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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2015

Open Access 01-12-2015 | Review

Fighting against kidney diseases with small interfering RNA: opportunities and challenges

Authors: Cheng Yang, Chao Zhang, Zitong Zhao, Tongyu Zhu, Bin Yang

Published in: Journal of Translational Medicine | Issue 1/2015

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Abstract

The significant improvements in siRNA therapy have been achieved, which have great potential applications in humans. The kidney is a comparatively easy target organ of siRNA therapy due to its unique structural and functional characteristics. Here, we reviewed recent achievements in siRNA design, delivery and application with focuses on kidney diseases, in particular kidney transplant-related injuries. In addition, the strategy for increasing serum stability and immune tolerance of siRNA was also discussed. At last, the future challenges of siRNA therapy including organ/tissue/cell-specific delivery and time-controlled silence, as well as selecting therapeutic targets, were addressed as well.
Literature
1.
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998;391:806–11.CrossRefPubMed
2.
Brosnan CA, Voinnet O. Cell-to-cell and long-distance siRNA movement in plants: mechanisms and biological implications. Curr Opin Plant Biol. 2011;14:580–7.CrossRefPubMed
3.
4.
5.
Doi N, Zenno S, Ueda R, Ohki-Hamazaki H, Ui-Tei K, Saigo K. Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Curr Biol. 2003;13:41–6.CrossRefPubMed
6.
Hammond SM, Bernstein E, Beach D, Hannon GJ. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000;404:293–6.CrossRefPubMed
7.
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001;411:494–8.CrossRefPubMed
8.
Wang Z, Rao DD, Senzer N, Nemunaitis J. RNA interference and cancer therapy. Pharm Res. 2011;28:2983–95.CrossRefPubMed
9.
Petrocca F, Lieberman J. Promise and challenge of RNA interference-based therapy for cancer. J Clin Oncol. 2011;29:747–54.CrossRefPubMed
10.
Jeker LT, Bluestone JA. Small RNA regulators of T cell-mediated autoimmunity. J Clin Immunol. 2010;30:347–57.CrossRefPubMed
11.
Kowalski PS, Leus NG, Scherphof GL, Ruiters MH, Kamps JA, Molema G. Targeted siRNA delivery to diseased microvascular endothelial cells: cellular and molecular concepts. IUBMB Life. 2011;63:648–58.CrossRefPubMed
12.
Latronico MV, Condorelli G. RNA silencing: small RNA-mediated posttranscriptional regulation of mRNA and the implications for heart electropathophysiology. J Cardiovasc Electrophysiol. 2009;20:230–7.CrossRefPubMed
13.
14.
Yang C, Jia Y, Zhao T, Xue Y, Zhao Z, Zhang J, et al. Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys. J Surg Res. 2013;181:342–54.CrossRefPubMed
15.
Racz Z, Hamar P. RNA interference in research and therapy of renal diseases. Contrib Nephrol. 2008;159:78–95.PubMed
16.
Chaudhary A, Srivastava S, Garg S. Development of a software tool and criteria evaluation for efficient design of small interfering RNA. Biochem Biophys Res Commun. 2011;404:313–20.CrossRefPubMed
17.
Elmen J, Thonberg H, Ljungberg K, Frieden M, Westergaard M, Xu Y, et al. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res. 2005;33:439–47.CrossRefPubMedCentralPubMed
18.
Yang C, Zhao T, Zhao Z, Jia Y, Li L, Zhang Y, et al. Serum-stabilized naked caspase-3 siRNA protects autotransplant kidneys in a porcine model. Mol Ther. 2014;22:1817–28.CrossRefPubMed
19.
Mook OR, Baas F, de Wissel MB, Fluiter K. Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. Mol Cancer Ther. 2007;6:833–43.CrossRefPubMed
20.
Kanasty R, Dorkin JR, Vegas A, Anderson D. Delivery materials for siRNA therapeutics. Nat Mater. 2013;12:967–77.CrossRefPubMed
21.
Deng Y, Wang CC, Choy KW, Du Q, Chen J, Wang Q, et al. Therapeutic potentials of gene silencing by RNA interference: principles, challenges, and new strategies. Gene. 2014;538:217–27.CrossRefPubMed
22.
Yang B, Hosgood SA, Nicholson ML. Naked small interfering RNA of caspase-3 in preservation solution and autologous blood perfusate protects isolated ischemic porcine kidneys. Transplantation. 2011;91:501–7.CrossRefPubMed
23.
Nam BY, Paeng J, Kim SH, Lee SH, Kim do H, Kang HY, et al. The MCP-1/CCR2 axis in podocytes is involved in apoptosis induced by diabetic conditions. Apoptosis. 2012;17:1–13.CrossRefPubMed
24.
Liu F, Ma XJ, Wang QZ, Zhao YY, Wu LN, Qin GJ. The effect of FoxO1 on the proliferation of rat mesangial cells under high glucose conditions. Nephrol Dial Transplant. 2014;29:1879–87.CrossRefPubMed
25.
Yang B, Elias JE, Bloxham M, Nicholson ML. Synthetic small interfering RNA down-regulates caspase-3 and affects apoptosis, IL-1 beta, and viability of porcine proximal tubular cells. J Cell Biochem. 2011;112:1337–47.CrossRefPubMed
26.
Takabatake Y, Isaka Y, Mizui M, Kawachi H, Shimizu F, Ito T, et al. Exploring RNA interference as a therapeutic strategy for renal disease. Gene Ther. 2005;12:965–73.CrossRefPubMed
27.
Wan X, Fan L, Hu B, Yang J, Li X, Chen X, et al. Small interfering RNA targeting IKKbeta prevents renal ischemia-reperfusion injury in rats. Am J Physiol Renal Physiol. 2011;300:F857–63.CrossRefPubMed
28.
Hamar P, Song E, Kokeny G, Chen A, Ouyang N, Lieberman J. Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2004;101:14883–8.CrossRefPubMedCentralPubMed
29.
Xia Z, Abe K, Furusu A, Miyazaki M, Obata Y, Tabata Y, et al. Suppression of renal tubulointerstitial fibrosis by small interfering RNA targeting heat shock protein 47. Am J Nephrol. 2008;28:34–46.CrossRefPubMed
30.
Cuevas S, Zhang Y, Yang Y, Escano C, Asico L, Jones JE, et al. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production. Hypertension. 2012;59:446–52.CrossRefPubMedCentralPubMed
31.
Gooding M, Browne LP, Quinteiro FM, Selwood DL. siRNA delivery: from lipids to cell-penetrating peptides and their mimics. Chem Biol Drug Des. 2012;80:787–809.CrossRefPubMed
32.
Amarzguioui M, Rossi JJ, Kim D. Approaches for chemically synthesized siRNA and vector-mediated RNAi. FEBS Lett. 2005;579:5974–81.CrossRefPubMed
33.
Braasch DA, Jensen S, Liu Y, Kaur K, Arar K, White MA, et al. RNA interference in mammalian cells by chemically-modified RNA. Biochemistry. 2003;42:7967–75.CrossRefPubMed
34.
35.
Gary DJ, Puri N, Won YY. Polymer-based siRNA delivery: perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery. J Control Release. 2007;121:64–73.CrossRefPubMed
36.
37.
Molitoris BA, Dagher PC, Sandoval RM, Campos SB, Ashush H, Fridman E, et al. siRNA targeted to p53 attenuates ischemic and cisplatin-induced acute kidney injury. J Am Soc Nephrol. 2009;20:1754–64.CrossRefPubMedCentralPubMed
38.
Zheng X, Zhang X, Sun H, Feng B, Li M, Chen G, et al. Protection of renal ischemia injury using combination gene silencing of complement 3 and caspase 3 genes. Transplantation. 2006;82:1781–6.CrossRefPubMed
39.
Himmelfarb J, Joannidis M, Molitoris B, Schietz M, Okusa MD, Warnock D, et al. Evaluation and initial management of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:962–7.CrossRefPubMedCentralPubMed
40.
Zhang D, Liu Y, Wei Q, Huo Y, Liu K, Liu F, et al. Tubular p53 regulates multiple genes to mediate AKI. J Am Soc Nephrol. 2014;25:2278–89.CrossRefPubMed
41.
Rabb H, O’Meara YM, Maderna P, Coleman P, Brady HR. Leukocytes, cell adhesion molecules and ischemic acute renal failure. Kidney Int. 1997;51:1463–8.CrossRefPubMed
42.
Sheridan AM, Bonventre JV. Cell biology and molecular mechanisms of injury in ischemic acute renal failure. Curr Opin Nephrol Hypertens. 2000;9:427–34.CrossRefPubMed
43.
44.
Tsapepas DS, Powell JT, Martin ST, Hardy MA, Ratner LE. An update to managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline. Clin Transplant. 2013;27:647–8.PubMed
45.
Powell JT, Tsapepas DS, Martin ST, Hardy MA, Ratner LE. Managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline. Clin Transplant. 2013;27:484–91.CrossRefPubMed
46.
Fujino T, Muhib S, Sato N, Hasebe N. Silencing of p53 RNA through transarterial delivery ameliorates renal tubular injury and downregulates GSK-3beta expression after ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2013;305:F1617–27.CrossRefPubMed
47.
Peng J, Li X, Zhang D, Chen JK, Su Y, Smith SB, et al. Hyperglycemia, p53, and mitochondrial pathway of apoptosis are involved in the susceptibility of diabetic models to ischemic acute kidney injury. Kidney Int. 2015;87:137–50.CrossRefPubMed
48.
Liu L, Li Y, Hu Z, Su J, Huo Y, Tan B, et al. Small interfering RNA targeting Toll-like receptor 9 protects mice against polymicrobial septic acute kidney injury. Nephron Exp Nephrol. 2012;122:51–61.CrossRefPubMed
49.
Shimizu H, Hori Y, Kaname S, Yamada K, Nishiyama N, Matsumoto S, et al. siRNA-based therapy ameliorates glomerulonephritis. J Am Soc Nephrol. 2010;21:622–33.CrossRefPubMedCentralPubMed
50.
51.
Ronkainen H, Vaarala MH, Hirvikoski P, Ristimaki A. HuR expression is a marker of poor prognosis in renal cell carcinoma. Tumour Biol. 2011;32:481–7.CrossRefPubMed
52.
Danilin S, Sourbier C, Thomas L, Lindner V, Rothhut S, Dormoy V, et al. Role of the RNA-binding protein HuR in human renal cell carcinoma. Carcinogenesis. 2010;31:1018–26.CrossRefPubMed
53.
Shang D, Liu Y, Yang P, Chen Y, Tian Y. TGFBI-promoted adhesion, migration and invasion of human renal cell carcinoma depends on inactivation of von Hippel-Lindau tumor suppressor. Urology. 2012;79:966. e961-967.CrossRefPubMed
54.
Juengel E, Dauselt A, Makarevic J, Wiesner C, Tsaur I, Bartsch G, et al. Acetylation of histone H3 prevents resistance development caused by chronic mTOR inhibition in renal cell carcinoma cells. Cancer Lett. 2012;324:83–90.CrossRefPubMed
55.
Ge Q, Xu JJ, Evans DM, Mixson AJ, Yang HY, Lu PY. Leveraging therapeutic potential of multi-targeted siRNA inhibitors. Future Med Chem. 2009;1:1671–81.CrossRefPubMed
56.
Liu K, Chen H, You Q, Shi H, Wang Z. The siRNA cocktail targeting VEGF and HER2 inhibition on the proliferation and induced apoptosis of gastric cancer cell. Mol Cell Biochem. 2014;386:117–24.CrossRefPubMedCentralPubMed
57.
Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol. 2003;21:635–7.CrossRefPubMed
58.
Jackson AL, Burchard J, Schelter J, Chau BN, Cleary M, Lim L, et al. Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity. RNA. 2006;12:1179–87.CrossRefPubMedCentralPubMed
59.
Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov. 2010;9:57–67.CrossRefPubMed
60.
Lin X, Ruan X, Anderson MG, McDowell JA, Kroeger PE, Fesik SW, et al. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res. 2005;33:4527–35.CrossRefPubMedCentralPubMed
61.
Kabilova TO, Meschaninova MI, Venyaminova AG, Nikolin VP, Zenkova MA, Vlassov VV, et al. Short double-stranded RNA with immunostimulatory activity: sequence dependence. Nucleic Acid Ther. 2012;22:196–204.PubMed
62.
63.
Yang C, Li L, Xue Y, Zhao Z, Zhao T, Jia Y, et al. Innate immunity activation involved in unprotected porcine auto-transplant kidneys preserved by naked caspase-3 siRNA. J Transl Med. 2013;11:210.CrossRefPubMedCentralPubMed
64.
65.
Choe J, Kelker MS, Wilson IA. Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science. 2005;309:581–5.CrossRefPubMed
66.
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413:732–8.CrossRefPubMed
67.
Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med. 2005;11:263–70.CrossRefPubMed
68.
Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol. 2005;23:457–62.CrossRefPubMed
69.
Sioud M. Induction of inflammatory cytokines and interferon responses by double-stranded and single-stranded siRNAs is sequence-dependent and requires endosomal localization. J Mol Biol. 2005;348:1079–90.CrossRefPubMed
70.
Racz Z, Godo M, Revesz C, Hamar P. Immune activation and target organ damage are consequences of hydrodynamic treatment but not delivery of naked siRNAs in mice. Nucleic Acid Ther. 2011;21:215–24.CrossRefPubMedCentralPubMed
71.
Mueller TF, Reeve J, Jhangri GS, Mengel M, Jacaj Z, Cairo L, et al. The transcriptome of the implant biopsy identifies donor kidneys at increased risk of delayed graft function. Am J Transplant. 2008;8:78–85.PubMed
72.
Wilflingseder J, Sunzenauer J, Toronyi E, Heinzel A, Kainz A, Mayer B, et al. Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles. PLoS One. 2014;9:e104164.CrossRefPubMedCentralPubMed
73.
Wu D, Zhu D, Xu M, Rong R, Tang Q, Wang X, et al. Analysis of transcriptional factors and regulation networks in patients with acute renal allograft rejection. J Proteome Res. 2011;10:175–81.CrossRefPubMed
74.
Wu D, Liu X, Liu C, Liu Z, Xu M, Rong R, et al. Network analysis reveals roles of inflammatory factors in different phenotypes of kidney transplant patients. J Theor Biol. 2014;362:62–8.CrossRefPubMed
75.
Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006;441:537–41.CrossRefPubMed
76.
Ojima I. Guided molecular missiles for tumor-targeting chemotherapy–case studies using the second-generation taxoids as warheads. Acc Chem Res. 2008;41:108–19.CrossRefPubMed
77.
Mokhtarieh AA, Cheong S, Kim S, Chung BH, Lee MK. Asymmetric liposome particles with highly efficient encapsulation of siRNA and without nonspecific cell penetration suitable for target-specific delivery. Biochim Biophys Acta. 1818;2012:1633–41.
78.
Valencia-Serna J, Gul-Uludag H, Mahdipoor P, Jiang X, Uludag H. Investigating siRNA delivery to chronic myeloid leukemia K562 cells with lipophilic polymers for therapeutic BCR-ABL down-regulation. J Control Release. 2013;172:495–503.CrossRefPubMed
79.
Oe Y, Christie RJ, Naito M, Low SA, Fukushima S, Toh K, et al. Actively-targeted polyion complex micelles stabilized by cholesterol and disulfide cross-linking for systemic delivery of siRNA to solid tumors. Biomaterials. 2014;35:7887–95.CrossRefPubMed
80.
Zhou J, Neff CP, Liu X, Zhang J, Li H, Smith DD, et al. Systemic administration of combinatorial dsiRNAs via nanoparticles efficiently suppresses HIV-1 infection in humanized mice. Mol Ther. 2011;19:2228–38.CrossRefPubMedCentralPubMed
Metadata
Title
Fighting against kidney diseases with small interfering RNA: opportunities and challenges
Authors
Cheng Yang
Chao Zhang
Zitong Zhao
Tongyu Zhu
Bin Yang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2015
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-015-0387-2

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Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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