Development Of A Liver-specific Tet-on Inducible System For Aav Vectors And Its Application In The Treatment Of Liver Cancer

dc.creatorVanrell L.
dc.creatorDi Scala M.
dc.creatorBlanco L.
dc.creatorOtano I.
dc.creatorGil-Farina I.
dc.creatorBaldim V.
dc.creatorPaneda A.
dc.creatorBerraondo P.
dc.creatorBeattie S.G.
dc.creatorChtarto A.
dc.creatorTenenbaum L.
dc.creatorPrieto J.
dc.creatorGonzalez-Aseguinolaza G.
dc.date2011
dc.date2015-06-30T20:18:19Z
dc.date2015-11-26T14:47:57Z
dc.date2015-06-30T20:18:19Z
dc.date2015-11-26T14:47:57Z
dc.date.accessioned2018-03-28T21:58:37Z
dc.date.available2018-03-28T21:58:37Z
dc.identifier
dc.identifierMolecular Therapy. , v. 19, n. 7, p. 1245 - 1253, 2011.
dc.identifier15250016
dc.identifier10.1038/mt.2011.37
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79959972143&partnerID=40&md5=8299069363ec282cf64b78a94c6490d8
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/107511
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/107511
dc.identifier2-s2.0-79959972143
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1253468
dc.descriptionRecombinant adeno-associated virus (rAAV) are effective gene delivery vehicles that can mediate long-lasting transgene expression. However, tight regulation and tissue-specific transgene expression is required for certain therapeutic applications. For regulatable expression from the liver we designed a hepatospecific bidirectional and autoregulatory tetracycline (Tet)-On system (Tet bidirAlb) flanked by AAV inverted terminal repeats (ITRs). We characterized the inducible hepatospecific system in comparison with an inducible ubiquitous expression system (Tet bidirCMV) using luciferase (luc). Although the ubiquitous system led to luc expression throughout the mouse, luc expression derived from the hepatospecific system was restricted to the liver. Interestingly, the induction rate of the Tet bidir Alb was significantly higher than that of Tet bidirCMV, whereas leakage of Tet bidir Alb was significantly lower. To evaluate the therapeutic potential of this vector, an AAV-Tet bidir-Alb-expressing interleukin-12 (IL-12) was tested in a murine model for hepatic colorectal metastasis. The vector induced dose-dependent levels of IL-12 and interferon-γ (IFN-γ), showing no significant toxicity. AAV-Tet bidir-Alb-IL-12 was highly efficient in preventing establishment of metastasis in the liver and induced an efficient T-cell memory response to tumor cells. Thus, we have demonstrated persistent, and inducible in vivo expression of a gene from a liver-specific Tet-On inducible construct delivered via an AAV vector and proved to be an efficient tool for treating liver cancer. © The American Society of Gene & Cell Therapy.
dc.description19
dc.description7
dc.description1245
dc.description1253
dc.descriptionGrieger, J.C., Samulski, R.J., Adeno-associated virus as a gene therapy vector: Vector development, production and clinical applications (2005) Advances in Biochemical Engineering/Biotechnology, 99, pp. 119-145. , DOI 10.1007/10-005, Gene Therapy and Gene Delivery Systems
dc.descriptionDaya, S., Berns, K.I., Gene therapy using adeno-associated virus vectors (2008) Clin Microbiol Rev, 21, pp. 583-593
dc.descriptionGossen, M., Bujard, H., Tight control of gene expression in mammalian cells by tetracycline-responsive promoters (1992) Proc Natl Acad Sci USA, 89, pp. 5547-5551
dc.descriptionStieger, K., Belbellaa, B., Le Guiner, C., Moullier, P., Rolling, F., In vivo gene regulation using tetracycline-regulatable systems (2009) Adv Drug Deliv Rev, 61, pp. 527-541
dc.descriptionWu, Z., Yang, H., Colosi, P., Effect of genome size on AAV vector packaging (2010) Mol Ther, 18, pp. 80-86
dc.descriptionChtarto, A., Bender, H.U., Hanemann, C.O., Kemp, T., Lehtonen, E., Levivier, M., Brotchi, J., Tenenbaum, L., Tetracycline-inducible transgene expression mediated by a single AAV vector (2003) Gene Therapy, 10 (1), pp. 84-94. , DOI 10.1038/sj.gt.3301838
dc.descriptionChtarto, A., Yang, X., Bockstael, O., Melas, C., Blum, D., Lehtonen, E., Abeloos, L., Tenenbaum, L., Controlled delivery of glial cell line-derived neurotrophic factor by a single tetracycline-inducible AAV vector (2007) Experimental Neurology, 204 (1), pp. 387-399. , DOI 10.1016/j.expneurol.2006.11.014, PII S0014488606006303
dc.descriptionKramer, M.G., Barajas, M., Razquin, N., Berraondo, P., Rodrigo, M., Wu, C., Qian, C., Prieto, J., In vitro and in vivo comparative study of chimeric liver-specific promoters (2003) Molecular Therapy, 7 (3), pp. 375-385. , DOI 10.1016/S1525-0016(02)00060-6
dc.descriptionZabala, M., Wang, L., Hernandez-Alcoceba, R., Hillen, W., Qian, C., Prieto, J., Kramer, M.G., Optimization of the Tet-on system to regulate interleukin 12 expression in the liver for the treatment of hepatic tumors (2004) Cancer Research, 64 (8), pp. 2799-2804. , DOI 10.1158/0008-5472.CAN-03-3061
dc.descriptionPañeda, A., Vanrell, L., Mauleon, I., Crettaz, J.S., Berraondo, P., Timmermans, E.J., Effect of adeno-associated virus serotype and genomic structure on liver transduction and biodistribution in mice of both genders (2009) Hum Gene Ther, 20, pp. 908-917
dc.descriptionTrinchieri, G., Interleukin-12 and the regulation of innate resistance and adaptive immunity (2003) Nature Reviews Immunology, 3 (2), pp. 133-146. , DOI 10.1038/nri1001
dc.descriptionRakhit, A., Yeon, M.M., Ferrante, J., Fettner, S., Nadeau, R., Motzer, R., Bukowski, R., Gately, M.K., Down-regulation of the pharmacokinetic-pharmacodynamic response to interleukin-12 during long-term administration to patients with renal cell carcinoma and evaluation of the mechanism of this 'adaptive response' in mice (1999) Clinical Pharmacology and Therapeutics, 65 (6), pp. 615-629. , DOI 10.1016/S0009-9236(99)90083-8
dc.descriptionLeonard, J.P., Sherman, M.L., Fisher, G.L., Buchanan, L.J., Larsen, G., Atkins, M.B., Sosman, J.A., Ryan, J.L., Effects of single-dose interleukin-12 exposure on interleukin-12 associated toxicity and interferon-γ production (1997) Blood, 90 (7), pp. 2541-2548
dc.descriptionBarajas, M., Mazzolini, G., Genovie, G., Bilbao, R., Narvaiza, I., Schmitz, V., Sangro, B., Prieto, J., Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12 (2001) Hepatology, 33 (1), pp. 52-61. , DOI 10.1053/jhep.2001.20796
dc.descriptionLui, V.W.Y., Falo Jr., L.D., Huang, L., Systemic production of IL-12 by naked DNA mediated gene transfer: Toxicity and attenuation of transgene expression in vivo (2001) Journal of Gene Medicine, 3 (4), pp. 384-393. , DOI 10.1002/jgm.201
dc.descriptionSangro, B., Mazzolini, G., Ruiz, J., Herraiz, M., Quiroga, J., Herrero, I., Benito, A., Prieto, J., Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors (2004) Journal of Clinical Oncology, 22 (8), pp. 1389-1397. , DOI 10.1200/JCO.2004.04.059
dc.descriptionWang, L., Hernandez-Alcoceba, R., Shankar, V., Zabala, M., Kochanek, S., Sangro, B., Kramer, M.G., Qian, C., Prolonged and inducible transgene expression in the liver using gutless adenovirus: A potential therapy for liver cancer (2004) Gastroenterology, 126 (1 SUPPL. 1), pp. 278-289. , DOI 10.1053/j.gastro.2003.10.075
dc.descriptionLieschke, G.J., Rao, P.K., Gately, M.K., Mulligan, R.C., Bioactive murine and human interleukin-12 fusion proteins which retain antitumor activity in vivo (1997) Nat Biotechnol, 15, pp. 35-40
dc.descriptionReboredo, M., Zabala, M., Mauleon, I., De Las Rivas, J., Kreppel, F., Kochanek, S., Prieto, J., Kramer, M.G., Interleukin-12 inhibits liver-specific drug-inducible systems in vivo (2008) Gene Therapy, 15 (4), pp. 277-288. , DOI 10.1038/sj.gt.3303073, PII 3303073
dc.descriptionZabala, M., Alzuguren, P., Benavides, C., Crettaz, J., Gonzalez-Aseguinolaza, G., Ortiz De Solorzano, C., Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy (2009) Mol Cancer, 8, p. 2
dc.descriptionCrettaz, J., Berraondo, P., Mauleon, I., Ochoa, L., Shankar, V., Barajas, M., Van Rooijen, N., Gonzalez-Aseguinolaza, G., Intrahepatic injection of adenovirus reduces inflammation and increases gene transfer and therapeutic effect in mice (2006) Hepatology, 44 (3), pp. 623-632. , DOI 10.1002/hep.21292
dc.descriptionAllocca, M., Doria, M., Petrillo, M., Colella, P., Garcia-Hoyos, M., Gibbs, D., Kim, S.R., Auricchio, A., Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice (2008) Journal of Clinical Investigation, 118 (5), pp. 1955-1964. , http://www.jci.org/articles/view/34316/pdf, DOI 10.1172/JCI34316
dc.descriptionMcGee Sanftner, L.H., Rendahl, K.G., Quiroz, D., Coyne, M., Ladner, M., Manning, W.C., Flannery, J.G., Recombinant AAV-mediated delivery of a tet-inducible reporter gene to the rat retina (2001) Molecular Therapy, 3 (5), pp. 688-696. , DOI 10.1006/mthe.2001.0308
dc.descriptionGong, J., Chen, D., Kashiwaba, M., Kufe, D., Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells (1997) Nature Medicine, 3 (5), pp. 558-561
dc.descriptionRodriguez-Madoz, J.R., Prieto, J., Smerdou, C., Semliki forest virus vectors engineered to express higher IL-12 levels induce efficient elimination of murine colon adenocarcinomas (2005) Molecular Therapy, 12 (1), pp. 153-163. , DOI 10.1016/j.ymthe.2005.02.011, PII S152500160500081X
dc.descriptionTirapui, I., Arina, A., Mazzolinii, G., Duarte, M., Alfaroi, C., Feijoo, E., Qian, C., Melero, I., Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens (2004) International Journal of Cancer, 110 (1), pp. 51-60. , DOI 10.1002/ijc.20093
dc.descriptionGambotto, A., Tuting, T., McVey, D.L., Kovesdi, I., Tahara, H., Lotze, M.T., Robbins, P.D., Induction of antitumor immunity by direct intratumoral injection of a recombinant adenovirus vector expressing interleukin-12 (1999) Cancer Gene Therapy, 6 (1), pp. 45-53
dc.descriptionMoullier, P., Snyder, R.O., International efforts for recombinant adeno-associated viral vector reference standards (2008) Molecular Therapy, 16 (7), pp. 1185-1188. , DOI 10.1038/mt.2008.125, PII MT2008125
dc.descriptionDurocher, Y., Perret, S., Kamen, A., High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells (2002) Nucleic Acids Res, 30, pp. E9
dc.descriptionZolotukhin, S., Byrne, B.J., Mason, E., Zolotukhin, I., Potter, M., Chesnut, K., Summerford, C., Muzyczka, N., Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield (1999) Gene Therapy, 6 (6), pp. 973-985. , DOI 10.1038/sj.gt.3300938
dc.languageen
dc.publisher
dc.relationMolecular Therapy
dc.rightsfechado
dc.sourceScopus
dc.titleDevelopment Of A Liver-specific Tet-on Inducible System For Aav Vectors And Its Application In The Treatment Of Liver Cancer
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución