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

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.