In vivo safety and antitumor efficacy of bifunctional small hairpin RNAs specific for the human stathmin 1 oncoprotein

DNA and Cell Biology

Volumn 30, Issue 9, 2011, Pages 715-726

  Phadke, Anagha P ^a   Jay, Chris M ^a   Wang, Zhaohui ^a   Chen, Salina ^a   Liu, Shengnan ^a,b   Haddock, Courtney ^a   Kumar, Padmasini ^a   Pappen, Beena O ^a   Rao, Donald D ^a   Templeton, Nancy S ^a   Daniels, Egeenee Q ^c   Webb, Craig ^d   Monsma, David ^d   Scott, Stephanie ^d   Dylewski, Dawna ^d   Frieboes, Hermann B ^e   Brunicardi, Francis Charles ^f   Senzer, Neil ^a,b,g,h   Maples, Phillip B ^a   Nemunaitis, John ^a,b,g,h   Tong, Alex W ^a   more..

^a GRADALIS INC   (United States)

^b BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

^c UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER   (United States)

^d VAN ANDEL RESEARCH INSTITUTE   (United States)

^e University of Louisville   (United States)

^f BAYLOR COLLEGE OF MEDICINE   (United States)

^g Mary Crowley Cancer Research Centers   (United States)

^h TEXAS ONCOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2 DIOLEOYL 3 TRIMETHYLAMMONIOPROPANE; ANTINEOPLASTIC AGENT; CHOLESTEROL; LIPOSOME; MICRORNA; PLASMID BIFUNCTIONAL SHORT HAIRPIN RNA STATHMIN 1; SHORT HAIRPIN RNA; STATHMIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CANCER INHIBITION; COLORECTAL CANCER; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; FEMALE; GENE EXPRESSION; GENETIC CODE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOCOMPETENCE; IN VITRO STUDY; IN VIVO STUDY; MALE; MAXIMUM TOLERATED DOSE; MELANOMA; MELANOMA CELL; MOUSE; NONHUMAN; NUDE MOUSE; OSTEOSARCOMA; PRIORITY JOURNAL; PROGNOSIS; RAT; RNA INTERFERENCE; SINGLE DRUG DOSE; SOLID TUMOR; TUMOR XENOGRAFT;

ANIMALS; COLORECTAL NEOPLASMS; DNA PRIMERS; FEMALE; GENE KNOCKDOWN TECHNIQUES; GENE THERAPY; HUMANS; IMMUNOBLOTTING; MALE; MAXIMUM TOLERATED DOSE; MELANOMA; MICE; MICE, NUDE; RATS; RATS, SPRAGUE-DAWLEY; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; RNA, SMALL INTERFERING; STATHMIN;

MUS; RATTUS;

EID: 80053542062     PISSN: 10445498     EISSN: 15577430     Source Type: Journal    
DOI: 10.1089/dna.2011.1240     Document Type: Article

References (68)

1. Abrams, M.T., Koser, M.L., Seitzer, J., Williams, S.C., DiPietro, M.A., Wang, W., Shaw, A.W., Mao, X., Jadhav, V., Davide, J.P., Burke, P.A., Sachs, A.B., Stirdivant, S.M., and Sepp-Lor- enzino, L. (2010). Evaluation of efficacy, biodistribution, and inflammation for a potent siRNA nanoparticle: effect of dexamethasone co-treatment. Mol Ther 18, 171-180.
2. Alli, E., Bash-Babula, J., Yang, J.M., and Hait, W.N. (2002). Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer. Cancer Res 62, 6864-6869. (Pubitemid 35424074)
3. Alli, E., Yang, J.M., Ford, J.M., and Hait, W.N. (2007a). Reversal of stathmin-mediated resistance to paclitaxel and vinblastine in human breast carcinoma cells. Mol Pharmacol 71, 12331240. (Pubitemid 46658676)
4. Alli, E., Yang, J.M., and Hait, W.N. (2007b). Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. Oncogene 26, 1003-1012.
5. Ashihara, E., Kawata, E., and Maekawa, T. (2009). Future prospect of RNA interference for cancer therapies. Curr Drug Targets 50, 1577-1588.
6. Bartek, J., Iggo, R., Gannon, J., and Lane, D.P. (1990). Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines. Oncogene 5, 893-899.
7. Belletti, B., Nicoloso, M.S., Schiappacassi, M., Berton, S., Lovat, F., Wolf, K., Canzonieri, V., D'Andrea, S., Zucchetto, A., Friedl, P., Colombatti, A., and Baldassarre, G. (2008). Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. Mol Biol Cell 19, 2003-2013.
8. Carney, B.K., and Cassimeris, L. (2010). Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53. Cancer Biol Ther 9, 699-709.
9. Chen, C., Ridzon, D.A., Broomer, A.J., Zhou, Z., Lee, D.H., Nguyen, J.T., Barbisin, M., Xu, N.L., Mahuvakar, V.R., Andersen, M.R., Lao, K.Q., Livak, K.J., and Guegler, K.J. (2005). Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33, e179.
10. Clark, P.R., Stopeck, A.T., Ferrari, M., Parker, S.E., and Hersh, E.M. (2000). Studies of direct intratumoral gene transfer using cationic lipid-complexed plasmid DNA. Cancer Gene Ther 7, 853-860. (Pubitemid 30437285)
11. Clauser, K.R., Hall, S.C., Smith, D.M., Webb, J.W., Andrews, L.E., Tran, H.M., Epstein, L.B., and Burlingame, A.L. (1995). Rapid mass spectrometric peptide sequencing and mass matching for characterization of human melanoma proteins isolated by two-dimensional PAGE. Proc Natl Acad Sci USA 92, 5072-5076.
12. Ding, L., Ellis, M.J., Li, S., Larson, D.E., Chen, K., Wallis, J.W., Harris, C.C., McLellan, M.D., Fulton, R.S., Fulton, L.L., Abbott, R.M., Hoog, J., Dooling, D.J., Koboldt, D.C., Schmidt, H., Kalicki, J., Zhang, Q., Chen, L., Lin, L., Wendl, M.C., McMichael, J.F., Magrini, V.J., Cook, L., McGrath, S.D., Vickery, T.L., Appelbaum, E., Deschryver, K., Davies, S., Guintoli, T., Crowder, R., Tao, Y., Snider, J.E., Smith, S.M., Dukes, A.F., Sanderson, G.E., Pohl, C.S., Delehaunty, K.D., Fronick, C.C., Pape, K.A., Reed, J.S., Robinson, J.S., Hodges, J.S., Schierding, W., Dees, N.D., Shen, D., Locke, D.P., Wiechert, M.E., Eldred, J.M., Peck, J.B., Oberkfell, B.J., Lolofie, J.T., Du, F., Hawkins, A.E., O'Laughlin, M.D., Bernard, K.E., Cunningham, M., Elliott, G., Mason, M.D., Thompson, D.M., Jr., Ivanovich, J.L., Goodfellow, P.J., Perou, C.M., Weinstock, G.M., Aft, R., Watson, M., Ley, T.J., Wilson, R.K., and Mardis, E.R. (2010). Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464, 999-1005.
