title: Extracorporeal delivery of rAAV with metabolic exchange and oxygenation.
abstract: Over the past decade much progress has been made towards the treatment of disease with recombinant adeno-associated viral vectors, ranging from cancer to muscular dystrophies, and autoimmune diseases to cystic fibrosis. Given inherent challenges of vector delivery we developed a system incorporating commercially available dialysis equipment. This concept was evaluated in vitro utilizing rAAV expressing the reporter gene human placental alkaline phosphatase. A number of pre-circulating conditions were assessed. Vector recovery was evaluated by quantitative vector genome analysis and cellular transduction assays. A dialysis circulation time course was established, and results were recorded across varied conditions ranging from approximately 2 to 90% retention of viable vector. This approach is unique in that it focuses on efficient localized, isolated and continual delivery of vector to target tissues, provides for the preservation of tissue integrity with dialysis for metabolic exchange and allows for the transfer of oxygen through a secondary membrane post-dialysis.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA 98195-7720, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Bieber
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Halldorson
authors.forename: Eric
authors.initials: E
authors.lastname: Finn
authors.forename: Suhail
authors.initials: S
authors.lastname: Ahmad
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Chamberlain
authors.forename: Guy L
authors.initials: GL
authors.lastname: Odom
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D015139:Blotting, Southern; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D004573:Electrolytes / Q000097:blood; D015199:Extracorporeal Membrane Oxygenation / Q000295:instrumentation / Q000379:methods*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008254:Macaca nemestrina; D008567:Membranes, Artificial; D008954:Models, Biological; D006435:Renal Dialysis / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D004279:DNA, Viral; D004573:Electrolytes; D058851:GPI-Linked Proteins; D007527:Isoenzymes; D008567:Membranes, Artificial; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental