Lack of an Immune Response against the Tetracycline-Dependent Transactivator Correlates with Long-Term Doxycycline-Regulated Transgene Expression in Nonhuman Primates after Intramuscular Injection of Recombinant Adeno-Associated Virus
Open accessAbstract
We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, and J. M. Heard, Blood 92:1512-1517, 1998). Using the same vector harboring the cynomolgus macaque Epo cDNA instead, the present study evaluated the ability of the tetracycline-regulatable (tetR) system to establish long-term transgene regulation in nonhuman primates. The vector was administered i.m., after which 5-day induction pulses were performed monthly for up to 13 months by using doxycycline (DOX), a tetracycline analog. We show that initial inductions were successful in all individuals and that there was a tight regulation and a rapid deinduction pattern upon DOX withdrawal. For one macaque, regulation of Epo secretion was maintained during the entire experimental period; for the five remaining macaques, secreted Epo became indistinguishable from endogenous Epo upon repeated DOX inductions. We investigated the mechanism involved and showed that, except in the animal in which secretion persisted, delayed humoral and cellular immune responses were directed against the rtTA transactivator protein associated with the reduction of vector DNA in transduced muscles. This study provides some evidence that, when the immune system is not mobilized against the rtTA transactivator, the tetR-regulatable system is able to support long-term transgene regulation in the context of an rAAV in nonhuman primates. In addition, our results suggest potential improvements for vector design.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In vivo application of the Tet-On systems can be complicated by immune responses against rtTA, as reported in rodents and non-human primates.
“In vivo application of the systems can be complicated by immune responses against rtTA, as reported in rodents and non-human primates [73-78].”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [75]
The Results and Discussion report an rtTA-directed immune response in nonhuman primates that can compromise regulated transgene expression. They also say that an elaborate response against rtTA was sought but not found in murine models, so this source does not support the rodent part of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Efficient selection for high-expression transfectants with a novel eukaryotic vector
Niwa, H., Yamamura, K., & Miyazaki, J. (1991) · Gene · doi:10.1016/0378-1119(91)90434-d · Cited by 5,135 · see citing works
Tight control of gene expression in mammalian cells by tetracycline-responsive promoters.
Gossen, M., & Bujard, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.12.5547 · Cited by 4,943 · cited 1× · see citing works
“They all have in common the use of chimeric transactivators, the activity of which is controlled by drugs including tetracycline (11), mifepristone (35), ecdysone (23), and rapamycin (25).”
BackgroundDranoff, G., Jaffee, E. M., Lazenby, A., Golumbek, P. T., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D. M., & Mulligan, R. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3539 · Cited by 2,803 · see citing works
Transcriptional Activation by Tetracyclines in Mammalian Cells
Gossen, M., Freundlieb, S., Bender, G., Müller, G., Hillen, W., & Bujard, H. (1995) · Science · doi:10.1126/science.7792603 · Cited by 2,488 · see citing works
Kay, M. A., Manno, C. S., Ragni, M. V., Larson, P. J., Couto, L. B., McClelland, A., Glader, B. E., Chew, A. K., Tai, S. J., Herzog, R. W., et al. (2000) · Nature Genetics · doi:10.1038/73464 · Cited by 1,019 · see citing works
Urlinger, S., Baron, U., Thellmann, M., Hasan, M. T., Bujard, H., & Hillen, W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130192197 · Cited by 928 · see citing works
Xiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913 · see citing works
Ecdysone-inducible gene expression in mammalian cells and transgenic mice.
