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

Carolina Jiménez Calvente, Alfica Sehgal, Yury Popov, Yong Ook Kim, Victor F Zevallos, Ugur Sahin, Mustafa Diken, Detlef Schuppan

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

UNLABELLED: Fibrosis accompanies the wound-healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I. Fibrosis often progresses to cirrhosis. Here we present 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. After intravenous injection, up to 90% of lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene were retained in the liver of fibrotic mice and accumulated in nonparenchymal more than parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis.

CONCLUSION: Our lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene specifically reduce total hepatic collagen content without detectable side effects, potentially qualifying as a therapy for fibrotic liver diseases.

Original languageEnglish
Pages (from-to)1285-1297
Number of pages13
JournalHepatology
Volume62
Issue number4
Early online date10 Jun 2015
DOIs
Publication statusPublished - 1 Oct 2015
Externally publishedYes

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