title: Evaluation of tetrafunctional block copolymers as synthetic vectors for lung gene transfer.
abstract: In the present study, we evaluated, in mice, the efficacy of the tetrafunctional block copolymer 704 as a nonviral gene delivery vector to the lungs. SPECT/CT molecular imaging of gene expression, biochemical assays, and immunohistochemistry were used. Our dataset shows that the formulation 704 resulted in higher levels of reporter gene expression than the GL67A formulation currently being used in a clinical trial in cystic fibrosis patients. The inflammatory response associated with this gene transfer was lower than that induced by the GL67A formulation, and the 704 formulation was amenable to repeated administrations. The cell types transfected by the 704 formulation were type I and type II pneumocytes, and transgene expression could not be detected in macrophages. These results emphasize the relevance of the 704 formulation as a nonviral gene delivery vector for lung gene therapy. Further studies will be required to validate this vector in larger animals, in which the lungs are more similar to human lungs.
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Peggy
authors: P
authors: Richard-Fiardo
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Catherine
authors: C
authors: Hervouet
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Robert
authors: R
authors: Marsault
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Philippe R
authors: PR
authors: Franken
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Béatrice
authors: B
authors: Cambien
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Julien
authors: J
authors: Guglielmi
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Julie
authors: J
authors: Warnez-Soulie
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Jacques
authors: J
authors: Darcourt
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France.
authors: Thierry
authors: T
authors: Pourcher
authors: INSERM UMR1087, CNRS UMR 6291, Nantes, France; Université de Nantes, l'institut du thorax, Nantes, France.
authors: Thibault
authors: T
authors: Colombani
authors: INSERM UMR1087, CNRS UMR 6291, Nantes, France; Université de Nantes, l'institut du thorax, Nantes, France.
authors: Thomas
authors: T
authors: Haudebourg
authors: INSERM UMR1087, CNRS UMR 6291, Nantes, France; Université de Nantes, l'institut du thorax, Nantes, France.
authors: Pauline
authors: P
authors: Peuziat
authors: INSERM UMR1087, CNRS UMR 6291, Nantes, France; Université de Nantes, l'institut du thorax, Nantes, France.
authors: Bruno
authors: B
authors: Pitard
authors: Laboratoire TIRO, UMRE 4320, iBEB, DSV, CEA, Nice, France; Université de Nice-Sophia Antipolis, Nice, France. Electronic address: vassaux@unice.fr.
authors: Georges
authors: G
authors: Vassaux
mesh_terms: D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry*; D027981:Symporters / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014162:Transfection; D019076:Transgenes; D000099209:Sodium-Iodide Symporters
chemical_list: D015500:Chloramphenicol O-Acetyltransferase; D011108:Polymers; D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: Gene therapy; Lungs; Molecular imaging; Nonviral vector; Tetrafunctional block copolymers