Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy
Open accessAbstract
In a clinical study of recombinant adeno-associated virus-2 expressing human factor IX (AAV2-FIX), we detected 2 impediments to long-term gene transfer. First, preexisting anti-AAV neutralizing antibodies (NABs) prevent vector from reaching the target tissue, and second, CD8+ T-cell responses to hepatocyte-cell surface displayed AAV-capsid–terminated FIX expression after several weeks. Because the vector is incapable of synthesizing viral proteins, a short course of immunosuppression, until AAV capsid is cleared from the transduced cells, may mitigate the host T-cell response, allowing long-term expression of FIX. To evaluate coad-ministration of immunosuppression, we studied AAV8 vector infusion in rhesus macaques, natural hosts for AAV8. We administered AAV8-FIX in 16 macaques via the hepatic artery and assessed the effects of (1) preexisting anti-AAV8 NABs, (2) a standard T-cell immunosuppressive regimen, and (3) efficacy and safety of AAV8-FIX. We found that low titers (1:5) of preexisting NABs abrogate transduction, whereas animals with undetectable NABs are safely and effectively transduced by AAV8-FIX. Coadministration of mycophenolate mofetil and tacrolimus with vector does not induce toxicity and does not impair AAV transduction or FIX synthesis. These findings enable a clinical study to assess the effects of immunomodulation on long-term FIX expression in patients with hemophilia B.
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?
Transient immunosuppression is not effective at mitigating vector neutralization by pre-existing antibodies.
“While transient immunosuppression may be a promising approach for reducing cellular immune responses to gene therapy,39–41 it is not effective at mitigating vector neutralization by pre-existing antibodies.”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [40]
The Results section on preexisting AAV8 neutralizing antibodies reports that antibodies at a titer of 1:5 neutralized the vector and prevented detectable FIX expression in rhesus macaques (page unavailable). The Discussion says the transient anti-T-cell regimen did not reliably block the antibody response to AAV capsid (page unavailable). However, the cited passages do not show a direct test of whether that regimen mitigated neutralization by antibodies already present before treatment. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn nonhuman primates, MMF combined with tacrolimus did not inhibit liver transduction of AAV8.
“when tested in combination with tacrolimus in NHPs, MMF did not inhibit liver transduction of AAV8 (45).”
From A versatile toolkit for overcoming AAV immunity (2022) · cites this paper as [45]
Pre-existing neutralizing antibody (NAb) can effectively block rAAV transduction even at low levels (1:5).
“Pre-existing neutralizing antibody (NAb) can effectively block rAAV transduction even at low levels (1:5) (6).”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [6]
No difference in AAV8-hFIX transgene expression was observed when administered with tacrolimus in NHP.
“No difference in AAV8-hFIX transgene expression was observed when administered with tacrolimus in NHP (6), highlighting the difficulties of recapitulating human immune system in mouse models.”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [6]
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
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
Manno, C. S., Pierce, G. F., Arruda, V. R., Glader, B., Ragni, M., Rasko, J. J. E., Ozelo, M. C., Hoots, K., Blatt, P., Konkle, B., et al. (2006) · Nature Medicine · doi:10.1038/nm1358 · Cited by 2,163 · see citing works
Self-citationNovel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy
Gao, G.-P., Alvira, M. R., Wang, L., Calcedo, R., Johnston, J., & Wilson, J. M. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182412299 · Cited by 1,520 · 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
Self-citationAAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B
Manno, C. S., Chew, A. J., Hutchison, S., Larson, P. J., Herzog, R. W., Arruda, V. R., Tai, S. J., Ragni, M. V., Thompson, A., Ozelo, M., et al. (2003) · Blood · doi:10.1182/blood-2002-10-3296 · Cited by 749 · see citing works
Self-citationInstitute of Laboratory Animal Resources.