No, D. B., Yao, T. P., & Evans, R. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3346 · Cited by 852 · see citing works
Recombinant adeno-associated virus for muscle directed gene therapy
Fisher, K. J., Jooss, K., Alston, J., Yang, Y., Haecker, S. E., High, K., Pathak, R., Raper, S. E., & Wilson, J. M. (1997) · Nature Medicine · doi:10.1038/nm0397-306 · Cited by 654 · see citing works
Tripathy, S. K., Black, H. B., Goldwasser, E., & Leiden, J. M. (1996) · Nature Medicine · doi:10.1038/nm0596-545 · Cited by 627 · see citing works
Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., et al. (1999) · Nature Medicine · doi:10.1038/4743 · Cited by 554 · see citing works
Fisher, K. J., Gao, G. P., Weitzman, M. D., DeMatteo, R. P., Burda, J. F., & Wilson, J. M. (1996) · Journal of Virology · doi:10.1128/jvi.70.1.520-532.1996 · Cited by 546 · see citing works
A humanized system for pharmacologic control of gene expression
Rivera, V. M., Clackson, T., Natesan, S., Pollock, R. M., Amara, J. F., Keenan, T. P., Magari, S. R., Phillips, T., Courage, N. L., Cerasoli, F., et al. (1996) · Nature Medicine · doi:10.1038/nm0996-1028 · Cited by 528 · see citing works
MECHANISMS UNDERLYING EXPRESSION OF TN <i>10</i> ENCODED TETRACYCLINE RESISTANCE
Hillen, W., & Berens, C. (1994) · Annual Review of Microbiology · doi:10.1146/annurev.mi.48.100194.002021 · Cited by 511 · see citing works
Czerkinsky, C. C., Andersson, G., Ekre, H.-P. T., Nilsson, L., Klareskog, L., & Ouchterlony, Ö. (1988) · Journal of Immunological Methods · doi:10.1016/0022-1759(88)90079-8 · Cited by 495 · see citing works
Nakai, H., Yant, S. R., Storm, T. A., Fuess, S., Meuse, L., & Kay, M. A. (2001) · Journal of Virology · doi:10.1128/jvi.75.15.6969-6976.2001 · Cited by 478 · see citing works
Jooss, K., Yang, Y., Fisher, K. J., & Wilson, J. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.5.4212-4223.1998 · Cited by 470 · see citing works
Regulated Delivery of Therapeutic Proteins After in Vivo Somatic Cell Gene Transfer
Ye, X., Rivera, V. M., Zoltick, P. W., Cerasoli, F., Schnell, M. A., Gao, G., Hughes, J. V., Gilman, M. Z., & Wilson, J. M. (1999) · Science · doi:10.1126/science.283.5398.88 · Cited by 308 · see citing works
Factors Influencing Recombinant Adeno-Associated Virus Production
Salvetti, A., Orève, S., Chadeuf, G., Favre, D., Chérel, Y., Champion-Arnaud, P., David-Ameline, J., & Moullier, P. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.5-695 · Cited by 241 · see citing works
Self-citationLigand-inducible and liver-specific target gene expression in transgenic mice
Wang, Y.-L., Demayo, F., Tsai, S., & O'Malley, B. (1997) · Nature Biotechnology · doi:10.1038/nbt0397-239 · Cited by 236 · see citing works
Nakai, H., Storm, T. A., & Kay, M. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.20.9451-9463.2000 · Cited by 194 · see citing works
Long-term regulated expression of growth hormone in mice after intramuscular gene transfer
Rivera, V. M., Ye, X., Courage, N. L., Sachar, J., Cerasoli, F., Wilson, J. M., & Gilman, M. Z. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8657 · Cited by 177 · see citing works
Brockstedt, D. G., Podsakoff, G. M., Fong, L. H., Kurtzman, G. J., Mueller-Ruchholtz, W., & Engleman, E. G. (1999) · Clinical Immunology · doi:10.1006/clim.1999.4724 · Cited by 165 · see citing works
Cordier, L., Gao, G.-P., Hack, A. A., McNally, E. M., Wilson, J. M., Chirmule, N., & Sweeney, H. L. (2001) · Human Gene Therapy · doi:10.1089/104303401750061267 · Cited by 152 · see citing works
Reverse ELISPOT assay for clonal analysis of cytokine production
Nordström, I., & Ferruà, B. (1992) · Journal of Immunological Methods · doi:10.1016/0022-1759(92)90079-9 · Cited by 139 · see citing works
Bohl, D., Salvetti, A., Moullier, P., & Heard, J. M. (1998) · Blood · doi:10.1182/blood.v92.5.1512 · Cited by 136 · see citing works
Self-citationManning, W. C., Paliard, X., Zhou, S. Z., Bland, M., Lee, A. Y., Hong, K., Walker, C. M., Escobedo, J. A., & Dwarki, V. (1997) · Journal of Virology · doi:10.1128/jvi.71.10.7960-7962.1997 · Cited by 122 · see citing works
Favre, D., Provost, N., Blouin, V., Blancho, G., Chérel, Y., Salvetti, A., & Moullier, P. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0494 · Cited by 122 · see citing works
Self-citationZhang, Y., Chirmule, N., Gao, G.-P., & Wilson, J. (2000) · Journal of Virology · doi:10.1128/jvi.74.17.8003-8010.2000 · Cited by 119 · see citing works
Sarukhan, A., Camugli, S., Gjata, B., von Boehmer, H., Danos, O., & Jooss, K. U. (2001) · Journal of Virology · doi:10.1128/jvi.75.1.269-277.2001 · Cited by 119 · see citing works
Posttranslational modifications of recombinant myotube-synthesized human factor IX
Arruda, V. R., Hagstrom, J. N., Deitch, J. S., Heiman-Patterson, T. D., Camire, R. M., Chu, K. C., Fields, P. A., Herzog, R. W., Couto, L. B., Larson, P. J., et al. (2001) · Blood · doi:10.1182/blood.v97.1.130 · Cited by 116 · see citing works
Structure of Adeno-Associated Virus Vector DNA following Transduction of the Skeletal Muscle
Vincent, N., Snyder, R. O., Gluzman, R., Bohl, D., Lagarde, C., & Danos, O. (1999) · Journal of Virology · doi:10.1128/jvi.73.3.1949-1955.1999 · Cited by 112 · see citing works
Self-citationRegulation of gene expression in vivo following transduction by two separate rAAV vectors
Rendahl, K. G., Leff, S. E., Otten, G. R., Spratt, S. K., Bohl, D., Roey, M. V., Donahue, B. A., Cohen, L. K., Mandel, R. J., Danos, O., et al. (1998) · Nature Biotechnology · doi:10.1038/nbt0898-757 · Cited by 110 · see citing works
Self-citationRegulatable systems: applications in gene therapy and replicating viruses.
Agha-Mohammadi, S., & Lotze, M. T. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10027 · Cited by 79 · see citing works
Liu, Y., Santin, A. D., Mane, M., Chiriva‐Internati, M., Parham, G. P., Ravaggi, A., & Hermonat, P. L. (2000) · Journal of Interferon & Cytokine Research · doi:10.1089/107999000312702 · Cited by 63 · see citing works
Serguera, C., Bohl, D., Rolland, E., Prevost, P., & Heard, J. (1999) · Human Gene Therapy · doi:10.1089/10430349950018823 · Cited by 63 · see citing works
Self-citationSarukhan, A., Soudais, C., Danos, O., & Jooss, K. U. (2001) · The Journal of Gene Medicine · doi:10.1002/jgm.175 · Cited by 60 · see citing works
Farson, D. A., MCGUINNESS, R. P., Dull, T., Limoli, K. L., Lazar, R., Jalali, S., REDDY, S., Pennathur-Das, R., Broad, D., & Finer, M. H. (1999) · The Journal of Gene Medicine · doi:10.1002/(sici)1521-2254(199905/06)1:3 · Cited by 28 · see citing works
Overexpression of ecto-5′-nucleotidase promotes P-glycoprotein expression in renal epithelial cells
Ledoux, S., Leroy, C., Siegfried, G., Prié, D., Moullier, P., & Friedlander, G. (1997) · Kidney International · doi:10.1038/ki.1997.417 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- [14]Hillen, W., and C. Berens. 1994. Mechanisms underlying expression of Tn10-encoded tetracycline resistance. Annu. Rev. Microbiol. 48:345-369. [DOI] [PubMed] [Google Scholar]
- [31]Snyder, R. O. 1999. Adeno-associated virus-mediated gene delivery. J. Gene Med. 1:166-175. [DOI] [PubMed] [Google Scholar]
- [38]Zhang, Y., N. Chirmule, G. Gao, and J. M. Wilson. 2000. CD-40 ligand-dependent activation of cytotoxic T lymphocytes by AAV vector in vivo. J. Virol. 74:8003-8010. [DOI] [PMC free article] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Adeno-associated virus as a delivery vector for gene therapy of human diseases
Wang, J.-H., Gessler, D. J., Zhan, W., Gallagher, T. F., & Gao, G. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01780-w · Cited by 895 · see citing works
Tet-On Systems For Doxycycline-inducible Gene Expression
T. Das, A., Tenenbaum, L., & Berkhout, B. (2016) · Current Gene Therapy · doi:10.2174/1566523216666160524144041 · Cited by 434 · see citing works
“In vivo application of the systems can be complicated by immune responses against rtTA, as reported in rodents and non-human primates [73-78].”
BackgroundGene delivery by lentivirus vectors
Cockrell, A. S., & Kafri, T. (2007) · Molecular Biotechnology · doi:10.1007/s12033-007-0010-8 · Cited by 358 · see citing works
Rivera, V. M., Gao, G., Grant, R. L., Schnell, M. A., Zoltick, P. W., Rozamus, L. W., Clackson, T., & Wilson, J. M. (2004) · Blood · doi:10.1182/blood-2004-06-2501 · Cited by 272 · see citing works
Regulatable gene expression systems for gene therapy applications: progress and future challenges
Goverdhana, S., Puntel, M., Xiong, W., Zirger, J. M., Barcia, C., Curtin, J. F., Soffer, E. B., Mondkar, S., King, G. D., Hu, J., et al. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.03.022 · Cited by 283 · see citing works
Complement Is an Essential Component of the Immune Response to Adeno-Associated Virus Vectors
Zaiss, A. K., Cotter, M. J., White, L. R., Clark, S. A., Wong, N. C. W., Holers, V. M., Bartlett, J. S., & Muruve, D. A. (2008) · Journal of Virology · doi:10.1128/jvi.01990-07 · Cited by 177 · see citing works
Multidimensional control of therapeutic human cell function with synthetic gene circuits
Li, H.-S., Israni, D. V., Gagnon, K. A., Gan, K. A., Raymond, M. H., Sander, J. D., Roybal, K. T., Joung, J. K., Wong, W. W., & Khalil, A. S. (2022) · Science · doi:10.1126/science.ade0156 · Cited by 176 · see citing works
Lowenstein, P. R., Mandel, R. J., Xiong, W.-D., Kroeger, K. M., & Castro, M. G. (2007) · Current Gene Therapy · doi:10.2174/156652307782151498 · Cited by 157 · see citing works
Evaluation of Risks Related to the Use of Adeno-Associated Virus-Based Vectors
Tenenbaum, L., Lehtonen, E., & Monahan, P. E. (2003) · Current Gene Therapy · doi:10.2174/1566523034578131 · Cited by 146 · see citing works
Next-generation AAV vectors—Do not judge a virus (only) by its cover
Domenger, C., & Grimm, D. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz148 · Cited by 147 · see citing works
Immunity to CRISPR Cas9 and Cas12a therapeutics
Chew, W. L. (2017) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1408 · Cited by 146 · see citing works
Gene therapy progress and prospects: transcription regulatory systems
Toniatti, C., Bujard, H., Cortese, R., & Ciliberto, G. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302251 · Cited by 133 · see citing works
Gas-inducible transgene expression in mammalian cells and mice
Weber, W., Rimann, M., Spielmann, M., Keller, B., Baba, M. D., Aubel, D., Weber, C. C., & Fussenegger, M. (2004) · Nature Biotechnology · doi:10.1038/nbt1021 · Cited by 129 · see citing works
Lentiviral vectors for use in the central nervous system.
Jakobsson, J., & Lundberg, C. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2005.11.012 · Cited by 137 · see citing works
In vivo gene regulation using tetracycline-regulatable systems
Stieger, K., Belbellaa, B., Guiner, C. L., Moullier, P., & Rolling, F. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2008.12.016 · Cited by 128 · see citing works
Self-citationConditional control of mammalian gene expression by tetracycline-dependent hammerhead ribozymes.
Beilstein, K., Wittmann, A., Grez, M., & Suess, B. (2015) · ACS Synthetic Biology · doi:10.1021/sb500270h · Cited by 119 · see citing works
Tetracycline‐aptamer‐mediated translational regulation in yeast
Hanson, S., Berthelot, K., Fink, B., McCarthy, J. E. G., & Suess, B. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03656.x · Cited by 119 · see citing works
Autoimmune anemia in macaques following erythropoietin gene therapy
Chenuaud, P., Larcher, T., Rabinowitz, J. E., Provost, N., Chérel, Y., Casadevall, N., Samulski, R. J., & Moullier, P. (2004) · Blood · doi:10.1182/blood-2003-11-3845 · Cited by 116 · see citing works
Self-citationThe Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes
Mérienne, N., Vachey, G., de Longprez, L., Meunier, C., Zimmer, V., Perriard, G., Canales, M., Mathias, A., Herrgott, L., Beltraminelli, T., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.075 · Cited by 115 · see citing works
A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo
Zhong, G., Wang, H., He, W., Li, Y., Mou, H., Tickner, Z. J., Tran, M. H., Ou, T., Yin, Y., Diao, H., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0357-y · Cited by 113 · see citing works
Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury
Burnside, E. R., de Winter, F., Didangelos, A., James, N. D., Andreica, E.-C., Horsfall, H. L., Muir, E. M., Verhaagen, J., & Bradbury, E. J. (2018) · Brain · doi:10.1093/brain/awy158 · Cited by 113 · see citing works
Georgievska, B., Jakobsson, J., Persson, E. B., Ericson, C., Kirik, D., & Lundberg, C. (2004) · Human Gene Therapy · doi:10.1089/hum.2004.15.934 · Cited by 112 · see citing works
Stieger, K., Le Meur, G., Lasne, F., Weber, M., Deschamps, J.-Y., Nivard, D., Mendes-Madeira, A., Provost, N., Martin, L., Moullier, P., et al. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2005.12.001 · Cited by 110 · see citing works
Self-citationTuszynski, M. H., & Blesch, A. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)46028-7 · Cited by 108 · see citing works
Toromanoff, A., Chérel, Y., Guilbaud, M., Penaud‐Budloo, M., Snyder, R. O., Haskins, M. E., Deschamps, J., Guigand, L., Podevin, G., Arruda, V. R., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.87 · Cited by 99 · see citing works
Self-citationRecombinant AAV-mediated gene transfer to the retina: gene therapy perspectives
Rolling, F. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302366 · Cited by 90 · see citing works
Weber, W. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng071 · Cited by 86 · see citing works
Lamartina, S., Silvi, L., Roscilli, G., Casimiro, D., Simon, A. J., Davies, M., Shiver, J., Rinaudo, C. D., Zampaglione, I., Fattori, E., et al. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(02)00051-5 · Cited by 75 · see citing works
Barde, I., Zanta-Boussif, M., Paisant, S., Leboeuf, M., Rameau, P., Delenda, C., & Danos, O. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2005.09.012 · Cited by 93 · see citing works
Tafuro, S., Ayuso, E., Zacchigna, S., Zentilin, L., Moimas, S., Dore, F., & Giacca, M. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp152 · Cited by 77 · see citing works
Chenuaud, P., Larcher, T., Rabinowitz, J. E., Provost, N., Joussemet, B., Bujard, H., Samulski, R. J., Moullier, P., & Favre, D. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2003.12.015 · Cited by 74 · see citing works
Self-citationRegulated lentiviral NGF gene transfer controls rescue of medial septal cholinergic neurons.
Blesch, A., Conner, J., Pfeifer, A., Gasmi, M., Ramirez, A., Britton, W. R., Alfa, R. W., Verma, I., & Tuszynski, M. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.01.007 · Cited by 67 · see citing works
Developing strategies for detection of gene doping
Baoutina, A., Alexander, I. E., Rasko, J. E. J., & Emslie, K. R. (2007) · The Journal of Gene Medicine · doi:10.1002/jgm.1114 · Cited by 68 · see citing works
Adriaansen, J., Vervoordeldonk, M. J., & Tak, P. P. (2006) · Rheumatology · doi:10.1093/rheumatology/kel047 · Cited by 65 · see citing works
Toromanoff, A., Adjali, O., Larcher, T., Hill, M., Guigand, L., Chenuaud, P., Deschamps, J., Gauthier, O., Blancho, G., Vanhove, B., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.251 · Cited by 61 · see citing works
Self-citationLamartina, S., Cimino, M., Roscilli, G., Dammassa, E., Lazzaro, D., Rota, R., Ciliberto, G., & Toniatti, C. (2007) · The Journal of Gene Medicine · doi:10.1002/jgm.1083 · Cited by 59 · see citing works
Folliot, S., Briot, D., Conrath, H., Provost, N., Chérel, Y., Moullier, P., & Rolling, F. (2003) · Journal of Gene Medicine · doi:10.1002/jgm.367 · Cited by 59 · see citing works
Self-citationProgress Toward A Nonviral Gene Therapy Protocol for The Treatment of Anemia
Sebestyén, M. G., Hegge, J., Noble, M. A., Lewis, D. L., Herweijer, H., & Wolff, J. A. (2007) · Human Gene Therapy · doi:10.1089/hum.2006.186 · Cited by 56 · see citing works
Guiner, C. L., Stieger, K., Toromanoff, A., Guilbaud, M., Mendes-Madeira, A., Devaux, M., Guigand, L., Chérel, Y., Moullier, P., Rolling, F., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102538 · Cited by 50 · see citing works
Self-citationGene therapy for autoimmune diseases: quo vadis?
Chernajovsky, Y., Gould, D., & Podhajcer, O. (2004) · Nature reviews. Immunology · doi:10.1038/nri1459 · Cited by 54 · see citing works
Weber, W. (2003) · Nucleic Acids Research · doi:10.1093/nar/gng069 · Cited by 49 · see citing works
Ginhoux, F., Turbant, S., Gross, D. A., Poupiot, J., Marais, T., Lone, Y., Lemonnier, F. A., Firat, H., Perez, N., Danos, O., et al. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.05.012 · Cited by 49 · see citing works
Control of mammalian gene expression by modulation of polyA signal cleavage at 5′ UTR
Luo, L., Jea, J. D.-Y., Wang, Y., Chao, P.-W., & Yen, L. (2024) · Nature Biotechnology · doi:10.1038/s41587-023-01989-0 · Cited by 50 · see citing works
Regulatable Gene Expression Systems for Gene Therapy
Vilaboa, N. E., & Voellmy, R. W. (2006) · Current Gene Therapy · doi:10.2174/156652306777934829 · Cited by 48 · see citing works
Timed GDNF gene therapy using an immune-evasive gene switch promotes long distance axon regeneration
Eggers, R., de Winter, F., Hoyng, S. A., Hoeben, R. C., Malessy, M. J. A., Tannemaat, M. R., & Verhaagen, J. (2018) · Brain · doi:10.1093/brain/awy340 · Cited by 47 · see citing works
Liu, Y., Okada, T., Shimazaki, K., Sheykholeslami, K., Nomoto, T., Muramatsu, S., Mizukami, H., Kume, A., Xiao, S., Ichimura, K., et al. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300379 · Cited by 46 · see citing works
Guilbaud, M., Devaux, M., Couzinié, C., Duff, J. L., Toromanoff, A., Vandamme, C., Jaulin, N., Gernoux, G., Larcher, T., Moullier, P., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.234 · Cited by 45 · see citing works
