Translational siRNA Therapeutics using liposomal carriers: Prospects & challenges

Current Gene Therapy

Volumn 12, Issue 4, 2012, Pages 315-332

  Bhavsar, Dhiraj ^a   Subramanian, Krishnakumar ^b   Sethuraman, Swaminathan ^a   Krishnan, Uma Maheswari ^a  

^a SASTRA UNIVERSITY   (India)

^b VISION RESEARCH FOUNDATION   (India)

Author keywords

Cationic liposomes; Designer lipids; Hybrid liposomes; SiRNA

Indexed keywords

LIPOSOME; SHORT HAIRPIN RNA; SMALL INTERFERING RNA;

DRUG TARGETING; GENE DELIVERY SYSTEM; GENE THERAPY; HUMAN; NONHUMAN; REVIEW; RNA INTERFERENCE; RNA TRANSLATION;

CATIONS; CHITOSAN; GENE SILENCING; GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; LIPIDS; LIPOSOMES; RNA, SMALL INTERFERING;

EID: 84864532803     PISSN: 15665232     EISSN: 18755631     Source Type: Journal    
DOI: 10.2174/156652312802083611     Document Type: Review

References (171)

1. Olivier V. RNA silencing as a plant immunesystem against viruses. Trends Genet 2001; 17: 449-59.
2. Elbashir SM, Harborthj, Lendeckel W, Yalcin A, Weber K & Tuschl T. Duplexes of 21 ± nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001; 14: 494-8.
3. Fire A, Xu S, Montgomery MK. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391: 806-11.
4. Elbashir MS, Winfried L, Tuschi T. RNA interference is mediated by 21-and 22-nucleotide RNAs Genes Dev 2001; 15: 188-200.
5. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs Exhibit Strand Bias. Cell 2003; 115: 209-16.
6. Martinez J, Patkaniowska A, Urlaub H. Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi. Cell 2002; 110: 563-74.
7. Zamore PD, Tuschl T, Sharp PA, Bartel DP. RNAi: Doublestranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide Intervals. Cell 2000; 101: 25-33.
8. Bryan R Cullen. Enhancing and confirming the specificity of RNAi experiments. Nat Methods 2006; 3: 677-681.
9. Schambach A, Baum C. Clinical application of lentiviral vectors-concepts and practice. Curr Gene Ther 2008; 8: 474-82.
10. Pauwels K, Gijsbers R, Toelen J, Schambach A, Willard-Gallo K, Verheust C, et. al. State-of-the-Art Lentiviral Vectors for Research Use: Risk assessment and biosafety recommendations. Curr Gene Ther 2009; 9: 459-74.
11. Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, et. al. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther 2012; 20: 679-86.
12. Li MJ, Kim J, Li S, Zaia J, Yee JK, Anderson J, et. al. Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther. 2005; 12: 900-9.
13. Rao DD, Vorhies JS, Senzer N, Nemunaitis J. siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev 2009; 25: 746-59.
14. Jang JY, Jeon YK, Kim CW. Degradation of HER2/neu by ANT2 shRNA suppresses migration and invasiveness of breast cancer cells. BMC Cancer 2010; 10: 391.
15. Ryou SM, Kim S, Jang HH, Kim JH, Yeom JH, Eom MS. et al. Delivery of shRNA using gold nanoparticle-DNA oligonucleotide conjugates as a universal carrier. Biochem Biophys Res Commun 2010; 398: 542-6.
16. Saxena S, Jónsson Z, and Dutta A. Small RNAs with imperfect match to endogenous mRNA Repress Translation. J Bio Chem 2003; 278: 44312-19.
17. Holen T, Amarzguioui M, Wiiger MT, Babaie E, prdyz H. Potential effects of small interfering RNAs targeting the human coagulation trigger growth factor. Nucleic Acids Res 2002; 30: 1757-66.
