title: Altering AAV tropism with mosaic viral capsids.
abstract: Over the past decade, AAV-based vectors have emerged as promising candidates for gene therapeutic applications. Despite the broad tropism of the first eight serotypes identified, certain cell types are refractory to transduction with AAV-based vectors. Furthermore, for certain applications the targeting of specific cell types is desirable. To improve on present methods to alter AAV2 tropism, we take advantage of AAV2 mosaics. Here, we show that AAV2 mosaics have improved infectivity compared with all-mutant virions. Using an AAV2 mutant that contains the immunoglobulin-binding Z34C fragment of protein A, we demonstrate the utility of AAV2 mosaics to alter AAV2 tropism. This system allows us to transduce selectively and efficiently MO7e and Jurkat cells. The use of AAV2 mosaics with a protein A fragment inserted into their capsid, together with targeting antibodies, is a versatile method that allows the specific transduction of a wide array of cell types.
authors.affiliation: Department of Gene and Cell Medicine, Cell and Developmental Biology, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029-6574, USA.
authors.forename: Laure
authors.initials: L
authors.lastname: Gigout
authors.forename: Patricia
authors.initials: P
authors.lastname: Rebollo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Clement
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Warrington
authors.forename: Nicholas
authors.initials: N
authors.lastname: Muzyczka
authors.forename: R Michael
authors.initials: RM
authors.lastname: Linden
authors.forename: Thomas
authors.initials: T
authors.lastname: Weber
mesh_terms: D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009154:Mutation; D013205:Staphylococcal Protein A / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D036022:Capsid Proteins; D013205:Staphylococcal Protein A