Targeted RNA interference for hepatic fibrosis

Expert Opinion on Biological Therapy

Volumn 9, Issue 10, 2009, Pages 1305-1312

  Hu, Ping Fang ^a   Xie, Wei Fen ^a  

^a SECOND MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

Hepatic fibrosis; Hepatic stellate cell (HSC); Hepatocyte; RNA interference (RNAi); Small interfering RNA (siRNA); Targeted therapy

Indexed keywords

1,2 DIOLEOYL 3 TRIMETHYLAMMONIOPROPANE; ALPHA FETOPROTEIN; APOLIPOPROTEIN A1; CASPASE 8; COMPLEMENTARY DNA; CONNECTIVE TISSUE GROWTH FACTOR; DIMETHYLNITROSAMINE; DOXORUBICIN; FAS ANTIGEN; GLIAL FIBRILLARY ACIDIC PROTEIN; GLIOTOXIN; GREEN FLUORESCENT PROTEIN; HUMAN SERUM ALBUMIN; IMMUNOGLOBULIN F(AB) FRAGMENT; LIPOSOME; MANNOSE 6 PHOSPHATE; MESSENGER RNA; N ACETYLGALACTOSAMINE; PLASMID DNA; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; RETINOL; SCATTER FACTOR; SMALL INTERFERING RNA; SOMATOMEDIN B; SYNAPTOPHYSIN;

ADENOVIRUS; CELL SPECIFICITY; CYTOMEGALOVIRUS; DRUG DISTRIBUTION; DRUG FORMULATION; DRUG TARGETING; GENE DELIVERY SYSTEM; GENE TARGETING; GENE THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYDRODYNAMICS; LIPOSOMAL GENE DELIVERY SYSTEM; LIVER CELL; LIVER FIBROSIS; LOXP SITE; NONHUMAN; POSTTRANSCRIPTIONAL GENE SILENCING; REVIEW; RNA INTERFERENCE; VIRAL GENE DELIVERY SYSTEM;

GENE SILENCING; GENE THERAPY; HUMANS; LIVER CIRRHOSIS; RNA INTERFERENCE;

EID: 70349397623     PISSN: 14712598     EISSN: None     Source Type: Journal    
DOI: 10.1517/14712590903213677     Document Type: Review

References (78)

1. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000;275:2247-2250
2. Friedman SL. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008;134:1655-1669
3. Benyon RC, Iredale JP. Is liver fibrosis reversible? Gut 2000;46:443-446
4. Friedman SL. Hepatic fibrosis - overview. Toxicology 2008;254:120-129
5. Fallowfield JA, Iredale JP. Targeted treatments for cirrhosis. Expert Opin Ther Targets 2004;8:423-435
6. Stevenson M. Therapeutic potential of RNA interference. N Engl J Med 2004;351:1772-1777
7. Scherer LJ, Rossi JJ. Approaches for the sequence-specific knockdown of mRNA. Nat Biotechnol 2003;21:1457-1465
8. Aagaard L, Rossi JJ. RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev 2007;59:75-86 (Pubitemid 46770900)
9. Hannon GJ, Rossi JJ. Unlocking the potential of the human genome with RNA interference. Nature 2004;431:371-378 (Pubitemid 39265678)
10. Chen SW, Zhang XR, Wang CZ, etal. RNA interference targeting the platelet-derived growth factor receptor β subunit ameliorates experimental hepatic fibrosis in rats. Liver Int 2008;28:1446-1457
11. George J, Tsutsumi M. siRNA-mediated knockdown of connective tissue growth factor prevents N-nitrosodimethylamine-induced hepatic fibrosis in rats. Gene Ther 2007;14:790-803 (Pubitemid 46706059)
12. Kim KH, Kim HC, Hwang MY, et al. The antifibrotic effect of TGF-β1 siRNAs in murine model of liver cirrhosis. Biochem Biophys Res Commun 2006;343:1072-1078
13. Sato Y, Murase K, Kato J, et al. Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol 2008;26:431-42 •• The first study, to our knowledge, in which siRNA was delivered to HSCs in vivo using an elegant vitamin A-coupled liposomal delivery system, and targeted the collagen-specific chaperone molecule (gp46) to treat liver fibrosis.
14. Hu YB, Li DG, Lu HM. Modified synthetic siRNA targeting tissue inhibitor of metalloproteinase-2 inhibits hepatic fibrogenesis in rats. J Gene Med 2007;9:217-229
15. Oliveira S, Storm G, Schiffelers RM. Targeted delivery of siRNA. J Biomed Biotechnol 2006;2006:63675
16. Kawakami S, Hashida M. Targeted delivery systems of small interfering RNA by systemic administration. Drug Metab Pharmacokinet 2007;22:142-151
17. Juliano R, Alam MR, Dixit V, Kang H. Mechanisms and strategies for effective delivery of antisense and siRNA oligonucleotides. Nucleic Acids Res 2008;36:4158-4171 (Pubitemid 351984831)
18. Santel A, Aleku M, Keil O, et al. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther 2006;13:1222-1234 (Pubitemid 44184716)
19. Herweijer H, Wolff JA. Gene therapy progress and prospects: hydrodynamic gene delivery. Gene Ther 2007;14:99-107 (Pubitemid 46043816)
20. Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Ther 1999;6:1258-1266 (Pubitemid 29359019)
21. Yang J, Chen S, Huang L, et al. Sustained expression of naked plasmid DNA encoding hepatocyte growth factor in mice promotes liver and overall body growth. Hepatology 2001;33:848-859 (Pubitemid 32246634)
22. Mei S, Wang X, Zhang J, etal. Invivo transfection of C/EBP-α gene could ameliorate CCL4-induced hepatic fibrosis in mice. Hepatol Res 2007;37:531-539
23. Sebestyen MG, Budker VG, Budker T, et al. Mechanism of plasmid delivery by hydrodynamic tail vein injection. I. Hepatocyte uptake of various molecules. J Gene Med 2006;8:852-873
24. Song E, Lee SK, Wang J, etal. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med 2003;9:347-51 •• This study delivered chemically synthesizd siRNA against Fas to hepatocytes in vivo by HTV procedure and investigated the therapeutic effect of Fas siRNA on fulminant hepatitis and liver fibrosis in mice. (Pubitemid 36362792)
25. Zender L, Hutker S, Liedtke C, et al. Caspase 8 small interfering RNA prevents acute liver failure in mice. Proc Natl Acad Sci USA 2003;100:7797-7802 (Pubitemid 36760049)
26. Akhtar S, Benter IF. Nonviral delivery of synthetic siRNAs invivo. J Clin Invest 2007;117:3623-3632 (Pubitemid 350224068)
27. Li G, Xie Q, Shi Y, etal. Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats. J Gene Med 2006;8:889-900 (Pubitemid 44097143)
28. Van de Casteele M, Omasta A, Janssens S, etal. Invivo gene transfer of endothelial nitric oxide synthase decreases portal pressure in anaesthetised carbon tetrachloride cirrhotic rats. Gut 2002;51:440-445
29. Yu Q, Shao R, Qian HS, etal. Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension. J Clin Invest 2000;105:741-748 (Pubitemid 30164112)
30. Budker VG, Subbotin VM, Budker T, et al. Mechanism of plasmid delivery by hydrodynamic tail vein injection. II. Morphological studies. J Gene Med 2006;8:874-888 (Pubitemid 44097142)