13. Fu, X., Guadagni, F., and Hoffman, R.M. (1992). A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens. Proc Natl Acad Sci USA 89, 5645-5649.
14. Gan, L., Guo, K., Li, Y., Kang, X., Sun, L., Shu, H., and Liu, Y. (2010). Up-regulated expression of stathmin may be associated with hepatocarcinogenesis. Oncol Rep 23, 1037-1043.
15. Girnita, L., Girnita, A., Brodin, B., Xie, Y., Nilsson, G., Dricu, A., Lundeberg, J., Wejde, J., Bartolazzi, A., Wiman, K.G., and Larsson, O. (2000). Increased expression of insulin-like growth factor I receptor in malignant cells expressing aberrant p53: functional impact. Cancer Res 60, 5278-5283.
16. Hsieh, S.Y., Huang, S.F., Yu, M.C., Yeh, T.S., Chen, T.C., Lin, Y.J., Chang, C.J., Sung, C.M., Lee, Y.L., and Hsu, C.Y. (2010). Stathmin1 overexpression associated with polyploidy, tumor- cell invasion, early recurrence, and poor prognosis in human hepatoma. Mol Carcinog 49, 476-487.
17. Huang, Y.H., Bao, Y., Peng, W., Goldberg, M., Love, K., Bum-crot, D.A., Cole, G., Langer, R., Anderson, D.G., and Sawicki, J.A. (2009). Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis. Proc Natl Acad Sci USA 106, 3426-3430.
18. Iancu, C., Mistry, S.J., Arkin, S., and Atweh, G.F. (2000). Taxol and anti-stathmin therapy: a synergistic combination that targets the mitotic spindle. Cancer Res 60, 3537-3541. (Pubitemid 30482174)
19. Ito, I., Ji, L., Tanaka, F., Saito, Y., Gopalan, B., Branch, C.D., Xu, K., Atkinson, E.N., Bekele, B.N., Stephens, L.C., Minna, J.D., Roth, J.A., and Ramesh, R. (2004). Liposomal vector mediated delivery of the 3p FUS1 gene demonstrates potent antitumor activity against human lung cancer in vivo. Cancer Gene Ther 11, 733-739. (Pubitemid 39488471)
20. Jay, C., Nemunaitis, G., Nemunaitis, J., Senzer, N., Hinderlich, S., Darvish, D., Ogden, J., Eager, J., Tong, A., and Maples, P. (2008). Preclinical assessment of wt GNE gene plasmid for management of hereditary inclusion body myopathy 2 (HIBM2). Gene Regul Syst Bio 2, 243-252.
21. Jeon, T.Y., Han, M.E., Lee, Y.W., Lee, Y.S., Kim, G.H., Song, G.A., Hur, G.Y., Kim, J.Y., Kim, H.J., Yoon, S., Baek, S.Y., Kim, B.S., Kim, J.B., and Oh, S.O. (2010). Overexpression of stath-min1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer 102, 710-718.
22. Jiang, L., Chen, Y., Chan, C.Y., Wang, X., Lin, L., He, M.L., Lin, M.C., Yew, D.T., Sung, J.J., Li, J.C., and Kung, H.F. (2009). Down-regulation of stathmin is required for TGF-beta induc- ible early gene 1 induced growth inhibition of pancreatic cancer cells. Cancer Lett 274, 101-108.
23. Kang, Y., Zhang, X., Jiang, W., Wu, C., Chen, C., Zheng, Y., Gu, J., and Xu, C. (2009). Tumor-directed gene therapy in mice using a composite nonviral gene delivery system consisting of the pig- gyBac transposon and polyethylenimine. BMC Cancer 9, 126.
24. Lagos-Quintana, M., Rauhut, R., Meyer, J., Borkhardt, A., and Tuschl, T. (2003). New microRNAs from mouse and human. RNA 9, 175-179. (Pubitemid 36206285)
25. Lee, Y., Kim, M., Han, J., Yeom, K.H., Lee, S., Baek, S.H., and Kim, V.N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23, 4051-4060. (Pubitemid 39472426)
26. Li, S., Dong, W., Zong, Y., Yin, W., Jin, G., Hu, Q., Huang, X., Jiang, W., and Hua, Z.C. (2007). Polyethylenimine-complexed plasmid particles targeting focal adhesion kinase function as melanoma tumor therapeutics. Mol Ther 15, 515-523.
27. Liu, S., Ballian, N., Belaguli, N.S., Patel, S., Li, M., Templeton, N.S., Gingras, M.C., Gibbs, R., Fisher, W., and Brunicardi, F.C. (2008). PDX-1 acts as a potential molecular target for treatment of human pancreatic cancer. Pancreas 37, 210-220.
28. Liu, Y., and Bodmer, W.F. (2006). Analysis of P53 mutations and their expression in 56 colorectal cancer cell lines. Proc Natl Acad Sci USA 103, 976-981. (Pubitemid 43212207)
29. Lopez-Barcons, L.A. (2009). Small-cell neuroendocrine carcinoma of the prostate: are heterotransplants a better experimental model? Asian J Androl 12, 308-314.
30. Lu, C., Sepulveda, C.A., Ji, L., Ramesh, R., O'Connor, S., Jaya- chandran, G., Hicks, M.E., Munden, R.F., Lee, J.J., Templeton, N.S., McMannis, J.D., Stewart, D.J., and Roth, J.A. (2007). Systemic therapy with tumor suppressor FUS1-nanoparticles for stage IV lung cancer. In Annual AACR Meeting. Los Angeles, CA.
31. Mistry, S.J., and Atweh, G.F. (2002). Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. Mt Sinai J Med 69, 299-304. (Pubitemid 35244131)
32. Mistry, S.J., and Atweh, G.F. (2006). Therapeutic interactions between stathmin inhibition and chemotherapeutic agents inprostate cancer. Mol Cancer Ther 5, 3248-3257. (Pubitemid 46092068)
33. Mistry, S.J., Bank, A., and Atweh, G.F. (2007). Synergistic anti-angiogenic effects of stathmin inhibition and taxol exposure. Mol Cancer Res 5, 773-782. (Pubitemid 47294805)
34. Nemunaitis, G., Maples, P.B., Jay, C., Gahl, W.A., Huizing, M., Poling, J., Tong, A.W., Phadke, A.P., Pappen, B.O., Bedell, C., Templeton, N.S., Kuhn, J., Senzer, N., and Nemunaitis, J. (2010). Hereditary inclusion body myopathy: single patient response to GNE gene Lipoplex therapy. J Gene Med 12, 403412.
35. Nemunaitis, J., Senzer, N., Khalil, I., Shen, Y., Kumar, P., Tong, A., Kuhn, J., Lamont, J., Nemunaitis, M., Rao, D., Zhang, Y.A., Zhou, Y., Vorhies, J., Maples, P., Hill C., and Shanahan, D. (2007). Proof concept for clinical justification of network mapping for personalized cancer therapeutics. Cancer Gene Ther 14, 686-695. (Pubitemid 47080360)
36. Nomura, T., Nakajima, S., Kawabata, K., Yamashita, F., Taka- kura, Y., and Hashida, M. (1997). Intratumoral pharmacoki- netics and in vivo gene expression of naked plasmid DNA and its cationic liposome complexes after direct gene transfer. Cancer Res 57, 2681-2686. (Pubitemid 27283780)
37. Olivier, M., Petitjean, A., Marcel, V., Petre, A., Mounawar, M., Plymoth, A., de Fromentel, C.C., and Hainaut, P. (2009). Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 16, 1-12.
38. Perez-Soler, R., Kemp, B., Wu, Q.P., Mao, L., Gomez, J., Zele- niuch-Jacquotte, A., Yee, H., Lee, J.S., Jagirdar, J., and Ling, Y.H. (2000). Response and determinants of sensitivity to pac- litaxel in human non-small cell lung cancer tumors hetero- transplanted in nude mice. Clin Cancer Res 6, 4932-4938. (Pubitemid 32110439)
39. Phadke, A.P., Jay, C., Chen, S.J., Haddock, C., Wang, Z., Yu, Y., Nemunaitis, D., Nemunaitis, G., Templeton, N.S., Senzer, N., Maples, P.B., Tong, A.W., and Nemunaitis, J. (2009). Safety and in vivo expression of a GNE-transgene: a novel treatment approach for hereditary inclusion body myopathy-2. Gene Regul Syst Bio 3, 89-101.
40. Pille, J.Y., Denoyelle, C., Varet, J., Bertrand, J.R., Soria, J., Opo- lon, P., Lu, H., Pritchard, L.L., Vannier, J.P., Malvy, C., Soria, C., and Li, H. (2005). Anti-RhoA and anti-RhoC siRNAs inhibit the proliferation and invasiveness of MDA-MB-231 breast cancer cells in vitro and in vivo. Mol Ther 11, 267-274.
41. Pizzorno, M.C., O'Hare, P., Sha, L., LaFemina, R.L., and Hay- ward, G.S. (1988). Trans-activation and autoregulation of gene expression by the immediate-early region 2 gene products of human cytomegalovirus. J Virol 62, 1167-1179. (Pubitemid 18082930)
42. Ramesh, R., Saeki, T., Templeton, N.S., Ji, L., Stephens, L.C., Ito, I., Wilson, D.R., Wu, Z., Branch, C.D., Minna, J.D., and Roth, J.A. (2001). Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector. Mol Ther 3, 337-350. (Pubitemid 32514650)
43. Rana, S., Maples, P.B., Senzer, N., and Nemunaitis, J. (2008). Stathmin 1: a novel therapeutic target for anticancer activity. Expert Rev Anticancer Ther 8, 1461-1470.
44. Rao, D.D., Maples, P.B., Senzer, N., Kumar, P., Wang, Z., Pap-pen, B.O., Yu, Y., Haddock, C., Jay, C., Phadke, A.P., Chen, S., Kuhn, J., Dylewski, D., Scott, S., Monsma, D., Webb, C., Tong, A., Shanahan, D., and Nemunaitis, J. (2010). Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference. Cancer Gene Ther 17, 780-791.
45. Rao, D.D., Senzer, N., Cleary, M.A., and Nemunaitis, J. (2009). Comparative assessment of siRNA and shRNA off target effects: what is slowing clinical development. Cancer Gene Ther 16, 807-809.
46. Rayburn, E.R., and Zhang, R. (2008). Antisense, RNAi, and gene silencing strategies for therapy: mission possible or impossible? Drug Discov Today 13, 513-521.
47. Reid, T.R., Freeman, S., Post, L., McCormick, F., and Sze, D.Y. (2005). Effects of Onyx-015 among metastatic colorectal cancer patients that have failed prior treatment with 5-FU/leucov- orin. Cancer Gene Ther 12, 673-681. (Pubitemid 41045565)
48. Revheim, M.E., Seierstad, T., Berner, J.M., Bruland, O.S., Roe, K., Ohnstad, H.O., Bjerkehagen, B., and Bach-Gansmo, T. (2009). Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice. Anticancer Res 29, 4331-4336.
49. Rouleau, C., Menon, K., Boutin, P., Guyre, C., Yoshida, H., Ka- taoka, S., Perricone, M., Shankara, S., Frankel, A.E., Duesbery, N.S., Vande Woude, G., Biemann, H.P., and Teicher, B.A. (2008). The systemic administration of lethal toxin achieves a growth delay of human melanoma and neuroblastoma xenografts: assessment of receptor contribution. Int J Oncol 32, 739-748. (Pubitemid 351780584)
50. Rubin, C.I., and Atweh, G.F. (2004). The role of stathmin in the regulation of the cell cycle. J Cell Biochem 93, 242-250. (Pubitemid 44264202)
51. Ryschich, E., Huszty, G., Wentzensen, N., Schmidt, E., Knaebel, H.P., Encke, J., Marten, A., Buchler, M.W., and Schmidt, J. (2007). Effect of Flt3 ligand gene transfer in experimental pancreatic cancer. Int J Colorectal Dis 22, 215-223. (Pubitemid 44964025)
52. Shi, Q., Nguyen, A.T., Angell, Y., Deng, D., Na, C.R., Burgess, K., Roberts, D.D., Brunicardi, F.C., and Templeton, N.S. (2010). A combinatorial approach for targeted delivery using small molecules and reversible masking to bypass nonspecific uptake in vivo. Gene Ther 17, 1085-1097.
