Limitations of Clinical Application of siRNA Delivery Based on Non-Viral Vectors

Document Type : Review Article

Authors

1 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

In recent years, much more attentions have been focused on siRNA-based gene therapy. This approach is based on PTGS (Post-transcriptional gene silencing). Due to some defects in viral vectors, non-viral vectors have been used to deliver nucleic acids into target cells. Although, transfection efficiency in non-viral vectors is less than viral ones, but safety of non-viral vectors is much more. Characteristic features of siRNA, such as high compatibility, application in low doses and its versatility make it suitable in the gene therapy field. However, some challenges, such as stimulating immune system and Off-target silencing will be remain. In this review article, we express bottlenecks existing in siRNA delivery into target cells. According to the information, with further development of siRNA delivery in the future, it could be a promising approach in treatment for a variety of genetic diseases.

Keywords

References

  1. Hoag H. Careers and Recruitment Gene therapy rising? Nature 2005; 435: 530-1.
  2. Hollon T. Researchers and regulators reflect on first gene therapy death. Am J Ophthalmol 2000; 129(5): 701.
  3. Xu J, Ganesh S, Amiji M. Non-condensing polymeric nanoparticles for targeted gene and siRNA delivery. Int J Pharm 2012; 427(1): 21-34.
  4. Hannon GJ. RNA interference. Nature 2002; 418(6894): 244-51.
  5. 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(6836): 494-8.
  6. Guo P, Coban O, Snead NM, Trebley J, Hoeprich S, Guo S, et al. Engineering RNA for targeted siRNA delivery and medical application. Adv Drug Deliv Rev 2010; 62(6): 650-66.
  7. 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(1-2): 64-73.
  8. Buyens K, De Smedt SC, Braeckmans K, Demeester J, Peeters L, van Grunsven LA, et al. Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design. J Control Release 2012; 158(3): 362-70.
  9. Aagaard L, Rossi JJ. RNAi therapeutics: principles, prospects and challenges. Adv Drug Deliv Rev 2007; 59(2-3): 75-86.
  10. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003; 115(2): 199-208.
  11. David S, Pitard B, Benoit JP, Passirani C. Non-viral nanosystems for systemic siRNA delivery. Pharmacol Res 2010; 62(2): 100-14.
  12. Xu S, Dong M, Liu X, Howard KA, Kjems J, Besenbacher F. Direct force measurements between siRNA and chitosan molecules using force spectroscopy. Biophys J 2007; 93(3): 952-9.
  13. Gao H, Shi W, Freund LB. Mechanics of receptor-mediated endocytosis. Proceedings of the National Academy of Sciences of the United States of America 2005; 102(27): 9469-74.
  14. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. J Control Release 2006; 116(2): 123-9.
  15. Bartlett DW, Davis ME. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res 2006; 34(1): 322-33.
  16. Braasch DA, Paroo Z, Constantinescu A, Ren G, Oz OK, Mason RP, et al. Biodistribution of phosphodiester and phosphorothioate siRNA. Bioorg Med Chem Lett 2004; 14(5): 1139-43.
  17. Chiu YL, Rana TM. siRNA function in RNAi: a chemical modification analysis. RNA 2003; 9(9): 1034-48.
  18. Soutschek J, Akinc A, Bramlage B, Charisse K, Constien R, Donoghue M, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004; 432(7014): 173-8.
  19. Tong AW, Jay CM, Senzer N, Maples PB, Nemunaitis J. Systemic therapeutic gene delivery for cancer: crafting Paris' arrow. Curr Gene Ther 2009; 9(1): 45-60.
  20. Zelphati O, Uyechi LS, Barron LG, Szoka FC, Jr. Effect of serum components on the physico-chemical properties of cationic lipid/oligonucleotide complexes and on their interactions with cells. Biochim Biophys Acta 1998; 1390(2): 119-33.
  21. Ogris M, Wagner E. Targeting tumors with non-viral gene delivery systems. Drug Discov Today 2002; 7(8): 479-85.
  22. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 2001; 41: 189-207.
  23. Sato A, Takagi M, Shimamoto A, Kawakami S, Hashida M. Small interfering RNA delivery to the liver by intravenous administration of galactosylated cationic liposomes in mice. Biomaterials 2007; 28(7): 1434-42.
  24. Pichler A, Zelcer N, Prior JL, Kuil AJ, Piwnica-Worms D. In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein. Clin Cancer Res 2005; 11(12): 4487-94.
