spinal cords of adult mice. Furthermore, the usage of neuron-specific promoters achieved selective transduction of neurons. These results suggest that tyrosine-mutant AAV9/3 vectors may be effective vehicles for delivery of therapeutic genes, including miRNAs, into the brain and for treating diseases that affect broad areas of the central nervous system.
authors.affiliation: Division of Neurology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Iida
authors.forename: Naomi
authors.initials: N
authors.lastname: Takino
authors.forename: Hitomi
authors.initials: H
authors.lastname: Miyauchi
authors.forename: Kuniko
authors.initials: K
authors.lastname: Shimazaki
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Muramatsu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic; D014443:Tyrosine / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D014443:Tyrosine