Abstract
Prognosis of patients with cystic fibrosis (CF) varies extensively despite recent advances in targeted therapies that improve CF transmembrane conductance regulator (CFTR) function. Despite being a multi-organ disease, extensive lung tissue destruction remains the major cause of morbidity and mortality. Progress towards a curative treatment strategy that implements a CFTR gene addition-technology to the patients’ lungs has been slow and not yet developed beyond clinical trials. Improved delivery vectors are needed to overcome the body’s defense system and ensure an efficient and consistent clinical response before gene therapy is suitable for clinical care. Cell-based therapy–which relies on functional modification of allogenic or autologous cells ex vivo, prior to transplantation into the patient–is now a therapeutic reality for various diseases. For CF, pioneering research has demonstrated proof-of-principle for allogenic transplantation of cultured human airway stem cells into mouse airways. However, applying a cell-based therapy to the human airways has distinct challenges. We review CF gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies. Progress towards identification, correction, and expansion of a suitable regenerative cell, as well as refinement of pre-cell transplant lung conditioning protocols is discussed.
Highlights
Reviewed by: Susan Reynolds, Nationwide Children’s Hospital, Columbus, United States Massimo Conese, University of Foggia, Italy
We review cystic fibrosis (CF) gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies
A successful gene therapy system for restoration of cystic fibrosis transmembrane conductance regulator (CFTR) function needs to navigate the complexities of the lung clearance and innate immunity defense functions that are further complicated in the CF airways due to increased mucus volume and viscosity (reviewed in (Donnelley and Parsons 2018))
Summary
Prognosis of patients with cystic fibrosis (CF) varies extensively despite recent advances in targeted therapies that improve CF transmembrane conductance regulator (CFTR) function. Progress towards a curative treatment strategy that implements a CFTR gene addition-technology to the patients’ lungs has been slow and not yet developed beyond clinical trials. Cell-based therapy–which relies on functional modification of allogenic or autologous cells ex vivo, prior to transplantation into the patient–is a therapeutic reality for various diseases. We review CF gene therapies using viral and non-viral delivery strategies and discuss current advances towards autologous cell-based therapies. Correction, and expansion of a suitable regenerative cell, as well as refinement of pre-cell transplant lung conditioning protocols is discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
