6533b7d4fe1ef96bd1261d22

RESEARCH PRODUCT

Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid‐like nanoparticles resolves liver fibrosis

subject

description

Fibrosis accompanies the wound-healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I that often progresses to cirrhosis. Here we present ample in-vivo evidence of an up to 90% suppression of procollagen α1(I) expression, a reduction of septa formation and a 40–60% decrease of collagen deposition in mice with progressive and advanced liver fibrosis, that received cationic lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene (LNP-siCol1a1). After intravenous injection up to ninety percent of LNP-siCol1a1 were retained in the liver of fibrotic mice and accumulated in nonparenchymal > parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis. Conclusion The data reported in the present study extensively show that LNP-siCol1a1 specifically reduce total hepatic collagen content without detectable side effects, potentially qualifying as a therapy for fibrotic liver diseases.