Self-citationHoyng, S., Gnavi, S., Winter, F. D., Eggers, R., Ozawa, T., Zaldumbide, A., Hoeben, R., Malessy, M., & Verhaagen, J. (2014) · Gene Therapy · doi:10.1038/gt.2014.22 · Cited by 42 · see citing works
Chtarto, A., Humbert-Claude, M., Bockstael, O., Das, A. T., Boutry, S., Breger, L. S., Klaver, B., Melas, C., Barroso-Chinea, P., Gonzalez-Hernandez, T., et al. (2016) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2016.27 · Cited by 43 · see citing works
Vectors for the treatment of autoimmune disease
Gould, D., & Favorov, P. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302018 · Cited by 43 · see citing works
Adeno-associated virus vectors and neurotoxicity—lessons from preclinical and human studies
Stone, D., Aubert, M., & Jerome, K. R. (2023) · Gene Therapy · doi:10.1038/s41434-023-00405-1 · Cited by 41 · see citing works
GDNF Gene Therapy to Repair the Injured Peripheral Nerve
Eggers, R., de Winter, F., Tannemaat, M. R., Malessy, M. J. A., & Verhaagen, J. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.583184 · Cited by 41 · see citing works
Gould, D., Bright, C., & Chernajovsky, Y. (2003) · Arthritis Research & Therapy · doi:10.1186/ar1036 · Cited by 44 · see citing works
Regulatable systemic production of monoclonal antibodies by in vivo muscle electroporation
Perez, N., Bigey, P., Scherman, D., Danos, O., Piechaczyk, M., & Pelegrín, M. (2004) · Genetic Vaccines and Therapy · doi:10.1186/1479-0556-2-2 · Cited by 39 · see citing works
Sirin, O., & Park, F. (2003) · Gene · doi:10.1016/j.gene.2003.09.006 · Cited by 39 · see citing works
Stieger, K., Mendes-Madeira, A., Meur, G. L., Weber, M., Deschamps, J., Nivard, D., Provost, N., Moullier, P., & Rolling, F. (2007) · Gene Therapy · doi:10.1038/sj.gt.3303034 · Cited by 37 · see citing works
Self-citationMeasuring Immune Responses to Recombinant AAV Gene Transfer
Martino, A. T., Herzog, R. W., Anegón, I., & Adjali, O. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-370-7_11 · Cited by 36 · see citing works
Conditional Regulation of Gene Expression by Ligand-Induced Occlusion of a MicroRNA Target Sequence
Mou, H., Zhong, G., Gardner, M. R., Wang, H., Wang, Y., Cheng, D., & Farzan, M. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.02.021 · Cited by 35 · see citing works
Xiong, W., Candolfi, M., Kroeger, K. M., Puntel, M., Mondkar, S., Larocque, D., Liu, C., Curtin, J. F., Palmer, D. J., Ng, P., et al. (2008) · Molecular Therapy · doi:10.1038/sj.mt.6300375 · Cited by 34 · see citing works
Wolff, L. J., Wolff, J. A., & Sebestyén, M. G. (2009) · Human Gene Therapy · doi:10.1089/hum.2008.088 · Cited by 34 · see citing works
Kordower, J., & Olanow, C. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2007.08.001 · Cited by 32 · see citing works
Externally-Controlled Systems for Immunotherapy: From Bench to Bedside
Tristán‐Manzano, M., Justicia-Lirio, P., Maldonado‐Pérez, N., Cortijo-Gutierréz, M., Benabdellah, K., & Martı́n, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02044 · Cited by 31 · see citing works
Chtarto, A., Bockstael, O., Tshibangu, T., Dewitte, O., Levivier, M., & Tenenbaum, L. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12065 · Cited by 32 · see citing works
Transactivator and structurally optimized inducible lentiviral vectors.
