title: Foamy virus-adenovirus hybrid vectors for gene therapy of the arthritides.
abstract: BACKGROUND
  Genetic treatments of chronic arthritic conditions are essentially dependent on safe and efficient vector systems. To combine features of the efficient transduction of adenovirus vectors with the advantage of stable integration into the host cell genome of apathogenic prototype foamy virus vectors, hybrid vectors (FAD) have been established. In the present study, we have generated and investigated the use of safe FAD vectors for direct gene delivery to joints.
  
  
  METHODS
  We generated recombinant FAD encoding enhanced green fluorescent protein (EGFP) or human interleukin 1 receptor antagonist protein (IL1RA) cDNA, and explored their transgene expression profile, as well as the bioactivity of the IL1RA transgene in vitro. The feasibility of IL1RA gene delivery to articular tissues was investigated in a pilot study employing direct FAD injections to the knee joints of Wistar rats.
  
  
  RESULTS
  FAD vectors efficiently transduced human or rat fibroblasts with EGFP or IL1RA transgene in vitro. Levels of IL1RA transgene expression were high, stable and functional in vitro. Transduced synovial fibroblasts and high levels of IL1RA protein (10-35 ng/ml) could be detected in vivo in the synovium of Wistar rats 3-5 days after injection of FAD vectors to the knee joints.
  
  
  CONCLUSIONS
  Our results indicate that FAD vectors are capable of efficient in vivo gene transfer to synovium and merit further investigation as a means of providing efficient and long-term intra-articular transgene expression for treatment of the arthritides.
authors.affiliation: University of Würzburg, Department of Virology and Immunobiology, Würzburg, Germany.
authors.forename: Conrad
authors.initials: C
authors.lastname: Weber
authors.forename: Nicole
authors.initials: N
authors.lastname: Armbruster
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
authors.forename: Florian
authors.initials: F
authors.lastname: Kreppel
authors.forename: Stefan
authors.initials: S
authors.lastname: Kochanek
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.forename: Andre F
authors.initials: AF
authors.lastname: Steinert
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001168:Arthritis / Q000628:therapy*; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016092:Spumavirus / Q000235:genetics*; D013583:Synovial Membrane / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics
chemical_list: D017931:DNA Primers; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins