title: Development of Optimized AAV Serotype Vectors for High-Efficiency Transduction at Further Reduced Doses.
abstract: We have described the development of capsid-modified next-generation AAV vectors for both AAV2 and AAV3 serotypes, in which specific surface-exposed tyrosine (Y), serine (S), threonine (T), and lysine (K) residues on viral capsids were modified to achieve high-efficiency transduction at lower doses. We have also described the development of genome-modified AAV vectors, in which the transcriptionally inactive, single-stranded AAV genome was modified to achieve improved transgene expression. Here, we describe that combination of capsid modifications and genome modifications leads to the generation of optimized AAV serotype vectors, which transduce cells and tissues more efficiently, both in vitro and in vivo, at ∼20-30-fold reduced doses. These studies have significant implications in the potential use of the optimized AAV serotype vectors in human gene therapy.
authors.affiliation: 1 Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine , Gainesville, Florida.|2 Powell Gene Therapy Center, University of Florida College of Medicine , Gainesville, Florida.|3 Shands Cancer Center, University of Florida College of Medicine , Gainesville, Florida.
authors.forename: Chen
authors.initials: C
authors.lastname: Ling
authors.affiliation: 1 Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine , Gainesville, Florida.
authors.forename: Baozheng
authors.initials: B
authors.lastname: Li
authors.affiliation: 1 Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine , Gainesville, Florida.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Ma
authors.affiliation: 1 Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine , Gainesville, Florida.|2 Powell Gene Therapy Center, University of Florida College of Medicine , Gainesville, Florida.|3 Shands Cancer Center, University of Florida College of Medicine , Gainesville, Florida.|4 Genetics Institute, University of Florida College of Medicine , Gainesville, Florida.|5 Department of Molecular Genetics and Microbiology, University of Florida College of Medicine , Gainesville, Florida.
authors.forename: Arun
authors.initials: A
authors.lastname: Srivastava
mesh_terms: D002213:Capsid / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000235:genetics; D012694:Serine / Q000235:genetics; D065288:Serogroup; D013912:Threonine / Q000235:genetics; D014161:Transduction, Genetic; D014443:Tyrosine / Q000235:genetics
chemical_list: D013912:Threonine; D014443:Tyrosine; D012694:Serine; D008239:Lysine