Treating Pulmonary Fibrosis with Non-Viral Gene Therapy: From Bench to Bedside

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by irreversible lung scarring, which achieves almost 80% five-year mortality rate. Undeniably, commercially available pharmaceuticals, such as pirfenidone and nintedanib, exhibit certain effects on improving the well-being of IPF patients, but the stubbornly high mortality still indicates a great urgency of developing superior therapeutics against this devastating disease. As an emerging strategy, gene therapy brings hope for the treatment of IPF by precisely regulating the expression of specific genes. However, traditional administration approaches based on viruses severely restrict the clinical application of gene therapy. Nowadays, non-viral vectors are raised as potential strategies for in vivo gene delivery, attributed to their low immunogenicity and excellent biocompatibility. Herein, we highlight a variety of non-viral vectors, such as liposomes, polymers, and proteins/peptides, which are employed in the treatment of IPF. By respectively clarifying the strengths and weaknesses of the above candidates, we would like to summarize the requisite features of vectors for PF gene therapy and provide novel perspectives on design-decisions of the subsequent vectors, hoping to accelerate the bench-to-bedside pace of non-viral gene therapy for IPF in clinical setting.

circGRHPR inhibits aberrant epithelial-mesenchymal transformation progression of lung epithelial cells associated with idiopathic pulmonary fibrosis

“…IPF is characterized by a tumor-like disease and exhibits an extremely unfavorable prognosis. After the diagnosis of IPF, the median survival period of the patient is only less than 3 years, with approximately 80% mortality rate within 5 years (Huang et al 2022 ). Meanwhile, the incidence rate of IPF is increasing, and at least 3 million people around the world are facing serious risks of this disease (Cheng et al 2022 ).…”

Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation via repressing M2 macrophage production

“…It is noted that the liposome delivery system, due to its high degree of biocompatibility, has been widely employed to enhance the efficiency of drug delivery, especially in siRNA delivery ( 9 ). However, clinical applications of siRNA-based therapeutics have been limited by nucleases, rapid renal clearance and poor cellular uptake due to negatively charged cell membranes following systemic administration ( 9 , 10 ). Nevertheless, cationic liposomes, consisting of an amphiphilic phospholipid bilayer, could efficiently load the siRNA with its positive electricity ( 9 , 10 ).…”

“…However, clinical applications of siRNA-based therapeutics have been limited by nucleases, rapid renal clearance and poor cellular uptake due to negatively charged cell membranes following systemic administration ( 9 , 10 ). Nevertheless, cationic liposomes, consisting of an amphiphilic phospholipid bilayer, could efficiently load the siRNA with its positive electricity ( 9 , 10 ). Indeed, the cationic liposomes loaded with siRNAs were well studied in Kaposi’s sarcoma ( 11 ), ovarian cancer ( 12 ), cystic fibrosis ( 13 ) and lung squamous cell carcinoma ( 14 ).…”