  25. Yonesaka K, Tamura K, Kurata T, Satoh T, Ikeda M, Fukuoka M, et al. Small interfering RNA targeting survivin sensitizes lung cancer cell with mutant p53 to adriamycin. Int J Cancer 2006; 118(4): 812-20.
  26. Ning S, Fuessel S, Kotzsch M, Kraemer K, Kappler M, Schmidt U, et al. siRNA-mediated down-regulation of survivin inhibits bladder cancer cell growth. Int J Oncol 2004; 25(4): 1065-71.
  27. 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(3): 263-70.
  28. Marques JT, Williams BR. Activation of the mammalian immune system by siRNAs. Nat Biotechnol 2005; 23(11): 1399-405.
  29. 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(6): 635-7.
  30. 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(14): 4527-35.
  31. Jackson AL, Burchard J, Leake D, Reynolds A, Schelter J, Guo J, et al. Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing. RNA 2006; 12(7): 1197-205.
  32. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 1995; 92(16): 7297-301.
  33. Zelphati O, Szoka FC, Jr. Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci U S A 1996; 93(21):
  34. -8.
  35. Abrams MT, Koser ML, Seitzer J, Williams SC, DiPietro MA, Wang W, et al. Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol Ther 2010; 18(1): 171-80.
  36. Li SD, Huang L. Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J Control Release 2010; 145(3): 178-81.
  37. Laverman P, Carstens MG, Boerman OC, Dams ET, Oyen WJ, van RN, et al. Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection. J Pharmacol Exp Ther 2001; 298(2): 607-12.
  38. Koide H, Asai T, Hatanaka K, Urakami T, Ishii T, Kenjo E, et al. Particle size-dependent triggering of accelerated blood clearance phenomenon. Int J Pharm 2008; 362(1-2): 197-200.
  39. Howard KA. Delivery of RNA interference therapeutics using polycation-based nanoparticles. Adv Drug Deliv Rev 2009; 61(9): 710-20.
  40. Wu SY, McMillan NA. Lipidic systems for in vivo siRNA delivery. AAPS J 2009; 11(4): 639-52.
  41. Li W, Szoka FC, Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm Res 2007; 24(3): 438-49.
  42. Lam JK, Liang W, Chan HK. Pulmonary delivery of therapeutic siRNA. Adv Drug Deliv Rev 2012; 64(1): 1-15.
  43. Ramachandran PV, Ignacimuthu S. RNA interference--a silent but an efficient therapeutic tool. Appl Biochem Biotechnol 2013; 169(6): 1774-89.
  44. McNamara JO, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, et al. Cell type–specific delivery of siRNAs with aptamer-siRNA chimeras. Nature Biotechnology 2006; 24: 1005-15.
  45. Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res 2005; 65: 8984.
  46. Cui Y, Wang Q, Wang J, Dong Y, Luo C, Hu G, et al. Knockdown of AKT2 expression by RNA interference inhibits proliferation, enhances apoptosis, and increases chemosensitivity to the anticancer drug VM-26 in U87 glioma cells. Brain Res 2012; 1469: 1-9.
  47. Zhang Z, Wang J, Shen B, Peng C, Zheng M. The ABCC4 gene is a promising target for pancreatic cancer therapy. Gene 2012; 491(2): 194-9.
  48. Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J. Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci U S A 2004; 101(23): 8676-81.
  49. Fechner H, Sipo I, Westermann D, Pinkert S, Wang X, Suckau L, et al. Cardiac-targeted RNA interference mediated by an AAV9 vector improves cardiac function in coxsackievirus B3 cardiomyopathy. J Mol Med (Berl) 2008; 86(9): 987-97.
  50. DeVincenzo J, Lambkin-Williams R, Wilkinson T, Cehelsky J, Nochur S, Walsh E, et al. A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus. Proc Natl Acad Sci U S A 2010; 107(19): 8800-5.
  51. McCaffrey AP, Nakai H, Pandey K, Huang Z, Salazar FH, Xu H, et al. Inhibition of hepatitis B virus in mice by RNA interference. Nat Biotechnol 2003; 21(6): 639-44.
  52. Martinez MA, Clotet B, Este JA. RNA interference of HIV replication. Trends Immunol 2002; 23(12): 559-61.
  53. Ng EW, Adamis AP. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can J Ophthalmol 2005; 40(3): 352-68.
  54. Zwicky R, Muntener K, Goldring MB, Baici A. Cathepsin B expression and down-regulation by gene silencing and antisense DNA in human chondrocytes. Biochem J 2002; 367(Pt 1): 209-17.
Journal of Isfahan Medical School
Volume 32, Issue 272 - Serial Number 272
January and February 2014
Pages 34-49

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History

  • Receive Date: 29 September 2013
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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