Luis Sendra1, Daniel Pérez2, Antonio Miguel1, María José Herrero3,4, Inmaculada Noguera5, Ana Díaz5, Domingo Barettino6, Luis Martí-Bonmatí2, Salvador F Aliño1,7,8. 1. Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain. 2. Servicio de Radiología, Hospital Universitario y Politécnico La Fe, Grupo de Investigación Biomédica de Imagen IIS La Fe, Valencia, Spain. 3. Departamento de Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain. maria.jose.herrero@uv.es. 4. Unidad de Farmacogenética, IIS La Fe, Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Valencia, Spain. maria.jose.herrero@uv.es. 5. SCSIE, Servicio Central de Soporte a la Investigación Experimental, Universidad de Valencia, Valencia, Spain. 6. Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain. 7. Unidad de Farmacogenética, IIS La Fe, Servicio de Farmacia, Hospital Universitario y Politécnico La Fe, Valencia, Spain. 8. Unidad de Farmacología Clínica, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Abstract
OBJECTIVE: The efficiency of endovascular liver gene transfer in pigs is evaluated by comparing two models of retrograde catheterization: single lobe catheterization with portal inflow (open procedure) versus whole liver isolation with portal and inferior vena cava blockage (close procedure). METHODS: Percutaneous endovascular catheterization was performed in pigs. Open procedure (n = 3): 8Fr balloon catheter placement in a suprahepatic branch through the jugular vein. Closed procedure (n = 3): simultaneous catheterization of the intrahepatic portal vein (transhepatic catheterization, 10Fr balloon catheter), the supra- and infrahepatic cava veins (8Fr balloon catheters through the jugular and femoral veins). In both models, 200 ml of hAAT DNA solution (20 μg/ml) were retrogradely injected at 20 ml/s. Tissue samples (8 per liver) were obtained 14 days later and the exogenous DNA, RNA and protein per cell were quantified. Blood samples were collected periodically for transaminase determination in all the animals. RESULTS: The open procedure achieved lower (approx. 1000-fold) DNA delivery, resulting in a significantly lower (p < 0.001) gene transcription (> 100-fold). The closed model also achieved a higher translation index, although differences were smaller (p < 0.001). CONCLUSIONS: Portal inflow blockage increased the delivery, transcription and translation indexes, significantly improving the final procedure efficacy when compared with an open procedure. KEY POINTS: Endovascular hydrodynamic pig liver gene transfer: open procedure versus closed procedure. Open procedure resulted in much lower DNA delivery than closed model. Open procedure reached significantly lower gene transcription index. Translation index with closed model was higher than with the open.
OBJECTIVE: The efficiency of endovascular liver gene transfer in pigs is evaluated by comparing two models of retrograde catheterization: single lobe catheterization with portal inflow (open procedure) versus whole liver isolation with portal and inferior vena cava blockage (close procedure). METHODS: Percutaneous endovascular catheterization was performed in pigs. Open procedure (n = 3): 8Fr balloon catheter placement in a suprahepatic branch through the jugular vein. Closed procedure (n = 3): simultaneous catheterization of the intrahepatic portal vein (transhepatic catheterization, 10Fr balloon catheter), the supra- and infrahepatic cava veins (8Fr balloon catheters through the jugular and femoral veins). In both models, 200 ml of hAAT DNA solution (20 μg/ml) were retrogradely injected at 20 ml/s. Tissue samples (8 per liver) were obtained 14 days later and the exogenous DNA, RNA and protein per cell were quantified. Blood samples were collected periodically for transaminase determination in all the animals. RESULTS: The open procedure achieved lower (approx. 1000-fold) DNA delivery, resulting in a significantly lower (p < 0.001) gene transcription (> 100-fold). The closed model also achieved a higher translation index, although differences were smaller (p < 0.001). CONCLUSIONS: Portal inflow blockage increased the delivery, transcription and translation indexes, significantly improving the final procedure efficacy when compared with an open procedure. KEY POINTS: Endovascular hydrodynamic pig liver gene transfer: open procedure versus closed procedure. Open procedure resulted in much lower DNA delivery than closed model. Open procedure reached significantly lower gene transcription index. Translation index with closed model was higher than with the open.
Authors: Elena L Aronovich; Kendra A Hyland; Bryan C Hall; Jason B Bell; Erik R Olson; Myra Urness Rusten; David W Hunter; N Matthew Ellinwood; R Scott McIvor; Perry B Hackett Journal: Hum Gene Ther Date: 2017-05-19 Impact factor: 5.695
Authors: Luis Sendra; María José Herrero; Eva María Montalvá; Inmaculada Noguera; Francisco Orbis; Ana Díaz; Rafael Fernández-Delgado; Rafael López-Andújar; Salvador F Aliño Journal: PLoS One Date: 2019-11-05 Impact factor: 3.240
Authors: Tatjana Chan; Hiu Man Grisch-Chan; Philipp Schmierer; Ulrike Subotic; Nicole Rimann; Tanja Scherer; Udo Hetzel; Matthias Bozza; Richard Harbottle; James A Williams; Barbara Steblaj; Simone K Ringer; Johannes Häberle; Xaver Sidler; Beat Thöny Journal: Mol Ther Methods Clin Dev Date: 2022-01-19 Impact factor: 6.698
Authors: Luis Sendra; Antonio Miguel; Daniel Pérez-Enguix; María José Herrero; Eva Montalvá; María Adelaida García-Gimeno; Inmaculada Noguera; Ana Díaz; Judith Pérez; Pascual Sanz; Rafael López-Andújar; Luis Martí-Bonmatí; Salvador F Aliño Journal: PLoS One Date: 2016-10-03 Impact factor: 3.240