18. Elbashir SM, Martinez J, Patkaniowska A, Lendeckel W. Tuschl T. Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. EMBO J 2001; 20: 6877-88.
19. Elbashir SM, Harborth J, Weber K, Tuschl T. Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 2002; 26: 199-213.
20. Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A. Rational siRNA design for RNA interference. Nat Biotechnol 2004; 22: 326-30.
21. Kim DH, Behlke MA, Rose SD, Chang MS, Choi S, Rossi JJ. Synthetic dsRNA dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol 2005; 23: 222-6.
22. Wang L, Mu FY. Web-based design center for vector-based siRNA and siRNA cassette. Bioinformatics 2004; 20: 1818-20.
23. Pei Y, Tuschl T. On the art of identifying effective and specific siRNAs. Nat Methods 2006; 3: 670-6
24. Yiu SM, Wong PW, Lam TW et al. Filtering of Ineffective siRNAs and Improved siRNA Design Tool. Bioinformatics 2005; 21: 144-51.
25. Birmingham A, Anderson EM, Reynolds A, et al. 3' UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat Methods 2006; 3: 199-204.
26. Jackson AL, Burchard J, Schelter, et al. Widespread siRNA"offtarget" transcript silencing by seed region sequence complementarity. RNA 2006; 12: 1179-87.
27. Ehasani A, Saetrom p, Zhang J, et al. Rational design of micro-RNA-like bifunctional siRNA targeting HIV and the HIV coreceptor CCR5. Mol Ther 2010; 18: 796-802.
28. Morrissey DV, Lockridge JA, Shaw L, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 2005; 23: 1002-7.
29. Dykxhoorn DK, Lieberman J, Knocking down Disease with siRNAs. Cell 2006; 126: 231-5.
30. de Fougerolles A, Vornloche HP, Maraganore J, Lieberman J. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 2007; 6: 443-53.
31. Schiffelers RM, Xu J, Storm G, Woodle MC, Scaria. Effects of treatment with small interfering RNA on joint inflammation in mice with collagen-induced arthritis. Arthritis Rheum 2005; 52: 1314-18.
32. Chen Y, Stamatoyannopoulos G, Song CZ. Down-regulation of CXCR4 by inducible small interfering in vitro RNA inhibits breast cancer cell invasion. Cancer Res 2003; 63: 4801-04.
33. Zhang P, Singh A. Yegnasubramanian S. Loss of Keap1 Function in prostate cancer cells causes chemo-and radio-resistance and promotes tumor growth. Mol Cancer Ther 2010; 9: 336-46.
34. Singh A, Boldin-Adamsky S Thimmulappa RK. RNAi-mediated silencing of nuclear factor eruthroi-2-related factor 2 gene expression in non-small cell lung cancer inhibit tumor growth and increases efficacy of chemotherapy. Cancer Res 2008; 69: 7975-84.
35. Ma Y, Chan CY, Ming-Liang He. RNA interference and antiviral therapy, World J Gastroenterol 2007; 13: 5169-9.
36. Tan FL, Yin JQ. RNAi, a new therapeutic strategy against viral infection. Cell Res 2004; 14: 460-6.
37. Guo H, Gao J, Wu X. Toll-like receptor 2 siRNA suppresses corneal inflammation and attenuates Aspergillus fumigatus keratitis in rats. Immunol Cell Biol 2011; 1-6.
38. Dessy A, Gorman JM. The emerging therapeutic role of rnainterference in disorders of the central nervous system. Clin Pharmacol Ther 2011; 89: 450-4.
39. Burnett JC, Rossi JJ, Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J 2011; 6: 1130-46.
40. Watts JK, Corey DR. Clinical status of duplex RNA. Bioorg Med Chem Lett 2010; 20: 3203-07.
41. Tang G. siRNA and miRNA: an insight into RISCs. Trends Biochem Sci 2005; 30: 106-14.
42. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kB by Toll-like receptor 3. Nature 2001; 413: 732-8.
