Targeted DNA triplex-forming oligonucleotide liposome for pulmonary fibrosis gene therapy.

Pulmonary fibrosis is a refractory and serious disease, and there is a need for developing effective clinical treatment strategies. A major cause of pulmonary fibrosis is excessive deposition of extracellular matrix, while the overexpression of plasminogen activator inhibitor 1 (PAI-1) is one of the key drivers of the excessive deposition. Here, we report a targeted DNA triplex-forming oligonucleotide (TFO) liposome (tLipo-TFO1) for pulmonary fibrosis gene therapy to accelerate the clearance of deposited extracellular matrix. tLipo-TFO1 can block the expression of the Serpine1 gene of pulmonary fibrotic cells and thereby downregulate the function of Serpine1-gene-encoded PAI-1 protein. Functional assessments show pulmonary fibrosis-targeting, fibrinolysis-activating effect, as well as significant efficacy in treating pulmonary-fibrosis-bearing mice in vivo. Our study thus suggests that this targeted DNA TFO liposome could be a gene therapy approach for pulmonary fibrosis.