Research progress of microRNA and its non-viral vector in intervertebral disc degeneration_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

HUANG Yong ,  FENG Ganjun , LIU Limin , LI Tao , LIU Hao ,  SONG Yueming

Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;

Corresponding author：

FENG Ganjun, Email: gjfenghx@163.com; SONG Yueming, Email: hx_sym@163.com

Keywords：

Intervertebral disc degeneration; microRNA; non-viral vector; gene therapy

DOI：

10.7507/1002-1892.201609092

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the research progress of microRNA (miRNA) and its non-viral vector in intervertebral disc degeneration (IDD) and to investigate the potential of non-viral vector delivery of miRNA in clinical application. Methods The related literature about the role of miRNA in IDD and its non-viral delivery system was reviewed and analyzed. Results MiRNA can regulate the related gene expression level and further participate in the pathophysiologic process in degenerated intervertebral disc, miRNA delivered by various non-viral vectors has obtained an ideal effect in some diseases. Conclusion MiRNA plays a great role in the cellular and molecular mechanisms of IDD, as a safe and effective strategy for gene therapy, non-viral vector provides new possibilities for IDD treated with miRNA.

Citation： HUANGYong, FENGGanjun, LIULimin, LITao, LIUHao, SONGYueming. Research progress of microRNA and its non-viral vector in intervertebral disc degeneration. Chinese Journal of Reparative and Reconstructive Surgery, 2017, 31(1): 116-121. doi: 10.7507/1002-1892.201609092 Copy

1.	Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012, 380(9859): 2163-2196.
2.	Pereira DR, Silva-Correia J, Oliveira JM, et al. Hydrogels in acellular and cellular strategies for intervertebral disc regeneration. J Tissue Eng Regen Med, 2013, 7(2): 85-98.
3.	Zhang YG, Sun Z, Zhang Z, et al. Risk factors for lumbar intervertebral disc herniation in Chinese population: a case-control study. Spine (Phila Pa 1976), 2009, 34(25): E918-922.
4.	Chou J, Shahi P, Werb Z. microRNA-mediated regulation of the tumor microenvironment. Cell Cycle, 2013, 12(20): 3262-3271.
5.	Farazi TA, Spitzer JI, Morozov P, et al. miRNAs in human cancer. J Pathol, 2011, 223(2): 102-115.
6.	Economou EK, Oikonomou E, Siasos G, et al. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis, 2015, 241(2): 624-633.
7.	Wang C, Wang WJ, Yan YG, et al. MicroRNAs: New players in intervertebral disc degeneration. Clin Chim Acta, 2015, 450: 333-341.
8.	Christopher AF, Kaur RP, Kaur G, et al. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res, 2016, 7(2): 68-74.
9.	Zacchigna S, Zentilin L, Giacca M. Adeno-associated virus vectors as therapeutic and investigational tools in the cardiovascular system. Circ Res, 2014, 114(11): 1827-1846.
10.	Eulalio A, Mano M, Dal Ferro M, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature, 2012, 492(7429): 376-381.
11.	Zhao B, Yu Q, Li H, et al. Characterization of microRNA expression profiles in patients with intervertebral disc degeneration. Int J Mol Med, 2014, 33(1): 43-50.
12.	Liu X, Che L, Xie YK, et al. Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study. Genom Data, 2015, 5: 80-81.
13.	Li HR, Cui Q, Dong ZY, et al. Downregulation of miR-27b is Involved in Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 13(MMP13) in Human Intervertebral Disc Degeneration. Spine (Phila Pa 1976), 2016, 41(3): E116-123.
14.	Ji ML, Zhang XJ, Shi PL, et al. Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14. J Mol Med (Berl), 2016, 94(4): 457-468.
15.	Xu YQ, Zhang ZH, Zheng YF, et al. Dysregulated miR-133a Mediates Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 9(MMP9) in Human Intervertebral Disc Degeneration. Spine (Phila Pa 1976), 2016, 41(12): E717-724.
16.	Ji ML, Lu J, Shi PL, et al. Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration. J Bone Miner Res, 2016, 31(4): 900-909.
17.	Wang HQ, Yu XD, Liu ZH, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol, 2011, 225(2): 232-242.
18.	Hu P, Feng B, Wang G, et al. Microarray based analysis of gene regulation by microRNA in intervertebral disc degeneration. Mol Med Rep, 2015, 12(4): 4925-4930.
19.	孔敬波, 马信龙, 王涛, 等. Wnt/β-catenin 及 NF-кB 信号通路与椎间盘退变的研究进展. 中国修复重建外科杂志, 2013, 27(12): 1523-1528.
20.	Ohrt-Nissen S, Dossing KB, Rossing M, et al. Characterization of miRNA expression in human degenerative lumbar disks. Connect Tissue Res, 2013, 54(3): 197-203.
21.	Liu H, Huang X, Liu X, et al. miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci, 2014, 15(3): 4007-4018.
22.	Yu X, Li Z, Shen J, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One, 2013, 8(12): e83080.
23.	Li W, Wang P, Zhang Z, et al. MiR-184 regulates proliferation in nucleus pulposus cells by targeting GAS1. World Neurosurg, 2016. [Epub ahead of print].
24.	Chen B, Huang SG, Ju L, et al. Effect of microRNA-21 on the proliferation of human degenerated nucleus pulposus by targeting programmed cell death 4. Braz J Med Biol Res, 2016, 49(6): pii: S0100-879X2016000600602. doi: 10.1590/1414-431X20155020.
25.	Yan N, Yu S, Zhang H, et al. Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression. Cell Physiol Biochem, 2015, 36(6): 2229-2236.
26.	Liu ZQ, Fu WQ, Zhao S, et al. Regulation of insulin-like growth factor 1 receptor signaling by microRNA-4458 in the development of lumbar disc degeneration. Am J Transl Res, 2016, 8(5): 2309-2316.
27.	Molinos M, Almeida CR, Caldeira J, et al. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface, 2015, 12(104): 20141191.
28.	Peng Y, Lv FJ. Symptomatic versus Asymptomatic Intervertebral Disc Degeneration: Is Inflammation the Key? Crit Rev Eukaryot Gene Expr, 2015, 25(1): 13-21.
29.	Wang XH, Hong X, Zhu L, et al. Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-kappaB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Exp Biol Med (Maywood), 2015, 240(4): 411-417.
30.	Wang T, Li P, Ma X, et al. MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-alpha-induced apoptosis by targeting JunD. Biochimie, 2015, 115: 1-7.
31.	Liu G, Cao P, Chen H, et al. MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K. PLoS One, 2013, 8(9): e75251.
32.	Liu W, Zhang Y, Feng X, et al. Inhibition of microRNA-34a prevents IL-1beta-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression. Exp Biol Med (Maywood), 2016, 241(17): 1924-1932.
33.	Liu W, Zhang Y, Xia P, et al. MicroRNA-7 regulates IL-1beta-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. Biomed Pharmacother, 2016, 83: 1414-1421.
34.	Chen H, Wang J, Hu B, et al. MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2. Mol Cell Biochem, 2015, 406(1-2): 21-30.
35.	Liu MH, Sun C, Yao Y, et al. Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. Sci Rep, 2016, 6: 25401.
36.	Thurner EM, Krenn-Pilko S, Langsenlehner U, et al. Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy. Strahlenther Onkol, 2014, 190(3): 304-309.
37.	Han W, Zhou Y, Zhong R, et al. Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population. PLoS One, 2013, 8(8): e71656.
38.	Ye D, Dai L, Yao Y, et al. miR-155 Inhibits Nucleus Pulposus Cells^， Degeneration through Targeting ERK 1/2. Dis Markers, 2016, 2016: 6984270.
39.	Zhang DY, Wang ZJ, Yu YB, et al. Role of microRNA-210 in human intervertebral disc degeneration. Exp Ther Med, 2016, 11(6): 2349-2354.
40.	Ma JF, Zang LN, Xi YM, et al. MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration. Cell Physiol Biochem, 2016, 38(1): 295-305.
41.	Jing W, Jiang W. MicroRNA-93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells. Cell Prolif, 2015, 48(3): 284-292.
42.	Gu SX, Li X, Hamilton JL, et al. MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc. Gene, 2015, 555(2): 80-87.
43.	Tsirimonaki E, Fedonidis C, Pneumaticos SG, et al. PKCepsilon signalling activates ERK1/2, and regulates aggrecan, ADAMTS5, and miR377 gene expression in human nucleus pulposus cells. PLoS One, 2013, 8(11): e82045.
44.	Song YQ, Karasugi T, Cheung KM, et al. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Invest, 2013, 123(11): 4909-4917.
45.	Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 2010, 327(5962): 198-201.
46.	Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med, 2013, 368(18): 1685-1694.
47.	Lv H, Zhang S, Wang B, et al. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release, 2006, 114(1): 100-109.
48.	Chen Y, Zhu X, Zhang X, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther, 2010, 18(9): 1650-1656.
49.	Dong X, Lin L, Chen J, et al. Multi-armed poly (aspartate-g-OEI) copolymers as versatile carriers of pDNA/siRNA. Acta Biomater, 2013, 9(6): 6943-6952.
50.	Namgung R, Kim J, Singha K, et al. Synergistic effect of low cytotoxic linear polyethylenimine and multiarm polyethylene glycol: study of physicochemical properties andin vitro gene transfection. Mol Pharm, 2009, 6(6): 1826-1835.
51.	Park IK, Singha K, Arote RB, et al. pH-Responsive Polymers as Gene Carriers. Macromol Rapid Commun, 2010, 31(13): 1122-1133.
52.	Kumar P, Wu H, McBride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature, 2007, 448(7149): 39-43.
53.	Hwang DW, Son S, Jang J, et al. A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials, 2011, 32(21): 4968-4975.
54.	Zhou Y, Zhang L, Zhao W, et al. Nanoparticle-mediated delivery of TGF-beta1 miRNA plasmid for preventing flexor tendon adhesion formation. Biomaterials, 2013, 34(33): 8269-8278.
55.	Kim HY, Kim HN, Lee SJ, et al. Effect of pore sizes of PLGA scaffolds on mechanical properties and cell behaviour for nucleus pulposus regenerationin vivo. J Tissue Eng Regen Med, 2014.[Epub ahead of print].
56.	Devulapally R, Sekar NM, Sekar TV, et al. Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy. ACS Nano, 2015, 9(3): 2290-2302.
57.	Arora S, Swaminathan SK, Kirtane A, et al. Synthesis, characterization, and evaluation of poly (D, L-lactide-co-glycolide)-based nanoformulation of miRNA-150: potential implications for pancreatic cancer therapy. Int J Nanomedicine, 2014, 9: 2933-2942.
58.	Ren Y, Zhou X, Mei M, et al. MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer, 2010, 10: 27.
59.	Sun Z, Song X, Li X,et al. In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model. Nanoscale, 2014, 6(23): 14343-14353.
60.	Crew E, Tessel MA, Rahman S, et al. MicroRNA conjugated gold nanoparticles and cell transfection. Anal Chem, 2012, 84(1): 26-29.
61.	Bitar A, Ahmad NM, Fessi H, et al. Silica-based nanoparticles for biomedical applications. Drug Discov Today, 2012, 17(19-20): 1147-1154.
62.	Masotti A, Miller MR, Celluzzi A, et al. Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyamine-coated carbon nanotubes. Nanomedicine, 2016, 12(6): 1511-1522.

1. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet, 2012, 380(9859): 2163-2196.
2. Pereira DR, Silva-Correia J, Oliveira JM, et al. Hydrogels in acellular and cellular strategies for intervertebral disc regeneration. J Tissue Eng Regen Med, 2013, 7(2): 85-98.
3. Zhang YG, Sun Z, Zhang Z, et al. Risk factors for lumbar intervertebral disc herniation in Chinese population: a case-control study. Spine (Phila Pa 1976), 2009, 34(25): E918-922.
4. Chou J, Shahi P, Werb Z. microRNA-mediated regulation of the tumor microenvironment. Cell Cycle, 2013, 12(20): 3262-3271.
5. Farazi TA, Spitzer JI, Morozov P, et al. miRNAs in human cancer. J Pathol, 2011, 223(2): 102-115.
6. Economou EK, Oikonomou E, Siasos G, et al. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis, 2015, 241(2): 624-633.
7. Wang C, Wang WJ, Yan YG, et al. MicroRNAs: New players in intervertebral disc degeneration. Clin Chim Acta, 2015, 450: 333-341.
8. Christopher AF, Kaur RP, Kaur G, et al. MicroRNA therapeutics: Discovering novel targets and developing specific therapy. Perspect Clin Res, 2016, 7(2): 68-74.
9. Zacchigna S, Zentilin L, Giacca M. Adeno-associated virus vectors as therapeutic and investigational tools in the cardiovascular system. Circ Res, 2014, 114(11): 1827-1846.
10. Eulalio A, Mano M, Dal Ferro M, et al. Functional screening identifies miRNAs inducing cardiac regeneration. Nature, 2012, 492(7429): 376-381.
11. Zhao B, Yu Q, Li H, et al. Characterization of microRNA expression profiles in patients with intervertebral disc degeneration. Int J Mol Med, 2014, 33(1): 43-50.
12. Liu X, Che L, Xie YK, et al. Noncoding RNAs in human intervertebral disc degeneration: An integrated microarray study. Genom Data, 2015, 5: 80-81.
13. Li HR, Cui Q, Dong ZY, et al. Downregulation of miR-27b is Involved in Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 13(MMP13) in Human Intervertebral Disc Degeneration. Spine (Phila Pa 1976), 2016, 41(3): E116-123.
14. Ji ML, Zhang XJ, Shi PL, et al. Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14. J Mol Med (Berl), 2016, 94(4): 457-468.
15. Xu YQ, Zhang ZH, Zheng YF, et al. Dysregulated miR-133a Mediates Loss of Type II Collagen by Directly Targeting Matrix Metalloproteinase 9(MMP9) in Human Intervertebral Disc Degeneration. Spine (Phila Pa 1976), 2016, 41(12): E717-724.
16. Ji ML, Lu J, Shi PL, et al. Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration. J Bone Miner Res, 2016, 31(4): 900-909.
17. Wang HQ, Yu XD, Liu ZH, et al. Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol, 2011, 225(2): 232-242.
18. Hu P, Feng B, Wang G, et al. Microarray based analysis of gene regulation by microRNA in intervertebral disc degeneration. Mol Med Rep, 2015, 12(4): 4925-4930.
19. 孔敬波, 马信龙, 王涛, 等. Wnt/β-catenin 及 NF-кB 信号通路与椎间盘退变的研究进展. 中国修复重建外科杂志, 2013, 27(12): 1523-1528.
20. Ohrt-Nissen S, Dossing KB, Rossing M, et al. Characterization of miRNA expression in human degenerative lumbar disks. Connect Tissue Res, 2013, 54(3): 197-203.
21. Liu H, Huang X, Liu X, et al. miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci, 2014, 15(3): 4007-4018.
22. Yu X, Li Z, Shen J, et al. MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One, 2013, 8(12): e83080.
23. Li W, Wang P, Zhang Z, et al. MiR-184 regulates proliferation in nucleus pulposus cells by targeting GAS1. World Neurosurg, 2016. [Epub ahead of print].
24. Chen B, Huang SG, Ju L, et al. Effect of microRNA-21 on the proliferation of human degenerated nucleus pulposus by targeting programmed cell death 4. Braz J Med Biol Res, 2016, 49(6): pii: S0100-879X2016000600602. doi: 10.1590/1414-431X20155020.
25. Yan N, Yu S, Zhang H, et al. Lumbar Disc Degeneration is Facilitated by MiR-100-Mediated FGFR3 Suppression. Cell Physiol Biochem, 2015, 36(6): 2229-2236.
26. Liu ZQ, Fu WQ, Zhao S, et al. Regulation of insulin-like growth factor 1 receptor signaling by microRNA-4458 in the development of lumbar disc degeneration. Am J Transl Res, 2016, 8(5): 2309-2316.
27. Molinos M, Almeida CR, Caldeira J, et al. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface, 2015, 12(104): 20141191.
28. Peng Y, Lv FJ. Symptomatic versus Asymptomatic Intervertebral Disc Degeneration: Is Inflammation the Key? Crit Rev Eukaryot Gene Expr, 2015, 25(1): 13-21.
29. Wang XH, Hong X, Zhu L, et al. Tumor necrosis factor alpha promotes the proliferation of human nucleus pulposus cells via nuclear factor-kappaB, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Exp Biol Med (Maywood), 2015, 240(4): 411-417.
30. Wang T, Li P, Ma X, et al. MicroRNA-494 inhibition protects nucleus pulposus cells from TNF-alpha-induced apoptosis by targeting JunD. Biochimie, 2015, 115: 1-7.
31. Liu G, Cao P, Chen H, et al. MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K. PLoS One, 2013, 8(9): e75251.
32. Liu W, Zhang Y, Feng X, et al. Inhibition of microRNA-34a prevents IL-1beta-induced extracellular matrix degradation in nucleus pulposus by increasing GDF5 expression. Exp Biol Med (Maywood), 2016, 241(17): 1924-1932.
33. Liu W, Zhang Y, Xia P, et al. MicroRNA-7 regulates IL-1beta-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. Biomed Pharmacother, 2016, 83: 1414-1421.
34. Chen H, Wang J, Hu B, et al. MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2. Mol Cell Biochem, 2015, 406(1-2): 21-30.
35. Liu MH, Sun C, Yao Y, et al. Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression. Sci Rep, 2016, 6: 25401.
36. Thurner EM, Krenn-Pilko S, Langsenlehner U, et al. Association of genetic variants in apoptosis genes FAS and FASL with radiation-induced late toxicity after prostate cancer radiotherapy. Strahlenther Onkol, 2014, 190(3): 304-309.
37. Han W, Zhou Y, Zhong R, et al. Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in Chinese population. PLoS One, 2013, 8(8): e71656.
38. Ye D, Dai L, Yao Y, et al. miR-155 Inhibits Nucleus Pulposus Cells^， Degeneration through Targeting ERK 1/2. Dis Markers, 2016, 2016: 6984270.
39. Zhang DY, Wang ZJ, Yu YB, et al. Role of microRNA-210 in human intervertebral disc degeneration. Exp Ther Med, 2016, 11(6): 2349-2354.
40. Ma JF, Zang LN, Xi YM, et al. MiR-125a Rs12976445 Polymorphism is Associated with the Apoptosis Status of Nucleus Pulposus Cells and the Risk of Intervertebral Disc Degeneration. Cell Physiol Biochem, 2016, 38(1): 295-305.
41. Jing W, Jiang W. MicroRNA-93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells. Cell Prolif, 2015, 48(3): 284-292.
42. Gu SX, Li X, Hamilton JL, et al. MicroRNA-146a reduces IL-1 dependent inflammatory responses in the intervertebral disc. Gene, 2015, 555(2): 80-87.
43. Tsirimonaki E, Fedonidis C, Pneumaticos SG, et al. PKCepsilon signalling activates ERK1/2, and regulates aggrecan, ADAMTS5, and miR377 gene expression in human nucleus pulposus cells. PLoS One, 2013, 8(11): e82045.
44. Song YQ, Karasugi T, Cheung KM, et al. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J Clin Invest, 2013, 123(11): 4909-4917.
45. Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science, 2010, 327(5962): 198-201.
46. Janssen HL, Reesink HW, Lawitz EJ, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med, 2013, 368(18): 1685-1694.
47. Lv H, Zhang S, Wang B, et al. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release, 2006, 114(1): 100-109.
48. Chen Y, Zhu X, Zhang X, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther, 2010, 18(9): 1650-1656.
49. Dong X, Lin L, Chen J, et al. Multi-armed poly (aspartate-g-OEI) copolymers as versatile carriers of pDNA/siRNA. Acta Biomater, 2013, 9(6): 6943-6952.
50. Namgung R, Kim J, Singha K, et al. Synergistic effect of low cytotoxic linear polyethylenimine and multiarm polyethylene glycol: study of physicochemical properties andin vitro gene transfection. Mol Pharm, 2009, 6(6): 1826-1835.
51. Park IK, Singha K, Arote RB, et al. pH-Responsive Polymers as Gene Carriers. Macromol Rapid Commun, 2010, 31(13): 1122-1133.
52. Kumar P, Wu H, McBride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature, 2007, 448(7149): 39-43.
53. Hwang DW, Son S, Jang J, et al. A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA. Biomaterials, 2011, 32(21): 4968-4975.
54. Zhou Y, Zhang L, Zhao W, et al. Nanoparticle-mediated delivery of TGF-beta1 miRNA plasmid for preventing flexor tendon adhesion formation. Biomaterials, 2013, 34(33): 8269-8278.
55. Kim HY, Kim HN, Lee SJ, et al. Effect of pore sizes of PLGA scaffolds on mechanical properties and cell behaviour for nucleus pulposus regenerationin vivo. J Tissue Eng Regen Med, 2014.[Epub ahead of print].
56. Devulapally R, Sekar NM, Sekar TV, et al. Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy. ACS Nano, 2015, 9(3): 2290-2302.
57. Arora S, Swaminathan SK, Kirtane A, et al. Synthesis, characterization, and evaluation of poly (D, L-lactide-co-glycolide)-based nanoformulation of miRNA-150: potential implications for pancreatic cancer therapy. Int J Nanomedicine, 2014, 9: 2933-2942.
58. Ren Y, Zhou X, Mei M, et al. MicroRNA-21 inhibitor sensitizes human glioblastoma cells U251 (PTEN-mutant) and LN229 (PTEN-wild type) to taxol. BMC Cancer, 2010, 10: 27.
59. Sun Z, Song X, Li X,et al. In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model. Nanoscale, 2014, 6(23): 14343-14353.
60. Crew E, Tessel MA, Rahman S, et al. MicroRNA conjugated gold nanoparticles and cell transfection. Anal Chem, 2012, 84(1): 26-29.
61. Bitar A, Ahmad NM, Fessi H, et al. Silica-based nanoparticles for biomedical applications. Drug Discov Today, 2012, 17(19-20): 1147-1154.
62. Masotti A, Miller MR, Celluzzi A, et al. Regulation of angiogenesis through the efficient delivery of microRNAs into endothelial cells using polyamine-coated carbon nanotubes. Nanomedicine, 2016, 12(6): 1511-1522.

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