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Gene therapy, anti-cancer, cell targeting, apoptosis.

Mohd. Azmi Mohd. Lila, and Shia, John Kwong Siew and Hayati Zakaria, and Suria Mohd. Saad, and Lim, Sen Ni and Jafri Malin Abdullah, (2004) Gene therapy, anti-cancer, cell targeting, apoptosis. Malaysian Journal of Medical Sciences, 11 (1). pp. 9-23. ISSN 1394195X

Full text not available from this repository.

Official URL: http://www.medic.usm.my/publication/mjms/

Affiliations

Universiti Putra Malaysia, Institute of Bioscience
Universiti Sains Malaysia, School of Medical Sciences, Dept. of Neurosciences

Abstract

Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene therapy research and its application in relation to anti-cancer treatment.

Item Type:Journal
Keywords:Gene therapy, anti-cancer, cell targeting, apoptosis, Biotechnology
Subjects:Q Science
R Medicine
ID Code:619

Roland, A.P., From genes to gene medicines: Recent advances in nonviral gene delivery. Crit. Rev. Ther. Drug Carrier Syst. 1998; 15: 143-198

Magari, S. R., Rivera, V. M., luliucci, J. D., Gilman, M., and Cerasoli, F., Pharmacologic control of a humanized gene therapy system implanted into nude mice. J. Clin. Invest. 1997; 100: 2865-2872.

Mahato, R.I., Takakura, Y., and Hashida, M., Development of targeted delivery systems for nuclei acid drugs. J. Drug Target. 1997; 4:337-357 4).

Lee, .R.J., and Huang, L., Lipidic vector system s for gene transfer. Crit. Rev. Ther. Drug Carrier syst. 1997;14: 173-206.

Meyer, K.E.B., Uyechi, L.S., and Szoka, E.c.,Manipulating the intracellular trafficking of nucleic acids. In: Gene therapy For Diseases of the Lung (K.L.brigham, ed.), pp135-180. Dekker, New York 1997.

Worgall, S., Wolff, G., falck-Pedersen, E., and Crystal, R.G., Innate immune mechanisms cominate elimination of adeniviral vectors following in vivo administration. Hum. Gen. Ther. 1997; 8: 37-44.

Cichon, G., and Strauss, M., Transient immunosuppression with 15-deoxyspergualin prolongs reporter gene expression and reduces humoral immune response after adenoviral gene transfer. Gene Ther. 1998; 5:85-90.

Zhao, D.D, Watarai, S.S., Lee, J.T., Kouchi, S., Ohmori, H., and and Yusuda, T., Gene transfection by cationic liposomes: Comparison of the transfection efficiency of liposomes prepared prepared from various positively charged lipids. Acta Med Okayama 1997 ; 51: 149-154

Li, S., Tseng, W.C., Beer Stolz, D., Wu, S.P., Watkins, S.C., and Huang. L., Dynamic changes in the characteristics of cationic lipidic vectors after exposure to mouse serum: Implications for intravenous lipofection. Gene Ther. 1999; 6: 585-594.

Li, S.,Rizzo, M.A., Bhattacharya, S., and Huang, L., Characterization of cationic lipid-protamine-DNA (LPD) complexes for intravenous gene delivery. Gene Ther. 1998; 5: 930-937

Barron, L.G., Meyer, K.B., and Szoka, F.C., Jr., Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes. Hum. Gene. Ther. 1998; 2: 151-155

Rother, R.P., Fodor, W.L., Springhorn, J.P., Birks, C.W., Setter, E., Sandrin, M.S., Suquinto, Sp.P., and Rollins, S.A., A novel mechanism of retrovirus inactivation in

human serum mediated by anti-alpha-galactosyl natural antibody. J. Exp. Med. 1995; 182: 1345-1355

Pensierro, M.N. Wysocki, C.A., Nader, K., and Kikuchi, G.E., Development of amphotropic murine retrovirus vectors resistant to inactivation by human serum. Hum. Gene Ther. 1996; 7: 1095-1101

Mahato, R.I., Anwer, K., Tagliaferri, F., Meaney, C., Leonard, P., Wad, M.S., Logan, M., Frech, M., and Rolland, A., Biodistribution and gene expression of lipid/ plasmid complexes after systemic administration. Hum Gene. Ther. 1998; 9: 2083-2099

Niven, R., Pearlman, R., Wedeking, T., Mackeigan, J., Noker, P., Simpson-Herren, L., and Smith, J.G., Biodistribution of radio-labeled lipid-DNA complexes and DNA in mice. J. Pharm. Sci. 1998; 87: 1292-1299.

Grisenbach, U., Chonn,A., Cassady, R., Hannam, V., Ackerley, C., Post, M., Tanswell, A.K., Olek, K., O’Brodvich, H., and Tsui, L.C. Comparison between intratracheal and intravenous administration of liposome-DNA complexes for cystic fibrosis lung gene

therapy. Gene Ther. 1998; 5:181-188

McDonald, R.J., Liggitt, H.D., Roche, L., Nguyen, H.T., Pearlman, R., Raabe, O.G., Bussey, L.B., and Gorman, C.M., Aerosol delivery of lipid: DNA complexes to lungs of rhesus monkeys. Pharm. Res. 1998; 15: 671-679

Kitson, C., Angel, B., Judd, D., Rothery, S., Severs, N.J., Dewar, A., Huang, L., Wadsworth, S.C., Cheng, S.H., Geddess, D.M., and Alton, E.W.E.W., The extra and

intracellular barriers to lipid and adenovirusmediated pulmonary gene transfer in native sheep airway epithelium. Gene Ther. 1999; 6: 534-546

Stern, M., Caplen, N.J., Browning, J.E., Grisenbach, U., Sorgi, E., Huang, L., Gruenert, D.C., Marriot, C., Crystal, R.G., Geddes, D.M., and Alton, E., The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro. Gene Ther. 1999; 5: 91-98

Noruma, T., Yasuda, K., Yamada, T., Okamoto, S., Mahato, R.I., Wataneba, Y., Takakura, Y., and Hashida, M., Gene expression and antitumor effects following direct interferon (IFN)-gamma gene transfer with naked plasmid DNA and DC-chol liposome complexes in mice. Gene Ther. 1999; 6: 121-129

Kessler, P.D., Podsakoff, G.M., Chen, X., McQuiston, S.A., Colosi, P.C, Matelis, L.A., Kurtzman, G.J.and Byrne, B.J., Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein. Proc. Natl. Acad. Sci. U.S.A. 1996; 93: 14082-14087.

Marshall, D.J., and Leide, J.M. Recent advances in skeletal-muscle-based gene therapy. Curr. Opin, Genet. Dev. 1998; 8: 360-365 :19

Monahan, P.E., Samulski, R.J., Tazelaar, J., Xiao, X., Nichols, T.C., Bellinger, D.A., read, M.S., and walsh, C.E., Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dogmodel of hemophila. Gene Ther. 1998; 5: 40-49

Mahvi, D.M., Sheehy, M.J., and Yang, N.S., DNA cancer vaccines: A gene gun approach. Immunol. Cell Biol. 1997; 75: 456-460.

Rakhmilevich, A.l., Timmins, J.G., Janssen, K., Poohmann, E.L., Sheehy, M.J., and Yang, N.S. Gene gun-mediated IL-12 gene therapy induces antitumor effects in the absence of toxicity: A direct comparison with systemic IL-12 protein therapy. J. Immunother.1999; 22: 135-144

Mir, L.M., Bureau, M.E., Gelh, J., Rangra, R., Rouy, D., Caullaud, J.M., Delaere, P., Branellec, D.,Schwartz, B., and Scherman, D., High efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc. Natl. Acad. Sci, U.S.A. 1999; 96: 4262-4267

Li, Y., Pong, R.V., Bergelson, J.M., Hall, M.C., Sagolowsky, A.I., Tsaeng, C.P., Wang, Z., and Hsieh, J.T., Loss of adenoviral receptor expression in human bladder cancer cells: A potential impact on the efficacy of gene therapy. Cancer Res. 1999; 59: 325-330

Nalbantoglu, J., Pari, G., Karpati, G., and Holland, P.C., Expression of the primary coxsakie and adenovirus receptor is downregulated during skeletal muscle maturation and limits the efficacy of adenovirusmediated gene delivery to muscle cells. Hum. Gene Ther. 1999; 10: 1009-1019

Hemmi S, Geertsen R, Mezzacasa A, Peter I, Dummer R. The presence of human coxsackievirus and adenovirus receptor is associated with efficient adenovirus-mediated transgene expression in humanmelanoma cell cultures Hum. Gene Ther 1998; 9: 2363-73.

Hidaka, C., Milano, E., Leopold, P.L., Bergelson, J.M., Hackett, N.R., Finberg, R.W., Wickham, T.J., Kovesdi, I., Roelvink, P., and Crystal, R.G., CAR-cependent and CAR-independent pathways of adenovirus vector mediated gene transfer and expression in human fibroblasts. J. Clin. Invest. 1999; 103: 579-587

Bilbao, G., Gomez-Navarro, J., and Curiel, D.T., Targeted adenoviral vectors for cancer gene therapy. Adv. Exp. Med. Biol. 1998; 451: 365-374

Bartlett, J.S., Kleinschmidt, J., Boucher, R.C., and Samulski, R.J., Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by bispecific F(Ab)2, antibody. Nat Biotechnol. 1999;17:181-186.

Rogers, B.E., Douglas, J.T., Ahlem, C., Buchsbaum, D.J., Frincke, J., and Curiel, D.T., Use of a novel crosslinking method to modify adenovirus tropism. Gene Ther. 1997; 4: 1387-1392.

Rancourt, C., Rogers, B.E.,Sosnowski, B.A., Wang, M., Pichem A., Pierce, G.F., Alvarez, R.D., Siegal, G.P., Douglas, J.T., and Curiel, D.T., Basic Fibroblast growth

factor enhancement of adenovirus-mediated delivery of the herpes simplex virus thymidine kinase gene results in augmented therapeutic benefit in a murine model of ovarian cancer. Clin. Cancer. Res. 1998; 4:2455-2461.

Miller, D.G., Adam, M.A., and Miler, A.D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol.Cell. Biol. 1990; 10: 4230-4242.

Orlic D, Girard L.J, Jordan C.T, Anderson S.M, Cline A.P, Bodine DM. The level of MRNA encoding the amphotropic retrovirus receptor in mouse and human hematopoietic stem cells is low and correlates with the efficiency of rotavirus transduction Proc Natl Acad Sci. 1996; 93: 11097-102.

Kurre, P, Kiem, H.R, Morris, J., Heyward, S., Battini, J.L., and Miller, A.D., Efficient transduction by an amphotropic retrovirus vector is dependent on high level expression of the cell surface virus receptor. J.Virol. 1999; 73: 495-500.

Palsson, B., and Andreadis, S., The physico-chemical factors that govern retrovirus-mediated gene transfer. Exp. Hematol. 1997; 25: 94-102.

Hope, M.J., Mui, B., Ansell, S., and Ahkong, Q.F., Cationic lipids, phosphatidylethanolamine and the intracellular delivery of polymeric, nucleic acid-based

drugs. Mol. Membr. Biol. 1998; 15: 1-14.

Cristiano, R.J., Targeted, non-viral gene delivery for cancer gene therapy. Front. Biosci. 1998; 3:Dl 161-D1170.

Morsy, M.A., and Caskey, C.T., Expanded-capacity adenoviral vectors—The helper-dependent vectors.Mol. Med Today 1999; 5: 18-24.

Wagner, E., Effects of membrane-active agents in gene delivery. J. Controlled Release 1998; 53:155 -158

Zabner, J., Fasbender, A.J., Moninger, E, Poellinger, K.A., and Welsh, M.J., Cellular and molecular barriersto gene transfer by a cationic lipid. J. Biol. Chem. 1995; 270:18997-19007.

Brisson, M., He, Y., Li, S., Yang, J.P., and Huang, L., A novel T7 RNA polymerase autogene for efficient cytoplasmic expression of target genes. Gene Ther.1999; 6:263—270.

Baru, M., Nahum, O., Jaaro, H., Sha’anani, J., and Nur, I. Lysosome-disrupting peptide increases the efficiency of in-vivo gene transfer by liposome-encapsulated DNA. J. Drug Target. 1998; 6: 191-199.

Fasbender, A., Zabner, J., Zeiher, B.G., and Welsh, M. J., A low rate of cell proliferation and reduced DNA uptake limit cationic lipid-mediated gene transfer to primary cultures of ciliated human airway epithelia. Gene Ther. 1997; 4: 1173-1180.

Greber.U. R, and Kasamatsu, H., Nuclear targeting of SV40 and adenovirus. Trends Cell Biol. 1996; 6: 89-195.

Ludtke, J. J., Zhang, G., Sebestyen, M.G., and Wolff, J.A., A nuclear localization signal can enhance both the nuclear transport and expression of 1 kbDNA. J. Cell Sci. 1999; 112: 2033-2041

Zanta, M.A., Belguise-Valladier, P., and Behr, J.P.,Gene delivery: A single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus.Proc. Natl. Acad. Sci. U.S.A. 1999; 96:91-96.

Dean, D.A. Import of plasmic DNA into the nucleus is sequence specific. Exp. Cell Res. 1997; 230: 293-302.

Graessmann, M., Menne, J., Liebler, M., Graeber, I.,and Graessmann, A., Helper activity for gene expression, a novel function of the SV40 enhancer. Nucleic Acids Res. 1989; 17: 6603-6612.

Chen, X., Li, Y., Xiong, K., Aizicovici, S., Xie, Y, Zhu, Q., Sturtz, E, Shulok, J.,Snodgrass, R., Wagner, T.E., and Plan-ka, D., Cancer gene therapy by direct tumor injections of a nonviral T7 vector encoding a thymidine kinase gene. Hum. Gene Ther. 1998; 9: 729-736.

Lechardeur, D., Sohn, K.Haardt, M., Joshi, P.B., Monck, M., Graham, R.W., Beatty, B., Squire, J., O’Brodovich,H., j and Lukacs, G.L., Metabolic instability of plasmid DNA in the cytosol: A potential barrier to gene transfer. J. Gene Ther. 1999; 6:482-497.

Luby-Phelps, K., Physical properties of cytoplasm. Curr. Opin. Cell Biol. 1994; 6: 3-9.

Suomalainen, M., Nakano, M. Y., Keller, S., Boucke, K., Stidwill, R.P., and Greber, U.E., Microtubuledependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J. CellBiol. 1999; 144: 657-672.

Tripathy, S.K., Black, H.B., Goldwasser, E., and Leiden, M., Immune responses to transgeneencodedproteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat. Med. 1996; 2:545-550.

Yang, Y., Nunes, F.A., Berencsi, K., Gonczol, E., Engelhardt, J.E, and Wilson, J.M., Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosis. Nat. Genet.1994; 7: 362-369.

Yang, Y., Jooss, K.U., Su, Q., Ertl, H.C., and Wilson, J.M., Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. Gene Ther. 1996; 3: 137-144.

Yang, Y., Greenough, K., and Wilson, J.M., Transient immune blockade prevents formation of neutralizing antibody to recombinant adenovirus and allows repeated gene transfer to mouse liver. Gene Ther. 1996;

Bouvet, M., Fang, B., Ekmekcioglu, S., Ji,L., Bucana, C.D., Hamada, K., Grimm, E.A., and Roth, J.A., Suppression of the immune response to an adenovirus vector and enhancement of intratumoral transgene expression by low-dose etoposide. Gene Ther. 1998; 5: 189-195.

Elshami, A.A., Kucharczuk, J.C, Sterman, D.H.,Smythe, W.R., Hwang, H.C, Amin, K.M., Lir/ky, L.A., Albelda, S.M., and Kaiser, L.R., The role of immunosuppression in the efficacy of cancer genetherapy using adenovirus transfer of the herpes simplex thymidine kinase gene. Ann. Surg. 1995; 222:298-307,

Barr, D., Tubb, J., Ferguson, D., Scaria, A., Lieber, A., Wilson, C., Perkins, J., and Kay, M.A., Strain related variations in adenovirally mediated transgene expression from mouse hepatocytes in vivo: Comparisons between im-munocompetent and immunodeficient inbred strains. Gene Ther. 1995; 2: 151-155.

Zsengeller Z.K, Wert S.E, Hull W.M, Hu X, Yei S, Trapnell B.C, Whitsett J.A. Persistence ofreplication deficient adenovirus-mediated gene transfer in lung of immune-deficient (nu/nu) mice. Hum Gene Ther, 1995; 6:457-67

Morsy, M.A., Gu, M.C., Zhao, J.Z., Holder, D.J., Rogers, I.T, Pouch, W.J., Motzel, S.L., Klein, H.J.,Gupta, S.K., Liang, X., Tota, M.R., Rosenblum, C.I., and Caskey, C.T., Leptin gene therapy and daily protein administration: A comparative study in the ob/ob mouse. Gene Ther. 1998; 5: 8 -18.

Carter, B.J. Adeno-associated virus and AAV vectors for gene delivery. In “Gene Therapy: Therapeutic Mechanisms and Strategies” (D. Lasic and N.Templeton-Smith, eds.). Dekker, New York (in press)(2000).

Hallek, M., and Wendtner, C.M., Recombinant adenoassociated virus (rAAV) vectors for somatic gene therapy: Recent advances and potential clinical applications. Cytokines Mol. Ther. 1996; 2:69-79.

Rabinowitz, J.E., and Samulski, J.,Adeno-associated virus expression systems for gene transfer. Curr. Of in. Biotechnol. 1998; 9: 470-475.

Snyder, R.O., Spratt, S.K., Lagarde, C., Bohl, D., Kaspar, B., Sloan, B., Cohen, L.K., and Danos, O., Efficient and stable adeno-associated virus-mediated transduction in the skeletal muscle of adult immunocompetent mice. Hum. Gene Ther. 199; 8:1891-1900.

Miller, N., and Whelan, J. Progress in transcriptionally targeted and regulatable vectors for genetic therapy. Hum.GeneTher. 1997 8: 803-8l5.

Walther, W., and Stein, U. Cell type specific and inducible promoters for vectors in gene therapy as an approach for cell targeting. J. Mol. Med. 1996; 74: 379-392.

Wolff, J.A., Ludtke, J.J., Acsadi, G., William, P., and Jani, A., Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1992; 1: 363-369.

Guanghuan., T, Korchmaiet, A.L., Liggitt, H.D., Yu, W.H., Heath, T.D., and Debs, R.J., Non-replicating EBV-based plasmids produce long-term gene expression in vivo. Submitted for publication 1999.

Springer, M.L., Chen, A.S., Kraft, P.E., Bednarski, M., and Blau, H.M., VEGF gene delivery to muscle: Potential role for vasculogenesis in adults. Mol. Cell 1998; 2: 549-558.

Sclimenti, C.R., and Calos, M.P., Epstein-Barr virus vectors for gene expression and transfer. Curr. Opin. Biotechnol. 1998; 9: 476-479.

Piirsoo, M., Ustav, E., Mandel, T, Stenlund, A., and Ustav, M., Cis and trans requirements for stable episomal maintenance of the BPV-1 replicator. EMBOJ. 1996; 15: 1-11.

Calos, M.P., Stability without a centromere. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 4084-4085.

Rickinson, A.B.,and Kieff, E. Epstein-Barr virus. In “Fields Virology” (B. N. Fields, D. M. Knipe, and P. M. How-ley, eds.), pp. 2397-2446. Lippincott-Raven, Philadelphia 1996.

Wilson, J.B., Bell, J.L., and Levine, A.J., Expression of Epstein-Barr virus nuclear antigen-1 induces B cell neoplasia in transgenic mice. EMBOJ. 1996; 15: 3117-3126.

Cooper, M.J., Lippa, M., Payne, J.M., Hatzivassiliou, G., Reifenberg, E., Fayazi, B., Perales, J.C., Morrison, L.J.,Tem pleton, D., Piekarz, R.L., and Tan, J., Safetymodified episomal vectors for human gene therapy. Proc. Ntd Acad. Sci. U.S.A. 1997; 94:6450-455.

Clackson, T., Controlling mammalian gene expression with small molecules. Curr. Opin. Ghem. Biol. 1997; 1: 210-218

No, D., Yao, T.P., and Evans, R.M., Ecdysoneinducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Set. U.S.A. 1996; 93: 3346-3351.

Blau, H.M., and Rossi, E M., Tet B or not tet B: Advances in tetracydine-inducible gene expression. Proc. NaL Acad. Sd. U.S.A. 1999; 96: 797-799,

Rivera, V.M., Clackson, T, Natesan, S., Pollock, R., Amara, J.E, Keenan, T, Magari, S. R., Phillips, T, Courage, N.L., Cerasoli, E, Jr., Holt, D. A., and Gilman, M., A humanized system for pharmacologic control of gene expression. Nat. Med. 1996; 2: 1028-1032.

Ye, X., Rivera, V.M., Zoltick, P., Cerasoli, E, Jr.,

Schnell, M. A., Gao, G., Hughes, J. V, Gilman, M., and Wilson, J. M., Regulated delivery of therapeutic proteins after in vivo somatic cell gene transfer. Science 1999; 283: 88-91.

Burcin, M.M., Schiedner, G., Kochanek, S.,Tsai, S.Y, and O’Malley, B.W., Adenovirus-mediated regulable target gene expression in vivo. Proc. Natl.Acad. Sci. U.S.A. 1999; 96: 355-360

Benihoud, K., Saggio, I., Opolon, P., Salone, B., Amiot, E, Connault, E., Chianale, C., Dautry, E, Yeh, P., and Perricaudet, M., Efficient, repeated adenovirusmediated gene transfer in mice lacking both tumor necrosis factor alpha and lymphotoxin alpha. J. Virol.1998; 72: 9514-9525.

Dong, J.Y., Wang, D., Van Ginkel, F.W., Pascual, D.W, and Frizzell, R.A., Systematic analysis of repeated gene delivery into animal lungs with a recombinant adenovirus vector. Hum. Gene Ther. 1996; 7: 319-331

Kagami, H., Atkinson, J.C., Michalek, S.M., Handelman, B., Yu, S., Baum, B.J., and O’Connell, B., Repetitive adenovirus administration to the parotid gland: Role of immunological barriers and inductionof oral tolerance. Hum. Gene. Ther. 1998; 9: 305-313.

Smith L.M, Birrer M.J. Use of transcription factors as agents and targets for drug development oncology (Hunlight) 1996; 10: 1532-8.

Yei, S., Mittereder, N.,Tang, K., O’Sullivan, C., and Trapnell, B.C., Adenovirus-mediated gene transfer for cystic fibrosis: Quantitative evaluation of repeated in

vivo vector administration to the lung. Gene Ther.1994; 1: 192-200.

Kafri, T, Morgan, D., Krahl, T, Sarvetnick, N., Sherman, L., and Verma, I., Cellular immune response to adenoviral vector infected cells does not require de novo viral gene expression: Implications for gene therapy. Proc. Natl Acad. Sci. U.S.A. 1998; 95: 11377-11382.

Kass-Eisler, A., Leinwand, L., Gall, J., Bloom, B., and Falck-Pedersen, E., Circumventing the immune response to I adenovirus-mediated gene therapy. Gene

Ther. 1996; 3: 154- 162.

Roy, S., Shirley, P.S., McClelland, A., and Kaleko, M., Circumvention of immunity to the adenovirus major coat protein hexon. J. Virol. 1998; 72: 6875-6879

Rutledge, E.A., Halbert, C.L., and Russell,D.W.,Infectious clones and vectors derived from adenoassociated virus (AAV) serotypes other than AAV type 2. J. Virol. 1998; 72: 309-319.

Xiao, W., Chirmule, N., Berta, S.C., McCullough, B., Gao, G., and Wilson, J M., Gene therapy vectors based on adeno-associated virus type I. J. Virol. 1999; 73:3994-4003..

Song, Y.K., Liu, E, Chu, S., and Liu, D., Characterization of cationic liposome-mediated gene transfer in vivo intravenous administration. Hum. Gene Ther. 1997; 8: 1585-1594.

Dow, S.W, Fradkin, L.G., Liggitt, H.D., Willson, A.E, Heath, T.D., and Potter, T.A., Lipid-DNA complexes induce potent activation of innate immune responses and and tumor activity when administered intravenously. J. Immunol. 1999; 163: 1552-1561.

Whitmore, M., Li, S., and Huang, L., LPD lipopolyplex initiates a potent cytokine response and inhibits tumor growth. Gene Therap. 1999; 6: 1867-1875

Winston W.M.; Molodowitch C.; Hunter C.P. Systemic RNAi in C. elegans requires the putatice transmembrane protein SID-1. Science 2002; 295: 2456-2459.

