title: Characterization of a novel adeno-associated viral vector with preferential oligodendrocyte tropism.
abstract: No adeno-associated virus (AAV) capsid has been described in the literature to exhibit a primary oligodendrocyte tropism when a constitutive promoter drives gene expression, which is a significant barrier for efficient in vivo oligodendrocyte gene transfer. The vast majority of AAV vectors, such as AAV1, 2, 5, 6, 8 or 9, exhibit a dominant neuronal tropism in the central nervous system. However, a novel AAV capsid (Olig001) generated using capsid shuffling and directed evolution was recovered after rat intravenous delivery and subsequent capsid clone rescue, which exhibited a >95% tropism for striatal oligodendrocytes after rat intracranial infusion where a constitutive promoter drove gene expression. Olig001 contains a chimeric mixture of AAV1, 2, 6, 8 and 9, but unlike these parental serotypes after intravenous administration Olig001 has very low affinity for peripheral organs, especially the liver. Furthermore, in mixed glial cell cultures, Olig001 exhibits a 9-fold greater binding when compared with AAV8. This novel oligodendrocyte-preferring AAV vector exhibits characteristics that are a marked departure from previously described AAV serotypes.
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Powell
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.
authors.forename: N
authors.initials: N
authors.lastname: Khan
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Parker
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.|Department of Pharmacology, Chapel Hill, NC, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Samulski
authors.affiliation: Department of Microbiology and Immunology, Chapel Hill, NC, USA.
authors.forename: G
authors.initials: G
authors.lastname: Matsushima
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.|Department of Ophtalmology, Chapel Hill, NC, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gray
authors.affiliation: Gene Therapy Center, Chapel Hill, NC, USA.|Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: McCown
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D057967:Infusions, Intraventricular; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D036022:Capsid Proteins