Haack, K., Cockrell, A., Ma, H., Israeli, D., Ho, S., McCown, T., & Kafri, T. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.06.109 · Cited by 38 · see citing works
Schwenter, F., Schneider, B. L., Pralong, W. F., Déglon, N., & Aebischer, P. (2004) · Human Gene Therapy · doi:10.1089/1043034041361172 · Cited by 31 · see citing works
Therapy of Anemia in Kidney Failure, Using Plasmid Encoding Erythropoietin
Richard, P., Payen, E., Chèvre, R., Zuber, J., Letrou-Bonneval, E., Beuzard, Y., & Pitard, B. (2008) · Human Gene Therapy · doi:10.1089/hum.2006.0101 · Cited by 31 · see citing works
A Drug-Tunable Gene Therapy for Broad-Spectrum Protection against Retinal Degeneration
Santiago, C. P., Keuthan, C. J., Boye, S. L., Boye, S. L., Imam, A. A., & Ash, J. D. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.07.016 · Cited by 29 · see citing works
Synthetic transcription factor engineering for cell and gene therapy
Bhatt, B., García-Díaz, P., & Wink, G. (2023) · Trends in biotechnology · doi:10.1016/j.tibtech.2023.09.010 · Cited by 27 · see citing works
Moreau, A., Vandamme, C., Segovia, M., Devaux, M., Guilbaud, M., Tilly, G., Jaulin, N., Duff, J. L., Chérel, Y., Deschamps, J., et al. (2014) · Molecular Therapy — Methods & Clinical Development · doi:10.1038/mtm.2014.28 · Cited by 27 · see citing works
Self-citationA duplex qPCR assay for human erythropoietin (EPO) transgene to control gene doping in horses
Cheung, H. W., Wong, K., Lin, V. Y. C., Wan, T. S. M., & Ho, E. N. M. (2020) · Drug Testing and Analysis · doi:10.1002/dta.2907 · Cited by 25 · see citing works
Cheng, S., Tereshchenko, J., Zimmer, V., Vachey, G., Pythoud, C., Rey, M. J., Liefhebber, J. M. P., Raina, A., Streit, F., Mazur, A., et al. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.07.017 · Cited by 25 · see citing works
Nerve surgery and gene therapy: a neurobiological and clinical perspective
Hoyng, S. A., Tannemaat, M. R., de Winter, F., Verhaagen, J., & Malessy, M. J. A. (2011) · Journal of Hand Surgery (European Volume) · doi:10.1177/1753193411420348 · Cited by 24 · see citing works
AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System
Marino, M., & Holt, M. G. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.870799 · Cited by 24 · see citing works
Lena, A. M., Giannetti, P., Sporeno, E., Ciliberto, G., & Savino, R. (2005) · The Journal of Gene Medicine · doi:10.1002/jgm.758 · Cited by 27 · see citing works
Gernoux, G., Guilbaud, M., Dubreil, L., Larcher, T., Babarit, C., Ledevin, M., Jaulin, N., Planel, P., Moullier, P., & Adjali, O. (2014) · Human Gene Therapy · doi:10.1089/hum.2014.070 · Cited by 21 · see citing works
Self-citationMoss, A. C., Doran, P. P., & Macmathuna, P. (2007) · Europe PMC (PubMed Central) · Cited by 22 · see citing works
A tetracycline expression system in combination with Sox9 for cartilage tissue engineering
Yao, Y., He, Y., Guan, Q., & Wu, Q. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.043 · Cited by 22 · see citing works
Markusic, D. M., de Waart, D. R., & Seppen, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009974 · Cited by 22 · see citing works
Methylation Status of the Adeno-Associated Virus Type 2 (AAV2)
Tóth, R., Mészáros, I., Hüser, D., Forró, B., Marton, S., Olasz, F., Bànyai, K., Heilbronn, R., & Zádori, Z. (2019) · Viruses · doi:10.3390/v11010038 · Cited by 21 · see citing works
Tascou, S., Sorensen, T. K., Glénat, V., Wang, M., Lakich, M. M., Darteil, R., Vigne, E., & Thuillier, V. (2004) · Molecular Therapy · doi:10.1016/j.ymthe.2004.02.013 · Cited by 21 · see citing works
Gene therapy for neurological disease
Tuszynski, M. H. (2003) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.3.5.815 · Cited by 21 · see citing works
Host immune responses in ex vivo approaches to cutaneous gene therapy targeted to keratinocytes
Lu, Z., & Ghazizadeh, S. (2005) · Experimental Dermatology · doi:10.1111/j.1600-0625.2005.00351.x · Cited by 21 · see citing works
Lachmann, N., Brennig, S., Pfaff, N., Schermeier, H., Dahlmann, J., Phaltane, R., Gruh, I., Modlich, U., Schambach, A., Baum, C., et al. (2012) · Gene Therapy · doi:10.1038/gt.2012.40 · Cited by 20 · see citing works
Detection of EPO gene doping in blood
Neuberger, E. W. I., Jurkiewicz, M., Moser, D., & Simon, P. D. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1347 · Cited by 21 · see citing works
Léger, A., Guiner, C. L., Nickerson, M. L., McGee, K., Ferry, N., Moullier, P., Snyder, R. O., & Penaud‐Budloo, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020881 · Cited by 20 · see citing works
