title: Ex vivo gene delivery to synovium using foamy viral vectors.
abstract: BACKGROUND
  Gene transfer technologies have the potential to fundamentally improve current therapies for arthritic conditions, although this is essentially dependent on safe and efficient vector systems. The foamy virus (FV)-based vectors have many safety features that favour their use in the treatment of arthritis. In the present study, we investigated the use of safe prototype foamy viral vectors (FVV) for indirect gene delivery to articular tissues.
  
  
  METHODS
  We generated recombinant FVV encoding enhanced green fluorescent protein (EGFP) or human interleukin 1 receptor antagonist protein (IL1RA) cDNA under the control of the spleen focus forming virus U3 promoter and explored their transgene expression profile following ex vivo gene delivery to knee joints of Wistar and athymic nude rats.
  
  
  RESULTS
  FVV efficiently transduced primary rat synovial fibroblasts using the EGFP and the IL1RA transgene in vitro. FVV-mediated IL1RA expression was functional in blocking IL1 effects in vitro. After the transplantation of FVV transduced synovial fibroblasts, the intra-articular transgene expression in Wistar rats was initially high and declined after approximately 3 weeks for both transgenes. By contrast, FVV-mediated expression of EGFP and IL1RA persisted for at least 12 weeks at high levels in immunocompromised nude rats. FVV-meditated gene delivery was well tolerated by all animals without extra-articular transgene expression, arguing for the safety of this approach.
  
  
  CONCLUSIONS
  Our results indicate that FVV are capable of efficient ex vivo gene transfer to synovium and merit further investigation as a means to provide long-term intra-articular transgene expression for arthritis treatment.
authors.affiliation: Julius-Maximilians-University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany; Julius-Maximilians-University of Würzburg, Department of Orthopaedic Surgery, König-Ludwig-Haus, Orthopaedic Center for Musculoskeletal Research, Würzburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Armbruster
authors.forename: Conrad
authors.initials: C
authors.lastname: Weber
authors.forename: Tatiana
authors.initials: T
authors.lastname: Wictorowicz
authors.forename: Axel
authors.initials: A
authors.lastname: Rethwilm
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
authors.forename: Andre F
authors.initials: AF
authors.lastname: Steinert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis / Q000235:genetics; D007719:Knee Joint / Q000166:cytology / Q000378:metabolism; D008297:Male; D011923:Rats, Nude; D017208:Rats, Wistar; D016092:Spumavirus / Q000235:genetics*; D013583:Synovial Membrane / Q000166:cytology*; D014161:Transduction, Genetic
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: arthritis; cell therapy; gene delivery; gene therapy; gene transfer; retroviruses; viral vector