title: In vivogene targeting of IL-3 into immature hematopoietic cells through CD117 receptor mediated antibody gene delivery.
abstract: BACKGROUND
  Targeted gene transfection remains a crucial issue to permit the real development of genetic therapy. As such,in vivotargeted transfection of specific subsets of hematopoietic stem cells might help to sustain hematopoietic recovery from bone marrow aplasia by providing local production of growth factors.
  
  
  METHODS
  Balb/C mice were injected intravenously, with an anti-mouse c-kit (CD117) monoclonal antibody chemically coupled to a human IL-3 gene-containing plasmid DNA. Mice were sacrificed for tissue analyses at various days after injection of the conjugates.
  
  
  RESULTS
  By ELISA, the production of human IL-3 was evidenced in the sera of animals 5 days after treatment. Cytofluorometric analysis afterin vivotransfection of a reporter gene eGFP demonstrated transfection of CD117+/Sca1+ hematopoietic immature cells. By PCR analysis of genomic DNA and RNA using primer specific pIL3 sequences, presence and expression of the human IL-3-transgene were detected in the bone marrow up to 10 days in transfected mice but not in control animals.
  
  
  CONCLUSIONS
  These data clearly indicate that antibody-mediated endocytosis gene transfer allows the expression of the IL-3 transgene into hematopoietic immature cells,in vivo. While availability of marketed recombinant growth factors is restricted, this targeting strategy should permit delivery of therapeutic genes to tissues of interest through systemic delivery. In particular, the ability to specifically target growth factor expression into repopulating hematopoietic stem cells may create new opportunities for the treatment of primary or radiation-induced marrow failures.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.|Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
authors.affiliation: Inserm U542 and Paris XI University, Villejuif, France.|Institut Pasteur, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Deas
authors.affiliation: Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.|Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: François
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.|Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Moubarak
authors.initials: M
authors.lastname: Mouiseddine
authors.affiliation: Institut Pasteur, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Poncet
authors.affiliation: Inserm U542 and Paris XI University, Villejuif, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Dürrbach
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Aigueperse
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.affiliation: Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Norbert C
authors.initials: NC
authors.lastname: Gorin
authors.affiliation: Inserm U542 and Paris XI University, Villejuif, France.
authors.forename: François
authors.initials: F
authors.lastname: Hirsch
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection et de santé de l'Homme et de Dosimétrie, Section Autonome de Radiobiologie Appliquée à la Médecine, Fontenay aux roses, France.|Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle, LTCRA, UPRES 1632, CHU Saint Antoine, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Thierry