title: Novel adeno-associated viruses derived from pig tissues transduce most major organs in mice.
abstract: Recently, development of Adeno-associated virus (AAV) vectors has been focusing on expanding the genetic diversity of vectors from existing sequences via directed evolution or epitope remapping. Apart from intelligent design, AAV isolation from natural sources remains an important source of new AAVs with unique biological features. In this study, several new AAV sequences were isolated from porcine tissues (AAVpo2.1, -po4, -po5, and -po6), which aligned in divergent new clades. Viral particles generated from these sequences displayed tissue tropism and transduction efficiency profile specific to each porcine-derived AAV. When delivered systemically, AAVpo2.1 targeted the heart, kidney, and muscle, AAVpo5 performed poorly but was able to transduce muscle fibers when injected intramuscularly, whereas AAVpo4 and -po6 efficiently transduced all the major organs sampled, contending with 'gold-standard' AAVs. When delivered systemically, AAVpo4 and -po6 were detected by polymerase chain reaction (PCR) and histochemical staining of the transgene product in adult mouse brain, suggesting that these vectors can pass through the blood-brain barrier with efficiencies that may be useful for the development of therapeutic approaches. Porcine tissues are antigenically similar to human tissues and by inference, porcine AAVs may provide fresh tools to contribute to the development of gene therapy-based solutions to human diseases.
authors.affiliation: 1] Public Health Agency of Canada, National Microbiology Laboratory, Special Pathogens Program, Winnipeg, Canada [2] University of Manitoba, Department of Medical Microbiology.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bello
authors.affiliation: 1] Public Health Agency of Canada, National Microbiology Laboratory, Special Pathogens Program, Winnipeg, Canada [2] University of Manitoba, Department of Medical Microbiology.
authors.forename: Allan
authors.initials: A
authors.lastname: Chand
authors.affiliation: 1] Public Health Agency of Canada, National Microbiology Laboratory, Special Pathogens Program, Winnipeg, Canada [2] Department of Immunology, Winnipeg, Canada.
authors.forename: Jenna
authors.initials: J
authors.lastname: Aviles
authors.affiliation: Public Health Agency of Canada, National Microbiology Laboratory, Special Pathogens Program, Winnipeg, Canada.
authors.forename: Geoff
authors.initials: G
authors.lastname: Soule
authors.affiliation: 1] Telethon Institute of Genetics and Medicine, Naples, Italy [2] Medical Genetics, Translational Medicine, "Federico II" University, Naples, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.affiliation: 1] Public Health Agency of Canada, National Microbiology Laboratory, Special Pathogens Program, Winnipeg, Canada [2] University of Manitoba, Department of Medical Microbiology [3] Department of Immunology, Winnipeg, Canada.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Kobinger
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D014644:Genetic Variation; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009928:Organ Specificity; D034421:Sus scrofa; D013552:Swine; D014161:Transduction, Genetic; D056189:Viral Tropism / Q000235:genetics*