53. Simberg, D.W.A., and Barenholz, Y. (2005). Reversible mode of binding of serum proteins to DOTAP/cholesterol Lipoplexes: a possible explanation for intravenous lipofection efficiency. Hum Gene Ther 16, 1087-1096. (Pubitemid 41324568)
54. Sinek, J.P., Sanga, S., Zheng, X., Frieboes, H.B., Ferrari, M., and Cristini, V. (2009). Predicting drug pharmacokinetics and effect in vascularized tumors using computer simulation. J Math Biol 58, 485-510.
55. Templeton, N.S. (2002). Cationic liposome-mediated gene delivery in vivo. Biosci Rep 22, 283-295. (Pubitemid 35222736)
56. Templeton, N.S. (2009). Nonviral delivery for genomic therapy of cancer. World J Surg 33, 685-697.
57. Templeton, N.S., Lasic, D.D., Frederik, P.M., Strey, H.H., Roberts, D.D., and Pavlakis, G.N. (1997). Improved DNA: lipo- some complexes for increased systemic delivery and gene expression. Nat Biotechnol 15, 647-652. (Pubitemid 27291165)
58. Tong, A.W., Jay, C.M., Senzer, N., Maples, P.B., and Nemunaitis, J. (2009). Systemic therapeutic gene delivery for cancer: crafting Paris' arrow. Curr Gene Ther 9, 45-60.
59. Tsutsumi, K., Yamaura, T., Nakajima, M., Honda, T., and Ka- saoka, T. (2009). Silencing of focal adhesion kinase by tumor direct injection of small interfering RNA decreases in vivo tumor growth. Cancer Biol Ther 8, 1292-1299.
60. Vaishnaw, A.K., Gollob, J., Gamba-Vitalo, C., Hutabarat, R., Sah, D., Meyers, R., de Fougerolles, T., and Maraganore, J. (2010). A status report on RNAi therapeutics. Silence 1, 14.
61. Wang, R., Dong, K., Lin, F., Wang, X., Gao, P., Wei, S.H., Cheng, S.Y., and Zhang, H.Z. (2007). Inhibiting proliferation and enhancing chemosensitivity to taxanes in osteosarcoma cells by RNA interference-mediated downregulation of stathmin expression. Mol Med 13, 567-575. (Pubitemid 350228717)
62. Watters, D., Garrone, B., Coomer, J., Johnson, W.E., Brown, G., and Parsons, P. (1998). Stimulation of melanogenesis in a human melanoma cell line by bistratene A. Biochem Pharmacol 55, 1691-1699. (Pubitemid 28224492)
63. Wu, L., Fan, J., and Belasco, J.G. (2008). Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol 18, 1327-1332.
64. Yuan, R.H., Jeng, Y.M., Chen, H.L., Lai, P.L., Pan, H.W., Hsieh, F.J., Lin, C.Y., Lee, P.H., and Hsu, H.C. (2006). Stathmin overexpression cooperates with p53 mutation and osteopontin overexpression, and is associated with tumour progression, early recurrence, and poor prognosis in hepatocellular carcinoma. J Pathol 209, 549-558. (Pubitemid 44194570)
65. Zeng, Y., Cai, X., and Cullen, B.R. (2005). Use of RNA poly-merase II to transcribe artificial microRNAs. Methods En-zymol 392, 371-380. (Pubitemid 40092526)
66. Zhang, H.Z., Gao, P., Yan, L., and Lin, F. (2004). Significance of stathmin gene overexpression in osteosarcoma cells. Ai Zheng 23, 493-496.
67. Zhang, H.Z., Wang, Y., Gao, P., Lin, F., Liu, L., Yu, B., Ren, J.H., Zhao, H., and Wang, R. (2006). Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells. Cancer Biol Ther 5, 14571461.
68. Zhang, S., Zhao, B., Jiang, H., Wang, B., and Ma, B. (2007). Ca-tionic lipids and polymers mediated vectors for delivery of siRNA. J Control Release 123, 1-10. (Pubitemid 47444388)