Strategies and Approaches for siRNA Delivery

  • Dhruvkumar M. Soni Bombay College of Pharmacy, Santacruz (East), Mumbai, India: 400098

Abstract

The present review discusses about RNA interference (RNAi) and its significance in gene therapy. The review mainly focuses on small interference RNA (siRNA) as a mediator of RNAi, its therapeutic benefits and various formulation strategies employed to overcome siRNA delivery hurdles. RNAi is a regulatory process which occurs endogenously within the cell wherein short double-stranded RNA (siRNA) effects sequence-specific posttranscriptional gene silencing. Even though siRNA assists researchers with its powerful therapeutic benefits, there are significant hurdles in developing efficient delivery systems for its systemic administration. These are extracellular and intracellular barriers for siRNA delivery. The present review addresses about pros and cons of gene therapy and superior advantages provided by siRNA over plasmid DNA in gene therapy. It also discloses about the discovery, mechanism of action, significance and applications of siRNA based gene therapies, challenges in its delivery and strategies for overcoming delivery hurdles. Furthermore, emphasis is provided on viral and non – viral vector based siRNA delivery and the significance of lipid based siRNA delivery, the lipoplexes over polymer based siRNA delivery - the polyplexes, followed by recent advances in siRNA based technologies directed against variety of diseases.


Keywords: Endosomal escape, gene therapy, lipoplexes, polyplexes, siRNA, vectors.

Keywords: Endosomal escape, gene therapy, lipoplexes, polyplexes, siRNA, vectors

Downloads

Download data is not yet available.

Author Biography

Dhruvkumar M. Soni, Bombay College of Pharmacy, Santacruz (East), Mumbai, India: 400098