43. Dykxhoorn DM, Palliser D, Lieberman J. The silent treatment: siRNAs as small molecule drugs. Gene Ther 2006; 13: 541-52.
44. Judge AD, Sood, Shaw JR, Fang D, McClintock K, MacLachian I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol 2005; 23: 457-62.
45. Read ML, Mir S, Spice R. Profiling RNA interference (RNAi)-mediated toxicity in neural cultures for effective short interfering RNA design. J Gene Med 2009; 11: 523-34.
46. Karikó K, Bhuyan P, Capodici J, Weissman D. Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through Toll-Like Receptor 3. J Immunol 2004; 172: 6545-9.
47. Kleinman ME, Yamada K, Takeda A. et al. Sequence-and targetindependent angiogenesis suppression by siRNA via TLR3. Nature 2008; 452: 591-7.
48. Marques JT, Williams BR. Activation of the mammalian immune system by siRNAs. Nat Biotechnol 2005; 23:1399-405.
49. Rappaport J, Hanss B, Koop JB, et al. Transport of phosphorothioate oligonucleotides in kidney: implications for molecular therapy. Kidney Int 1995; 47: 1462-9.
50. Trehan S, Sharma G, Misra A. siRNA: Sojourn from discovery to delivery challenges and clinics. Syst Rev Pharm 2010; 1: 1-16.
51. Lin X, Ruan X, Anderson MG, et al. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res 2005; 33: 4527-35.
52. Jackson AL, Bartz S, Schelter J, Expression profile reveals offtarget gene regulation by RNAi. Nature 2003; 21: 635-7.
53. Semizarov F, Frost L, Sarthy A, Kroeger P, Halbert DN, Fesik SW. Specificity of short interfering RNA determined through gene expression signatures. Proc Natl Acad Sci 2003; 27: 6347-52.
54. Persengiev SP, Zhu X, Green MR. Nonspecific, concentrationdependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs). RNA 2004, 10: 12-8.
55. P. Lim LP, C. Lau NC, Garrett-Engele P, et al. Microarray analysis shows that some microRNAs down regulate large numbers of target mRNAs. Nature 2005; 433: 769-73.
56. Snøve O JR, Rossi JJ. Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi. Genome Bio 2006; 7: 231-36.
57. Burchard J, Jackson AL, Malkov V, et al. MicroRNA-like offtarget transcript regulation by siRNAs is species specific. RNA 2009; 15: 308-15.
58. Khalil IA, Kogure K, Akita H, Harashima H. Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev 2006; 58: 32-45.
59. Yoshimura T, Shono M, Imai K, HongK. Kinetic analysis of endocytosis and intracellular fate of liposomes in single macrophages. J Biochem 1995; 117: 34-41.
60. Sledz CA, Williams BR. RNA interference in biology and disease. Blood 2005; 106: 787-94.
61. Allison HS, Hall AH, Wan J, Shaughnessy EE, Ramsay Shaw B, Alexander KA. RNA interference using boranophosphate siRNAs: structure-activity relationships. Nucleic Acids Res 2004; 32: 5991-6000.
62. Amarzguioui M, Holen T, Babaie E, Prydz H. Tolerance for mutations and chemical modifications in a siRNA. Nucleic Acids Res 2003; 31: 589-95.
63. Harborth J, Elbashie SM, Vandenburgh K, et al. Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev 2003; 13: 83-105.
64. Braasch DA, Jensen S, Liu Y, et al. RNA Interference in Mammalian Cells by Chemically-Modified RNA. Biochemistry 2003; 42: 7967-75.
65. Bartlett DW, Davis ME. Insights into the kinetics of siRNAmediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucleic Acids Res 2006; 34: 322-33.
66. Allerson CR, Sioufi, N, Jarres R. Fully 2α-Modified Oligonucleotide Duplexes with Improved in Vitro Potency and Stability Compared to Unmodified Small Interfering RNA. J. Med. Chem 2005; 48: 901-04.
67. Layzer JM, Mccaffrey AP, Tanner AK, et al. In vivo activity of nuclease-resistant siRNAs. RNA 2004; 10: 766-71.
68. Czauderna F, Fechtner M, Dames S, et al. Structural variations and stabilising modify cations of synthetic siRNAs in mammalian cells. Nucleic Acids Res 2003; 31: 2705-16.
69. Lin Chiu Y, Rana TM. siRNA function in RNAi: A chemical modification analysis. RNA 2003; 9: 1034-48.
70. Hamm S, Latz E, Hangel D, et al. Alternating 2'-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist. Immunobiology 2010; 215: 559-69.
71. Elmen J, Thonberg H, Ljungberg K, et al. Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality. Nucleic Acids Res 2005; 33:439-47.
72. Grunweller A, Eliza Wyszko, Bieber B, Jahnel R, Erdmann VA, Kurreck J. Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2'-O-methyl RNA, phosphorothioates and small interfering RNA. Nucleic Acids Res 2003; 31: 3185-93.
73. Yamato K, Egawa N, Endo S. Enhanced specificity of HPV16 E6E7 siRNA by RNA-DNA chimera modification. Cancer Gene Ther 2011; 18: 587-97.
74. Wang J, Lu Z, Wientjes MG, Au JL. Delivery of siRNA Therapeutics: Barriers and Carriers. AAPSJ 2010; 12: 492-503.
75. Kanasty RL, Whitehead KA, Vegas AJ, Anderson DG. Action and Reaction: The Biological Response to siRNA and Its Delivery Vehicles. Mol Ther 2012; 20: 513-24.
76. Akhtar S, Benter IF. Nonviral delivery of synthetic siRNAs in vivo. J. Clin. Invest 2007; 117: 3623-32.
77. Stewart SA, Dykxhoorn DM, Palliser D. et al. Lentivirus-delivered stable gene silencing by RNAi in primary cells. RNA 2003; 9: 493-501.
78. Singer O, Verma IM. Applications of lentiviral vectors for shRNA delivery and transgenesis. Curr Gene Ther 2008; 8: 483-8.
79. Yi Y, Noh MJ, Lee KH. Current advances in retroviral gene therapy. Curr Gene Ther 2011; 11: 218-28.
80. Reeti Khare, Christopher Y Chen, Eric A Weaver, Michael A Barry. Advances and Future Challenges in Adenoviral Vector Pharmacology and Targeting. Curr Gene Ther 2011; 11: 241-258.
81. Mingozzi F, High KA. Immune Responses to AAV in Clinical Trials. Curr Gene Ther 2007; 7: 316-24.
82. Barton GM, Medzhitov R. Retroviral delivery of small interfering RNA into primary cells. Proc Natl Acad Sci 2002; 99: 14943-45.
83. Raper SE, Chirmule N, Lee FS, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient pa tient following adenoviral gene transfer. Mol Genet Metlab 2003; 80: 148-158.
84. Hacein-Bey-Abina S, von Kalle C, Schmidt M. et al. Serious Adverse Event after Successful Gene Therapy for X-Linked Severe Combined Immunodeficiency. N Engl J Med 2003; 349: 255-6.
85. Khurana B, Goyal AK, Budhiraja A, Arora D, Vyas SP. siRNA delivery using nanocarriers-an efficient tool for gene silencing. Curr Gene Ther 2010; 10: 139-55.
86. Patil Y, Panyam J, Polymeric nanoparticles for siRNA delivery and gene silencing. Int L Pharm 2009; 367: 195-203.
87. Lee SY, Huh MS, Lee S, et al. Stability and cellular uptake of polymerized siRNA (poly-siRNA)/polyethylenimine (PEI) complexes for efficient gene silencing. J Control Release 2010; 141: 339-46.
88. Beyerle A, Braun A, Merkel O, et al. Comparative in vivo study of poly(ethylene imine)/siRNA complexes for pulmonary delivery in mice. J Control Release 2011; 151: 51-6.
89. Ward CM, Read ML, Seymou LW. Systemic circulation of poly(L-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy. Blood 2001; 15: 2221-29.
90. Lee H, Jeong JH, Park TG. PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity. J Control Release 2002; 79: 283-91.
91. Choi YS, Lee JY, Suh JS, et al. The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine. Biomaterials 2010; 31: 1429-43.
92. Nam HY, Kim J, Kim S, et al. Cell penetrating peptide conjugated bio reducible polymer for si RNA delivery. Biomaterials 2011; 32: 5213-22.
93. Noh SM, Myung Ok Park MO, Shim G. Pegylated poly-L-arginine derivatives of chitosan for effective delivery of siRNA. J Control Release 2010; 145: 159-64.
94. de Martimprey H, Jean-Remi Bertrand JR, Fusco A, et al. siRNA nanoformulation against the Ret/PTC1junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Res 2008; 36:e2.
95. Ma Z, Li J, He F. Cationic lipids enhance siRNA-mediated interferon response in mice. Biochem Biophys Res Commun 2005; 13: 755-9.
96. Kenny GD, Kamaly N, Kalber et al. Novel multifunctional nanoparticle mediates siRNA tumour Nazila delivery, and therapeutic tumour reduction in vivo. J control Release 2011; 149: 111-6.
97. Zintchenko A, Philipp A, Dehshahri A, Wagner E. Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity. Bioconjug Chem 2008; 19: 1448-55.
98. Du J, Sun Y, Shi QS, et al. Biodegradable Nanoparticles of mPEGPLGA-PLL Triblock Copolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing. Int J Mol Sci. 2012; 13: 516-33.
99. Liu P, Yu H, Sun Y, Zhu M, Duan Y. A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery. Biomaterials 2012; 33: 4403-12.
100. Boe SL, Longva AS, Hoyig E. Cyclodextrin-containing polymer delivery system for light-directed siRNA gene silencing. Oligonucleotides 2010; 20:175-82.
101. Tong H, Qin S, Fernandes JC, Li L, Dai K, Zhang X. Progress and prospects of chitosan and its derivatives as non-viral gene vectors in gene therapy. Curr Gene Ther 2009; 9: 495-502.
102. Techaarpornkul S, Wongkupasert S, Opanasopit P, Apirakaramwong A, Nunthanid J, Ruktanonchai U. Chitosan-Mediated siRNA Delivery In Vitro: Effect of Polymer Molecular Weight, Concentration and Salt Forms. AAPS PharmSciTech 2010; 11: 64-72.
103. Tahara K, Yamamoto H, Hirashima N, Kawashima Y. Chitosanmodified poly(D, L-lactide-co-glycolide) nanospheres for improving siRNA delivery and gene-silencing effects. Eur J Pharm Biopharm 2010; 74: 421-6.
104. Rothdiener M, Müller D, Castro PG, et al. Targeted delivery of SiRNA to CD33-positive tumor cells with liposomal carrier systems. J Control Release 2010; 144: 251-8.
105. Hatakeyama H, Ito E, Akita H, et al. A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J Control Release 2009; 139:127-32.
106. Maurer N, Wong, KF, Stark H. Spontaneous entrapment of polynucleotides upon electrostatic interaction with ethanol-destabilized cationic liposomes. Biophys J 2001; 80: 2310-26.
107. Regelin AE, Fankhaenel S, Gurtesch L, et al. Biophysical and lipofection studies of DOTAP analogs. Biochem Biophys Acta 2000; 15: 151-64.
108. Ross PC, Hui SW, Lipoplex size is a major determinant of in vitro lipofection efficiency. Gene Ther 1999; 6: 651-9.
109. Mufamadi MS, Pillay V, Choonara YE, et al. A review on composite liposomal technologies for specialized drug delivery. J Drud Deliv 2011; 2011:1-19.
110. Ramezani M, Majid Khoshhamdam M, Dehshahri A, Bizhan Malaekeh-Nikouei B. The influence of size, lipid composition and bilayer fluidity of cationic liposomes on the transfection efficiency of nanolipoplexes. Colloids Surf B Biointerfaces 2009; 72: 1-5.
111. Foged C, Nielsen HM, Frokjaer S. Liposomes for phospholipase A 2 triggered siRNA release: preparation andin vitro test. Int J Pharm 2007; 331: 160-6.
112. Montier T, Benvegnu T, Jaffrès PA, Yaouanc JJ, Lehn P. Progress in Cationic Lipid-Mediated Gene Transfection: A Series of Bio-Inspired Lipids as an Example. Curr Gene Ther 2008; 8: 296-312.
113. Ewert KK, Zidovska A, Ahmad A, et al. Cationic Liposome-Nucleic Acid Complexes for Gene Delivery and Silencing: Pathways and Mechanisms for Plasmid DNA and siRNA. Top Curr Chem 2010; 296: 191-226.
114. Gao L, Sun J Huimei Li H, et al. Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene silencing. Biomaterials 2010; 31: 2655-64.
115. The role of dioleoylphosphatidylethanolamine (DOPE) in targeted gene delivery with mannosylated cationic liposomes via intravenous route. J Control Release 2005; 108: 484-95.
116. Zuhorn IS, Bakowsky U, Polushkin E, et al. Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection Efficiency. Mol Ther 2005; 11: 801-10.
117. Arthanari Y, Pluen A, Rajendran A, Aojula H, Demonacos C. Delivery of therapeutic shRNA and siRNA by Tat fusion peptide targeting bcr-abl fusion gene in Chronic Myeloid Leukemia cells. J control Release 2010; 145: 272-80.
118. Zhang C, Ning Tang N, Liu X, et al. siRNA-containing liposomes modified with polyarginine effectively silence the targeted gene J Control Release 2006; 112: 229-39.
119. Akita H, Kogure K, MoriguchiR, et al. Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: programmed endosomal escape and dissociation. J Control Release 2010; 143: 111-7.
120. Shim GY, Kim SH, Han SF, Kim YB, Oh YK. Cationic surfactin liposomes for enhanced cellular delivery of siRNA. Asian J Pharm Sci 2009, 4: 207-14.
121. Kitamato D, Isoda H, Nakhara T, Function and potential application of glycolipid bisurfactant from energy saving Material to gene delivery carriers. J Biosci Bioeng 2002; 94: 187-201.
122. Zuhorn IS, Engberts JB, Hoekstra D. et al. Gene delivery by cationic lipid vectors: overcoming cellular barriers. Eur Biophys J 2007; 36: 349-362.
123. Semple SC, Akinc A, Chen J, Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 2010; 28: 172-8.
124. Liu Y, Huang L, Designer Lipids Advance Systemic siRNA Delivery. Mol Ther 2010; 18: 669-70.
125. 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: 1222-34.
126. Manuela Aleku M, Schulz P, Keil O, et al. Atu027, a Liposomal Small Interfering RNA Form Protein Kinase N3, Inhibits Cancer Progression. Cancer Res 2008; 68: 9788-98.
127. Akinc A, Goldberg M, Qin J, Development of Lipidoid-siRNA Formulations for Systemic Delivery to the Liver. Mol Ther 2009; 17: 872-9.
128. Schlegel A, Largeau C, Bigey P, et al. Anionic polymers for decreased toxicity and enhancedin vivo delivery of siRNA complexed with cationic liposomes. J Control Release 2011; 152: 393-401.
129. Okayama R, Noji M, Nakanishi M, Cationic cholesterol with a hydroxyethylamino head group promotes significantly liposomemediated gene transfection. FEBS Lett 1997; 408: 232-34.
130. Remy JS, Kicher A, Mardviniv V, Achuber F, Behr JP, Targeted gene transferrin to hepatoma cells with lipopolyamine condensed DNA particles presenting galactose ligands:A stage toward artificial viruses. Proc Nat Acad Sci 1995; 92: 1744-48.
131. Huang QD, Zhong GX, Zhang Y, Cyclen-based cationic lipids for highly efficient Gene delivery towards tumor cells. Plose One 2011; 6: e23134.
132. Tang F, Hughes JA. Synthesis of a single-tailed cationic lipid and investigation of its transfection. J Control Release 1999; 62: 345-58.
133. Filion MC, Phillips NC. Major limitations in the use of cationic liposomes for DNA delivery. Int J Pharm 1998; 162:159-70.
134. Filion MC, Phillips NC, Anti-inflammatory activity of cationic lipids. Br J Phamacol 1997; 122: 551-7.
135. Filion MC, Phillips NC, Toxicity and immunomodulatory activity of liposomal vectors formulated with cationic lipids toward immune effector cells. Biochim Biophys Acta 1997; 1329: 345-56.
136. Nuzzo F, Sala F, Biondi O, et al. Liposomes Induce Chromosome Aberrations in Human Cultured Cells, Exp Cell Res 1995; 157: 397-408.
137. Chonn A, Cullis P, Devine DV. The role of surface charge in the activation of classical and alternative pathways of complement by liposomes. J Immunol 1991; 146: 4234-41.
138. Hornung V, Guenthner-Biller M, Bourquin C, et al. Sequencespecific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 2005; 11: 263-70.
139. Spagnou S, Miller AD, Keller M. Lipidic Carriers of siRNA: differences in the formulation, cellular uptake, and delivery with plasmid DNA. Biochemistry 2004; 43: 13348-56.
140. Landen CN Jr, Chavez-Reyes A, Bucana C, et al. Therapeutic EphA2 Gene in vivo targeting Using neutral liposomal small interfering RNA delivery. Cancer Res 2005; 65: 6910-18.
141. Hattori Y, Maitani Y, Folate linked nanoparticle mediated suicide gene therapy in human prostate cancer and nasopharyngeal cancer with herpes simplex virus thymidine kinase. Cancer Gene Ther 2005; 12: 769-809.
142. Akinc A, William Querbes W, De S. Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms. Mol Ther 2010; 18: 1357-64.
143. Watanabe T, Umehara T, Fumihiko Yasui F, et al. Liver target delivery of small interfering RNA to the HCV gene by lactosylated cationic liposome. J Hepatol 2007; 47: 744-50.
144. Ishida T, Harada M, Wang XY et al. Accelerated blood clearance of PEGylated liposomes following preceding liposome injection: Effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. J Control Release 2005; 105: 305-17.
145. Henriques AM, Madeira C, Fevereiro M, et al. Effect of cationic liposomes/DNA charge ratio on gene expression and antibody response of a candidate DNA vaccine against Maedi Visna virus. Int J Pharm 2009; 377: 92-8.
146. 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: 184-94.
147. Harmon AM, Lash MH,. Sparks SM, Uhrich KE, Preferential cellular uptake of amphiphilic macromolecule lipid complexes with enhanced stability and biocompatibility, J Control Release 2011; 153: 233-39.
148. Han SE, Kang H, Shim GY, Novel cationic cholesterol derivativebased liposomes for serum-enhanced delivery of siRNA. Int J Pharm 2008; 353: 260-9.
149. Liu L, Zern MA, Lizarzaburu ME, Nantz MH, Wu J. Poly(cationic lipid)-mediated in vivo gene delivery to mouse liver. Gene Ther 2003; 10: 180-7.
150. Klein E, Leborgne C, Ciobanu M, et al. Nucleic acid transfer with hemifluorinated polycationic lipids. Biomaterials 2010; 31: 4781-88.
151. Dileep PV, Antony A, Bhattacharya S. Incorporation of oxyethylene units between hydrocarbon chain and pseudoglyceryl backbone in cationic lipid potentiates gene transfection effciency in the presence of serum. FEBS Lett 2001; 509: 327-31.
152. Yingyongnarongkul B, Radchatawedchakoon W, Krajarng A, Watanapokasin R, Suksamrarn A. High transfection efficiency and low toxicity cationic lipids with aminoglycerol-diamine conjugate. Bioorg Med Chem 2009; 17: 176-88.
153. Lee RJ, Huang L. Folate-targeted, anionic liposome-entrapped polylysine-condensed DNA for tumor cell-specific gene transfer. J Biol Chem 1996; 271: 8481-87.
154. Guo W, Lee RJ. Efficient gene delivery using anionic liposomecomplexed polyplexes (LPDII). Biosci Rep 2000; 20: 419-32.
155. Movassaghian S, Moghimi HR, Shirazi FH, Torchilin VP. Dendrosome-dendriplex inside liposomes: as a gene delivery system. J Drug Target 2011; 19: 925-32.
156. Davidson BL, McCray Jr PB. Current prospects for RNA interference-based therapies. Nat Rev Genet 2011; 12: 329-40.
157. Judge AD, Robbins M, Tavakoli, I, et al. Confirming the RNAimediated mechanism of action of siRNA-based cancer therapeutics in mice. J Clin Invest 2009; 119: 661-73.
158. Lee KS, Yuan YL, Kuriyama R, Erikson RL. Plk is an M-phasespecific protein kinase and interacts with a kinesin-like protein, CHO1/MKLP-1. Mol Cell Biol 1995; 15: 7143-51.
159. Lenar P, Petronczki M, Steeg-maier M. The small-molecule inhibitor BI 2536 reveals novel insights into mitotic roles of polo-like kinase 1. Curr Biol 2007; 17: 304-15.
160. Glover DM, Hagan IM, Tavares AA. Polo-like kinases: a team that plays throughout mitosis. Genes Dev 1998; 12: 3777-87.
161. Sumara I, Gimenez-Abian JF, Gerlich D, et al. Roles of Polo-like Kinase 1 in the Assembly of Functional Mitotic Spindles. Current Biology 2004;14:1712-22.
162. Ito Y, Miyoshi E, Sasaki N, et al. Polo-like kinase 1 overexpression is an early event in the progression of papillary carcinoma. Br J Cancer 2004; 90: 414-8.
163. Takahashi T, Sano B, Nagata T, et al. Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers. Cancer Sci 2003; 94: 148-52.
164. Weichert W, Ullrich A, Schmidt M, et al. Expression patterns of polo-like kinase 1 in human gastric cancer. Cancer Sci 200; 97: 271-6.
165. Renner AG, Dos Santos C, Recher C, et al. Polo-like kinase 1 is overexpressed in acute myeloid leukemia and its inhibition preferentially targets the proliferation of leukemic cells. Blood 2009; 114: 659-62.
166. Spankuch-Schmitt B, Bereiter-Hahn J, Kaufmann M, Strebhardt K. Effect of RNA Silencing of Polo-Like Kinase-1 (PLK1) on Apoptosis and Spindle Formation in Human Cancer Cells. J Natl Cancer Inst 2002; 94: 1863-77.
167. Reagan-Shaw S, Ahmad N. Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer. FASEB J 2005; 19: 611-3.
168. Vaishnaw AK, Gollob J, Gamba-Vitalo C, et al. A status report on RNAi therapeutics. Silence 2010; 1: 1-14.
169. http://www.alnylam.com/index.php June 2011.
170. http://silence-therapeutics.com/content/newsandevents/stories/2011/release_060611.pdf
171. Koldehoff M, Steckel NK, Beelen DW, Elmaagacli AH. Therapeutic application of small interfering RNA directed against bcr-abl transcripts to a patient with imatinib-resistant chronic myeloid leukaemia. Clin Exp Med 2007; 7: 47-55.