title: Adeno-associated virus (AAV) gene delivery in stem cell therapy.
abstract: The past 30 years have witnessed the development of cell and gene therapies for the treatment of diverse human diseases. Each of these approaches has inherent advantages and disadvantages; however, the two methods align in that, essentially, they are both methods of foreign DNA delivery to complement, eradicate, or supplement nucleotide sequences important for human health. As discussed herein, the combination of these therapies (gene therapy in stem cells), particularly in an ex vivo context, offers powerful genetic engineering which is applicable to the treatment of both genetic and acquired maladies ranging from blood diseases to the treatment of HIV infection. Of the existing gene therapy approaches, including non-viral and viral vectors, those based on adeno-associated virus (AAV) are currently at the forefront as they have been safely used in hundreds of clinical trials and have demonstrated remarkable success in treating blindness and hemophilia B. However, AAV vectors used in combination with cell-based therapies have not transitioned to the clinic. Instead, adenoviral, retroviral, and lentiviral vectors are the preferred choice for the modification of stem cells prior to patient infusion. This review provides a general background of AAV gene therapy and cell therapies, and highlights reports demonstrating apparently conflicting data of productive transduction and vector-induced toxicity using recombinant AAV in stem and stem-like cells.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Nolan J
authors.initials: NJ
authors.lastname: Brown
authors.affiliation: Gene Therapy Center, University of North Carolina at Chapel Hill, NC 27599, USA.|Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 27599, USA.|Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Hirsch
mesh_terms: D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D000229:Dependovirus / Q000235:genetics / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006402:Hematologic Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006801:Humans; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic / Q000379:methods*