title: Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.
abstract: Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo.
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .|2 Interdisciplinary Nanoscience Center (iNANO) and Department of Molecular Biology and Genetics, Aarhus University , Denmark .
authors.forename: Maria
authors.initials: M
authors.lastname: Jakobsen
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Askou
authors.affiliation: 3 Department of Dermatology, Aarhus University Hospital , Aarhus, Denmark .
authors.forename: Karin
authors.initials: K
authors.lastname: Stenderup
authors.affiliation: 3 Department of Dermatology, Aarhus University Hospital , Aarhus, Denmark .
authors.forename: Cecilia
authors.initials: C
authors.lastname: Rosada
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnæs-Hansen
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Jensen
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Corydon
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Jacob Giehm
authors.initials: JG
authors.lastname: Mikkelsen
authors.affiliation: 1 Department of Biomedicine, Aarhus University , Denmark .
authors.forename: Lars
authors.initials: L
authors.lastname: Aagaard
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000145:classification* / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D011401:Promoter Regions, Genetic; D065288:Serogroup; D012867:Skin / Q000378:metabolism*; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous