Development and characterization of non-viral vectors based on cationic niosomes to address cystic fibrosis disease by gene therapy approach
- Autores: Myriam Sainz Ramos
- Directores de la Tesis: Gustavo Puras Ochoa (dir. tes.), José Luis Pedraz Muñoz (dir. tes.)
- Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2022
- Idioma: inglés
- Tribunal Calificador de la Tesis: Antonio José Leitâo das Neves Almeida (presid.), Jon Zarate Sesma (secret.), Lluís Montoliu i José (voc.), Laura Saenz del Burgo Martínez (voc.), Cristina Soto-Sánchez (voc.)
- Programa de doctorado: Programa de Doctorado en Investigación y Evaluación de Medicamentos. Aplicación de la Tecnología Farmacéutica al Desarrollo de Terapias Avanzadas por la Universidad del País Vasco/Euskal Herriko Unibertsitatea
- Materias:
- Enlaces
- Tesis en acceso abierto en: ADDI
- Resumen
Gene therapy is based on the delivery of exogenous genetic material into target cells to modulate theexpression of an altered genome in order to treat a specific disease. Lipid nanocarriers, such as niosomesbased on cationic lipids, non-ionic surfactants and ¿helper¿ components, are considered attractivecandidate for non-viral vectors due to their suitable biocompatibility and high versatility. The niosomechemical composition and their elaboration method influence the biophysical properties which have animpact on transfection efficiency and cytotoxicity. Indeed, compounds with specific properties have beenincluded to overcome some disadvantages of niosome formulations, such as chloroquine, which promotesendosomal escape. Gene therapy can be an excellent treatment for many disorders, in particular cysticfibrosis that is an autosomal monogenic recessive disease caused by different mutations in the cysticfibrosis conductance regulator (CFTR) gene. In this doctoral thesis, we focused on the development andin-depth biophysical and biological characterization of non-viral vectors based on cationic niosomes toface cystic fibrosis by gene therapy approach. The data obtained support that the inclusion of thechloroquine molecule in niosome formulations improves the biophysical properties of niosomes withenhanced transfection efficiencies and lower cytotoxicity. In addition, these niosomes are able to increasethe production of functional CFTR protein in cystic fibrosis cells. Furthermore, the development of athree-dimensional scaffold that better mimics the in vivo environment showed utility for evaluating newtreatments and different schedules of administration for cystic fibrosis.