Zamore, P.D., Tuschl, T., Sharp, P.A., Bartel, D.P., RNAi: Double-stranded RNA directs the ATPdependent cleavage of mRNA at 21 to 23 nuvleotide intervals. Cell 2000; 101: 25-33.

Krieg, A.M., An innate immune defense mechanism based on the recognition of CpG motifs in miciobial DNA. J. Lab. Clin. Med. 1996; 128: 128-133.

Pisetsky, D.S., Immune activation by bacterial DNA: A new genetic code. Immunity 1996; 5: 303-310.

Hutvagner, G. and Zamore,P.D., RNAi: Nature abhors a bouble-strand. Curr. Opin. Genet. Dev. 2002; 12:225-232.

Elbashir, S.M., Lendeckel, W., Tuschl, T., RNA interference is mediated by 21- and 22- nucleotide RNAs. Genes Dev. 2001; 15: 188-200.

Ahlquist, P., RNA-dependent RNA polymerases, viruses, and RNA silencing. Science 2000; 296: 1270- 1273.

Lewis, D.L., Specific inhibition of gene expression in post-natal mammals using small interfering RNAs. Keystone symposia: RNA interference, cosuppression and related Phenomena, 2002, February 21-26.Abstract no. 312..

Pachuk, C.J., dsRNA mediated post-transcriptional gene silencing and the interferon response in human cells and an adult mouse model. Keystone symposia: RNA interference, co-suppression and related Phenomena, 2002, February 21-26. Abstact: 217

Caplen N.J.; Parrish S.; Imani F.; Fire A.; Morgan R.A., Specific inhibition of gene expression by small doublestranded RNAs in invertebrate and vertebrate system. Proc. Natl. Acad. Sci. U.S.A. 2001; 98: 9742-9747

Parrish, S., and Fire., A distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. 2001; RNA 4: 1397-1402.

Yu, J.Y., DeRuiter, S.L., Turner, D.L., RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 6047-6052

Holen, T., Amarzguioui, M., Wiiger, M.T., Babaie, E., Prydz, H., Positional effects of short interfering RNAs targeting the human coagulation trigger tissue factor. Nuclei Acids Res. 2002; 30: 1757-1766.

Brummelkamp, T.R., Bernards. R., Agami, R., A system for stable expression of short interfering RNAs in mammalian cells. Science 2002; 296: 550-553.

Mohd Azmi Mohd Lila, John Shia Kwong Siew et. Al 110) Myslinski E.; Amé J.C.; Krol A.; Carbon P. An unusually compact external promoter for RNA polymerase III transcription of the human H1RNA gene. Nucleic Acids Res. 2001; 29: 2502-2509

Paddison, P.J; Caudy, A.A; Hannon, G.J. Stable expression of gene expression by RNAi in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 1443-1448.

Miyagishi, M., and Tiara, K. U6 promoter-driven siRNAs with four uridine 3’ overhangs efficiently suppress targeted gene expression in mammalian cells.Nat. Biotechnol. 2002; 19: 497-500

Lee N.S.; Dohjima T.; Bauer G.; Li H.; Li M.J.; Ehsani A.; Salvaterra P.; Rossi J. Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat. Biotechnol. 2002; 19: 500-505.

Paddison, P.J; Caudy, A.A; Bernstein, E; Hannon, G.J; Conklin, D.S. Short hairpin RNAs induce sequence specific silencing in mammalian cells. Genes. Dev.,

2002; 16: 948-958.

Pachuk, C.J., Ciccarelli, R.B., Samuel, M., Bayer, M.E., TroutmanJr,R.D., Zurawski, D.V. Schauer, J.I., Higgins, T.J., Weiner, D.B., Sosnoski, D.M., ZurawskiJr., V.R. and C. Satishchandran. Characterisation of a new class of DNA delivery complexes fromed by the local anesthetic bupivican. Biochim. Biophys. Acta 2001; 1468: 20-30.

Noteborn, M.H.M., Van der Eb, A.J., Koch, G. and Jeurissen, S.H.M. VP3 of the chicken anemia virus (CAV) causes apoptosis. In Vaccines ed. H.S. Ginsberg., F. Brown., R.M. Chanock, and R.A. Lerner, pp299-304. Cold Spring Harbor, New Yo