Bombay College of Pharmacy, Santacruz (East), Mumbai, India: 400098

References

1. Zhang XX, McIntosh TJ, Grinstaff MW. Functional lipids and lipoplexes for improved gene delivery. Biochimie. 2012; 94(1):42-58.
2. Pearson S, Jia H, Kandachi K. China approves first gene therapy. Nat Biotechnol. 2004; 22(1):3-4.
3. Wilson JM. Gendicine: the first commercial gene therapy product. Hum Gene Ther. 2005; 16(9):1014-5.
4. Tseng YC, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv Drug Deliv Rev. 2009; 61(9):721-31.
5. Davidson BL, Paulson HL. Molecular medicine for the brain: silencing of disease genes with RNA interference. Lancet Neurol. 2004; 3(3):145-9.
6. Pardridge WM. shRNA and siRNA delivery to the brain. Adv Drug Deliv Rev. 2007; 59(2-3):141-52.
7. Oh YK, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 2009; 61(10):850-62.
8. Patil S, Lalani R, Bhatt P, Vhora I, Patel V, Patel H, et al. Hydroxyethyl substituted linear polyethylenimine for safe and efficient delivery of siRNA therapeutics. RSC Advances. 2018; 8:35461-73.
9. Xie FY, Woodle MC, Lu PY. Harnessing in vivo siRNA delivery for drug discovery and therapeutic development. Drug Discov Today. 2006; 11(1-2):67-73.
10. Das B, Yeger H, Tsuchida R, Torkin R, Gee MF, Thorner PS, et al. A hypoxia-driven vascular endothelial growth factor/Flt1 autocrine loop interacts with hypoxia-inducible factor-1alpha through mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathway in neuroblastoma. Cancer Res. 2005; 65(16):7267-75.
11. Patil S, Bhatt P, Lalani R, Amrutiya J, Vhora I, Kolte A, et al. Low molecular weight chitosan–protamine conjugate for siRNA delivery with enhanced stability and transfection efficiency. RSC Advances. 2016; 6(112):110951-63.
12. Kou R, SenBanerjee S, Jain MK, Michel T. Differential regulation of vascular endothelial growth factor receptors (VEGFR) revealed by RNA interference: interactions of VEGFR-1 and VEGFR-2 in endothelial cell signaling. Biochemistry. 2005; 44(45):15064-73.
13. Takei Y, Kadomatsu K, Yuzawa Y, Matsuo S, Muramatsu T. A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics. Cancer Res. 2004; 64(10):3365-70.
14. Potter H. Electroporation in biology: methods, applications, and instrumentation. Anal Biochem. 1988;174(2):361-73.
15. Mir LM, Bureau MF, Gehl J, Rangara R, Rouy D, Caillaud JM, et al. High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc Natl Acad Sci U S A. 1999; 96(8):4262-7.
16. Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci U S A. 1993; 90(24):11478-82.
17. Wells DJ. Electroporation and ultrasound enhanced non-viral gene delivery in vitro and in vivo. Cell Biol Toxicol. 2010;26(1):21-8.
18. Yoon CS, Park JH. Ultrasound-mediated gene delivery. Expert Opin Drug Deliv. 2010; 7(3):321-30.
19. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, et al. Direct gene transfer into mouse muscle in vivo. Science. 1990; 247(4949 Pt 1):1465-8.
20. Napoli C, Lemieux C, Jorgensen R. Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. Plant Cell. 1990; 2(4):279-89.
21. 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(6669):806-11.
22. McManus MT, Sharp PA. Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 2002;3(10):737-47.
23. 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.
24. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31.
25. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73.
26. McBride JL, Boudreau RL, Harper SQ, Staber PD, Monteys AM, Martins I, et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc Natl Acad Sci U S A. 2008; 105(15):5868-73.
27. Soifer HS, Rossi JJ, Saetrom P. MicroRNAs in disease and potential therapeutic applications. Mol Ther. 2007; 15(12):2070-9.
28. Zhang H, Kolb FA, Jaskiewicz L, Westhof E, Filipowicz W. Single processing center models for human Dicer and bacterial RNase III. Cell. 2004; 118(1):57-68.
29. Meister G, Landthaler M, Patkaniowska A, Dorsett Y, Teng G, Tuschl T. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell. 2004; 15(2):185-97.
30. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009; 10(2):126-39.
31. Monaghan M, Pandit A. RNA interference therapy via functionalized scaffolds. Adv Drug Deliv Rev. 2011; 63(4-5):197-208.
32. Yuan X, Naguib S, Wu Z. Recent advances of siRNA delivery by nanoparticles. Expert Opinion on Drug Delivery. 2011; 8(4):521-36.
33. Miller VM, Gouvion CM, Davidson BL, Paulson HL. Targeting Alzheimer's disease genes with RNA interference: an efficient strategy for silencing mutant alleles. Nucleic Acids Res. 2004; 32(2):661-8.
34. Tros de Ilarduya C, Sun Y, Duzgunes N. Gene delivery by lipoplexes and polyplexes. Eur J Pharm Sci. 2010; 40(3):159-70.
35. Ma B, Zhang S, Jiang H, Zhao B, Lv H. Lipoplex morphologies and their influences on transfection efficiency in gene delivery. J Control Release. 2007; 123(3):184-94.
36. Srinivasan C, Burgess DJ. Optimization and characterization of anionic lipoplexes for gene delivery. J Control Release. 2009; 136(1):62-70.
37. ur Rehman Z, Hoekstra D, Zuhorn IS. Mechanism of polyplex- and lipoplex-mediated delivery of nucleic acids: real-time visualization of transient membrane destabilization without endosomal lysis. ACS Nano. 2013; 7(5):3767-77.
38. Schlegel A, Largeau C, Bigey P, Bessodes M, Lebozec K, Scherman D, et al. Anionic polymers for decreased toxicity and enhanced in vivo delivery of siRNA complexed with cationic liposomes. J Control Release. 2011; 152(3):393-401.
39. Yuan X, Naguib S, Wu Z. Recent advances of siRNA delivery by nanoparticles. Expert Opin Drug Deliv. 2011; 8(4):521-36.
40. Katas H, Cevher E, Alpar HO. Preparation of polyethyleneimine incorporated poly(D,L-lactide-co-glycolide) nanoparticles by spontaneous emulsion diffusion method for small interfering RNA delivery. Int J Pharm. 2009; 369(1-2):144-54.
41. Liu X. [Chitosan-siRNA complex nanoparticles for gene silencing]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010; 27(1):97-101.
42. Yuan X, Li L, Rathinavelu A, Hao J, Narasimhan M, He M, et al. SiRNA drug delivery by biodegradable polymeric nanoparticles. J Nanosci Nanotechnol. 2006; 6(9-10):2821-8.
43. Kim HK, Davaa E, Myung CS, Park JS. Enhanced siRNA delivery using cationic liposomes with new polyarginine-conjugated PEG-lipid. Int J Pharm. 2010; 392(1-2):141-7.
44. Tagami T, Suzuki T, Matsunaga M, Nakamura K, Moriyoshi N, Ishida T, et al. Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery. Int J Pharm. 2012; 422(1-2):280-9.
45. Geusens B, Lambert J, De Smedt SC, Buyens K, Sanders NN, Van Gele M. Ultradeformable cationic liposomes for delivery of small interfering RNA (siRNA) into human primary melanocytes. J Control Release. 2009; 133(3):214-20.
46. Han SE, Kang H, Shim GY, Suh MS, Kim SJ, Kim JS, et al. Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA. Int J Pharm. 2008; 353(1-2):260-9.
Statistics
9 Views | 1 Downloads
How to Cite
1.
Soni DM. Strategies and Approaches for siRNA Delivery. JDDT [Internet]. 15Jun.2020 [cited 6Jul.2020];10(3-s):239-50. Available from: http://jddtonline.info/index.php/jddt/article/view/4086