31. Sakai M, Nishikawa M, Thanaketpaisarn O, et al. Hepatocyte-targeted gene transfer by combination of vascularly delivered plasmid DNA and invivo electroporation. Gene Ther 2005;12:607-616 (Pubitemid 40468108)
32. Ogata I, Mochida S, Tomiya T, Fujiwara K. Minor contribution of hepatocytes to collagen production in normal and early fibrotic rat livers. Hepatology 1991;14:361-367
33. Zeisberg M, Yang C, Martino M, et al. Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J Biol Chem 2007;282:23337-23347 (Pubitemid 47311952)
34. Han C, Li G, Lim K, etal. Transgenic expression of cyclooxygenase-2 in hepatocytes accelerates endotoxin-induced acute liver failure. J Immunol 2008;181:8027-8035
35. Gkretsi V, Apte U, Mars WM, et al. Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly. Hepatology 2008;48:1932-1941
36. Sa Cunha A, Bonte E, Dubois S, et al. Inhibition of rat hepatocellular carcinoma tumor growth after multiple infusions of recombinant Ad.AFPtk followed by ganciclovir treatment. J Hepatol 2002;37:222-230 (Pubitemid 34833084)
37. Willhauck MJ, Sharif Samani BR, Klutz K, et al. α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma. Gene Ther 2008;15:214-223 (Pubitemid 351150044)
38. Diez S, Navarro G, de ICT. Invivo targeted gene delivery by cationic nanoparticles for treatment of hepatocellular carcinoma. J Gene Med 2009;11:38-45
39. Watanabe T, Umehara T, Yasui F, et al. Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome. J Hepatol 2007;47:744-750 (Pubitemid 350051113)
40. Fumoto S, Kawakami S, Ito Y, et al. Enhanced hepatocyte-selective invivo gene expression by stabilized galactosylated liposome/plasmid DNA complex using sodium chloride for complex formation. Mol Ther 2004;10:719-729 (Pubitemid 39272861)
41. Sato A, Takagi M, Shimamoto A, et al. Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 2007;28:1434-1442 (Pubitemid 44959042)
42. Schmitz V, Qian C, Ruiz J, etal. Gene therapy for liver diseases: recent strategies for treatment of viral hepatitis and liver malignancies. Gut 2002;50:130-135
43. Rozema DB, Lewis DL, Wakefield DH, et al. Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes. Proc Natl Acad Sci USA 2007;104:12982-12987 •• An excellent study evaluated targeted delivery of siRNA to hepatocytes both invitro and invivo using a siRNA Dynamic PolyConjugates, in which the hepatocytes targeting ligand N-acetylgalactosamine (NAG) was used.
44. Kim SI, Shin D, Choi TH, etal. Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. Mol Ther 2007;15:1145-1152
45. Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008;88:125-172
46. Bataller R, Brenner DA. Hepatic stellate cells as a target for the treatment of liver fibrosis. Semin Liver Dis 2001;21:437-451 (Pubitemid 32923771)
47. de Bleser PJ, Jannes P, van Buul-Offers SC, et al. Insulin like growth factor-II/mannose 6-phosphate receptor is expressed on CCl4-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-β in cocultures with sinusoidal endothelial cells. Hepatology 1995;21:1429-1437
48. Beljaars L, Molema G, Weert B, et al. Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells. Hepatology 1999;29:1486-1493 (Pubitemid 29211051)
49. Greupink R, Bakker HI, van Goor H, et al. Mannose-6-phosphate/insulin- like growth factor-II receptors may represent a target for the selective delivery of mycophenolic acid to fibrogenic cells. Pharm Res 2006;23:1827-1834 (Pubitemid 44200546)
50. Greupink R, Bakker HI, Bouma W, et al. The antiproliferative drug doxorubicin inhibits liver fibrosis in bile duct-ligated rats and can be selectively delivered to hepatic stellate cells invivo. J Pharmacol Exp Ther 2006;317:514-521
51. Gonzalo T, Beljaars L, van de Bovenkamp M, et al. Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells. J Pharmacol Exp Ther 2007;321:856-865 (Pubitemid 46762697)
52. Beljaars L, Molema G, Schuppan D, et al. Successful targeting to rat hepatic stellate cells using albumin modified with cyclic peptides that recognize the collagen type VI receptor. J Biol Chem 2000;275:12743-12751 (Pubitemid 30241427)
53. Friedman SL. Targeting siRNA to arrest fibrosis. Nat Biotechnol 2008;26:399-400
54. Cassiman D, van Pelt J, De Vos R, et al. Synaptophysin: a novel marker for human and rat hepatic stellate cells. Am J Pathol 1999;155:1831-1839
55. Magness ST, Bataller R, Yang L, Brenner DA. A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations. Hepatology 2004;40:1151-1159 (Pubitemid 39425571)
56. Elrick LJ, Leel V, Blaylock MG, et al. Generation of a monoclonal human single chain antibody fragment to hepatic stellate cells-a potential mechanism for targeting liver anti-fibrotic therapeutics. J Hepatol 2005;42:888-896 (Pubitemid 40693206)
57. Orr JG, Leel V, Cameron GA, et al. Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells. Hepatology 2004;40:232-242 (Pubitemid 38868942)
58. Douglass A, Wallace K, Parr R, et al. Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury. J Hepatol 2008;49:88-98
59. Song E, Zhu P, Lee SK, etal. Antibody mediated invivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 2005;23:709-717 • This study reported for the first time, to our knowledge, that a protamine-antibody fusion protein could be used as a vehicle for receptor-directed delivery of siRNA.
60. Herrmann J, Arias M, Van De Leur E, et al. CSRP2, TIMP-1, and SM22α promoter fragments direct hepatic stellate cell-specific transgene expression invitro, but not invivo. Liver Int 2004;24:69-79 (Pubitemid 38351216)
61. Inagaki Y, Kushida M, Higashi K, et al. Cell type-specific intervention of transforming growth factor β/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice. Gastroenterology 2005;129:259-268 (Pubitemid 41002059)
62. Kinoshita K, Iimuro Y, Fujimoto J, et al. Targeted and regulable expression of transgenes in hepatic stellate cells and myofibroblasts in culture and invivo using an adenoviral Cre/loxP system to antagonise hepatic fibrosis. Gut 2007;56:396-404 • An important study validated a new concept of gene therapy for hepatic fibrosis using the Cre/loxP system and a cell-specific collagen promoter. (Pubitemid 46579772)
63. Dahl D. The vimentin-GFA protein transition in rat neuroglia cytoskeleton occurs at the time of myelination. J Neurosci Res 1981;6:741-748 (Pubitemid 12179762)
64. Brenner M, Kisseberth WC, Su Y, et al. GFAP promoter directs astrocyte-specific expression in transgenic mice. J Neurosci 1994;14:1030-1037 (Pubitemid 24081901)
65. Cassiman D, Libbrecht L, Desmet V, et al. Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J Hepatol 2002;36:200-209 (Pubitemid 34146426)
66. Gard AL, White FP, Dutton GR. Extra-neural glial fibrillary acidic protein (GFAP) immunoreactivity in perisinusoidal stellate cells of rat liver. J Neuroimmunol 1985;8:359-375
67. Chen SW, Chen YX, Zhang XR, et al. Targeted inhibition of platelet-derived growth factor receptor-β subunit in hepatic stellate cells ameliorates hepatic fibrosis in rats. Gene Ther 2008;15:1424-1435 •• The first study demonstrated that GFAP promoter could drive the expression of siRNA selectively in HSCs in liver.
68. Lin Y, Xie WF, Chen YX, etal. Treatment of experimental hepatic fibrosis by combinational delivery of urokinase-type plasminogen activator and hepatocyte growth factor genes. Liver Int 2005;25:796-807
69. St George JA. Gene therapy progress and prospects: adenoviral vectors. Gene Ther 2003;10:1135-1141 (Pubitemid 36896588)
70. Wang X, Huang G, Mei S, et al. Over-expression of C/EBP-α induces apoptosis in cultured rat hepatic stellate cells depending on p53 and peroxisome proliferator-activated receptor-γ. Biochem Biophys Res Commun 2009;380:286-291
71. Lavina B, Gracia-Sancho J, Rodriguez-Vilarrupla A, etal. Superoxide dismutase gene transfer reduces portal pressure in CCl4 cirrhotic rats with portal hypertension. Gut 2009;58:118-125
72. Taura K, De Minicis S, Seki E, et al. Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis. Gastroenterology 2008;135:1729-1738
73. Camino AM, Atorrasagasti C, Maccio D, et al. Adenovirus-mediated inhibition of SPARC attenuates liver fibrosis in rats. J Gene Med 2008;10:993-1004
74. Nakatani T, Kuriyama S, Tominaga K, et al. Assessment of efficiency and safety of adenovirus mediated gene transfer into normal and damaged murine livers. Gut 2000;47:563-570
75. Narvaiza I, Aparicio O, Vera M, et al. Effect of adenovirus-mediated RNA interference on endogenous microRNAs in a mouse model of multidrug resistance protein 2 gene silencing. J Virol 2006;80:12236-12247 (Pubitemid 44904374)
76. Hu PF, Chen H, Zhong W, et al. Adenovirus-mediated transfer of siRNA against PAI-1 mRNA ameliorates hepatic fibrosis in rats. J Hepatol 2009;51:102-113
77. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998;391:806-811 (Pubitemid 28099681)
78. Dorsett Y, Tuschl T. siRNAs: applications in functional genomics and potential as therapeutics. Nat Rev Drug Discov 2004;3:318-329 (Pubitemid 38499759)