TY - JOUR
T1 - Gene therapy strategies for idiopathic pulmonary fibrosis
T2 - recent advances, current challenges, and future directions
AU - Ruigrok, Mitchel J.R.
AU - Frijlink, Henderik W.
AU - Melgert, Barbro N.
AU - Olinga, Peter
AU - Hinrichs, Wouter L.J.
N1 - © 2021 The Author(s).
PY - 2021/3/12
Y1 - 2021/3/12
N2 - Idiopathic pulmonary fibrosis (IPF) is a chronic disease in which the lungs become irreversibly scarred, leading to declining lung function. As currently available drugs do not cure IPF, there remains a great medical need for more effective treatments. Perhaps this need could be addressed by gene therapies, which offer powerful and versatile ways to attenuate a wide range of processes involved in fibrosis. Despite the potential benefits of gene therapy, no one has reviewed the current state of knowledge regarding its application for treating IPF. We therefore analyzed publications that reported the use of gene therapies to treat pulmonary fibrosis in animals, as clinical studies have not been published yet. In this review, we first provide an introduction on the pathophysiology of IPF and the most well-established gene therapy approaches. We then present a comprehensive evaluation of published animal studies, after which we provide recommendations for future research to address challenges with respect to the selection and use of animal models as well as the development of delivery vectors and dosage forms. Addressing these considerations will bring gene therapies one step closer to clinical testing and thus closer to patients.
AB - Idiopathic pulmonary fibrosis (IPF) is a chronic disease in which the lungs become irreversibly scarred, leading to declining lung function. As currently available drugs do not cure IPF, there remains a great medical need for more effective treatments. Perhaps this need could be addressed by gene therapies, which offer powerful and versatile ways to attenuate a wide range of processes involved in fibrosis. Despite the potential benefits of gene therapy, no one has reviewed the current state of knowledge regarding its application for treating IPF. We therefore analyzed publications that reported the use of gene therapies to treat pulmonary fibrosis in animals, as clinical studies have not been published yet. In this review, we first provide an introduction on the pathophysiology of IPF and the most well-established gene therapy approaches. We then present a comprehensive evaluation of published animal studies, after which we provide recommendations for future research to address challenges with respect to the selection and use of animal models as well as the development of delivery vectors and dosage forms. Addressing these considerations will bring gene therapies one step closer to clinical testing and thus closer to patients.
KW - INDUCED LUNG FIBROSIS
KW - PLASMINOGEN-ACTIVATOR INHIBITOR-1
KW - WNT/BETA-CATENIN PATHWAY
KW - EXTRACELLULAR-MATRIX
KW - MYOFIBROBLAST ACTIVATION
KW - FIBROGENIC RESPONSES
KW - INTERFERING RNA
KW - ANIMAL-MODELS
KW - BLEOMYCIN
KW - MECHANISMS
U2 - 10.1016/j.omtm.2021.01.003
DO - 10.1016/j.omtm.2021.01.003
M3 - Review article
C2 - 33614824
VL - 20
SP - 483
EP - 496
JO - Molecular Therapy - Methods & Clinical Development
JF - Molecular Therapy - Methods & Clinical Development
ER -