title: Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid-like nanoparticles resolves liver fibrosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany.|Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.
authors.forename: Carolina
authors.initials: C
authors.lastname: Jiménez Calvente
authors.affiliation: Alnylam Pharmaceuticals, Cambridge, MA.
authors.forename: Alfica
authors.initials: A
authors.lastname: Sehgal
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Yury
authors.initials: Y
authors.lastname: Popov
authors.affiliation: Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany.|Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.
authors.forename: Yong Ook
authors.initials: YO
authors.lastname: Kim
authors.affiliation: Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany.|Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Zevallos
authors.affiliation: Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.|Center of Translational Oncology, Mainz, Germany.
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
authors.affiliation: Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.|Center of Translational Oncology, Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany.|Research Center for Immunotherapy, University of Mainz Medical Center, Mainz, Germany.|Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D016503:Drug Delivery Systems; D008103:Liver Cirrhosis / Q000235:genetics / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D000067492:RNAi Therapeutics
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D034741:RNA, Small Interfering