Self-citationBockstael, O., Chtarto, A., Wakkinen, J., Yang, X. L., Melas, C., Levivier, M., Brotchi, J., & Tenenbaum, L. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.099 · Cited by 20 · see citing works
Moreau, A., Vicente, R., Dubreil, L., Adjali, O., Podevin, G., Jacquet, C., Deschamps, J. Y., Klatzmann, D., Chérel, Y., Taylor, N. N., et al. (2008) · Molecular Therapy · doi:10.1038/mt.2008.272 · Cited by 20 · see citing works
Self-citationHan, Y., Chang, Q. A., Virág, T., West, N. C., George, D., Castro, M. G., & Bohn, M. C. (2010) · Gene Therapy · doi:10.1038/gt.2010.6 · Cited by 19 · see citing works
Lhériteau, E., Libeau, L., Mendes-Madeira, A., Deschamps, J.-Y., Weber, M., Le Meur, G., Provost, N., Guihal, C., Moullier, P., & Rolling, F. (2010) · Molecular Therapy · doi:10.1038/mt.2010.46 · Cited by 18 · see citing works
Self-citationCheung, H. W., Wong, K., Lin, V. Y. C., Farrington, A. F., Bond, A. J., Wan, T. S. M., & Ho, E. N. M. (2022) · Drug Testing and Analysis · doi:10.1002/dta.3328 · Cited by 18 · see citing works
Gan, S. U., Fu, Z., Sia, K. C., Kon, O. L., Calne, R., & Lee, K. (2018) · The Journal of Gene Medicine · doi:10.1002/jgm.3067 · Cited by 18 · see citing works
A potentially immunologically inert derivative of the reverse tetracycline-controlled transactivator
Zaldumbide, A., Weening, S. M., Cramer, S. J., Rabelink, M. J. W. E., Verhaagen, J., & Hoeben, R. C. (2010) · Biotechnology Letters · doi:10.1007/s10529-010-0218-8 · Cited by 18 · see citing works
Prolonged regulatable expression of EPO from an HSV vector using the LAP2 promoter element
Wu, Z., Mata, M. M., & Fink, D. J. (2011) · Gene Therapy · doi:10.1038/gt.2011.188 · Cited by 16 · see citing works
Translational considerations for CNS gene therapy
Ryan, D. A., & Federoff, H. J. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.3.305 · Cited by 16 · see citing works
Heinz, N., Hennig, K., & Loew, R. (2013) · BMC Biotechnology · doi:10.1186/1472-6750-13-5 · Cited by 15 · see citing works
Aurisicchio, L., Tomassi, A. D., Monica, N. L., Ciliberto, G., Traboni, C., & Palombo, F. (2005) · Journal of Virology · doi:10.1128/jvi.79.11.6772-6780.2005 · Cited by 14 · see citing works
Ligify: Automated Genome Mining for Ligand-Inducible Transcription Factors
d’Oelsnitz, S., Love, J. D., Ellington, A. D., & Ross, D. (2024) · ACS Synthetic Biology · doi:10.1021/acssynbio.4c00372 · Cited by 13 · see citing works
Zhang, H., Yuan, Y. L., Wang, Z., Jiang, B., Zhang, C. S., Wang, Q., Xu, X. H., Dong, H., & Zhang, Z. M. (2013) · Gene Therapy · doi:10.1038/gt.2013.12 · Cited by 13 · see citing works
A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth
Alfa, R. W., Tuszynski, M. H., & Blesch, A. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22101 · Cited by 13 · see citing works
Combinatorial Antigen Targeting: Ideal T-Cell Sensing and Anti-Tumor Response
Themeli, M., & Sadelain, M. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.02.009 · Cited by 13 · see citing works
- Authors
- Favre, D., Blouin, V., Provost, N., Spisek, R., Porrot, F., Bohl, D., Marmé, F., Chérel, Y., Salvetti, A., Hurtrel, B., Heard, J.-M., Rivière, Y., & Moullier, P.
- Affiliations
- Inserm (FR)
- INSERM ERM 0105
- CNRS URA1930
- Institut Pasteur (FR)
- ZMBH, Universitaet Heidelberg, D-69120 Heidelberg, Germany
- Laboratoire d'Anatomie Pathologie, INRA UR 703, Ecole Nationale Vétérinaire, Nantes
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Moullier, Philippe
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2002-11-15
- Volume
- 76
- Issue
- 22
- Pages
- 11605-11611
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC136781
- OpenAlex
- W2150329966
- Cited by
- 150
- References
- 39
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 8 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 8 · 2013: 6 · 2012: 2
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Virology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- doxycycline induction, erythropoietin, recombinant adeno-associated virus, intramuscular injection, cynomolgus macaques, transgene expression regulation, vector design, long-term gene expression
- MeSH terms
- Dependovirus, Animals, Anti-Bacterial Agents, Antibody Formation, Doxycycline, Erythropoietin, Gene Expression Regulation, Genetic Vectors, Immunity, Cellular, Injections, Intramuscular, Macaca fascicularis, Recombination, Genetic, Tetracycline, Trans-Activators, DNA, Complementary, Transgenes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