Wolfle, T. L. (1995) · Cited by 620 · see citing works
Induction of Immune Tolerance to Coagulation Factor IX Antigen by In Vivo Hepatic Gene Transfer
Mingozzi, F., Liu, Y.-L., Dobrzynski, E., Kaufhold, A., Liu, J. H., Wang, Y., Arruda, V. R., High, K. A., & Herzog, R. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16887 · Cited by 466 · see citing works
Self-citationNathwani, A. C., Gray, J. T., Ng, C. Y., Zhou, J., Spence, Y., Waddington, S. N., Tuddenham, E. G. D., Kemball‐Cook, G., McIntosh, J., Boon‐Spijker, M., et al. (2005) · Blood · doi:10.1182/blood-2005-10-4035 · Cited by 421 · see citing works
Snyder, R. O., Miao, C., Meuse, L., Tubb, J., Donahue, B. A., Lin, H.-F., Stafford, D. W., Patel, S., Thompson, A. R., Nichols, T., et al. (1999) · Nature Medicine · doi:10.1038/4751 · Cited by 409 · see citing works
Thomas, C. E., Storm, T. A., Huang, Z., & Kay, M. A. (2004) · Journal of Virology · doi:10.1128/jvi.78.6.3110-3122.2004 · Cited by 358 · see citing works
Mount, J. D., Herzog, R. W., Tillson, D. M., Goodman, S. A., Robinson, N., McCleland, M. L., Bellinger, D., Nichols, T. C., Arruda, V. R., Lothrop, C. D., et al. (2002) · Blood · doi:10.1182/blood.v99.8.2670 · Cited by 339 · see citing works
Self-citationScallan, C. D., Jiang, H., Liu, T., Patarroyo-White, S., Sommer, J. M., Zhou, S., Couto, L. B., & Pierce, G. F. (2006) · Blood · doi:10.1182/blood-2005-08-3229 · Cited by 271 · see citing works
Self-citationQuantification of adeno-associated virus particles and empty capsids by optical density measurement
Sommer, J. Ü. M., Smith, P. H., Parthasarathy, S., Isaacs, J., Vijay, S., Kieran, J., Powell, S. K., McClelland, A., & Wright, J. F. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(02)00019-9 · Cited by 230 · see citing works
Self-citationDavidoff, A. M., Gray, J. T., Ng, C. Y., Zhang, Y., Zhou, J., Spence, Y., Bakar, Y., & Nathwani, A. C. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2004.12.022 · Cited by 218 · see citing works
Preclinical in vivo evaluation of pseudotyped adeno-associated virus vectors for liver gene therapy
Grimm, D., Zhou, S., Nakai, H., Thomas, C. E., Storm, T. A., Fuess, S., Matsushita, T., Allen, J. M., Surosky, R. T., Lochrie, M. A., et al. (2003) · Blood · doi:10.1182/blood-2003-02-0495 · Cited by 208 · see citing works
Self-citationTotal correction of hemophilia A mice with canine FVIII using an AAV 8 serotype
Sarkar, R., Tetreault, R., Gao, G., Wang, L., Bell, P. L., Chandler, R. J., Wilson, J. M., & Kazazian, H. H. (2003) · Blood · doi:10.1182/blood-2003-08-2954 · Cited by 201 · see citing works
Lochrie, M. A., Tatsuno, G. P., Christie, B., McDonnell, J. W., Zhou, S., Surosky, R., Pierce, G. F., & Colosi, P. (2006) · Journal of Virology · doi:10.1128/jvi.80.2.821-834.2006 · Cited by 201 · see citing works
Self-citationJiang, H., Lillicrap, D., Patarroyo-White, S. L., Liu, T., Qian, X., Scallan, C. D., Powell, S., Keller, T., McMurray, M., Labelle, A., et al. (2006) · Blood · doi:10.1182/blood-2005-12-5115 · Cited by 200 · see citing works
Self-citationBiology of AAV Serotype Vectors in Liver-Directed Gene Transfer to Nonhuman Primates
Gao, G., Lü, Y., Calcedo, R., Grant, R. L., Bell, P. L., Wang, L., Figueredo, J. M., Lock, M. W., & Wilson, J. M. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.08.017 · Cited by 170 · see citing works
Nathwani, A. C., Davidoff, A. M., Hanawa, H., Hu, Y., Hoffer, F. A., Nikanorov, A. Y., Slaughter, C. A., Ng, C. Y., Zhou, J., Lozier, J. N., et al. (2002) · Blood · doi:10.1182/blood-2002-02-0589 · Cited by 164 · see citing works
Wright, J. F., Le, T., Prado, J., Bahr-Davidson, J., Smith, P. H., Zhen, Z., Sommer, J. M., Pierce, G. F., & Qu, G. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.02.021 · Cited by 158 · see citing works
Self-citationArruda, V. R., Fields, P. A., Milner, R., Wainwright, L. M., Miguel, M. P. D., Donovan, P. J., Herzog, R. W., Nichols, T. C., Biegel, J. A., Razavi, M. K., et al. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0491 · Cited by 154 · see citing works
Self-citationJung, S., Han, I., Limaye, A., Xu, R., Gelderman, M. P., Zerfas, P. M., Kamala, T., Murray, G. J., During, M. J., Brady, R. O., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051634498 · Cited by 144 · see citing works
Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer
Dobrzynski, E., Mingozzi, F., Liu, Y.-L., Bendo, E., Cao, O., Wang, L., & Herzog, R. W. (2004) · Blood · doi:10.1182/blood-2004-03-0847 · Cited by 135 · see citing works
Self-citationHuman Factor IX Corrects the Bleeding Diathesis of Mice With Hemophilia B
Kung, S., Hagstrom, J. N., Cass, D. L., Tai, S. J., Lin, H.-F., Stafford, D. W., & High, K. A. (1998) · Blood · doi:10.1182/blood.v91.3.784 · Cited by 129 · see citing works
Self-citationLozier, J. N., Metzger, M. E., Donahue, R. E., & Morgan, R. A. (1999) · Blood · doi:10.1182/blood.v94.12.3968.424k43_3968_3975 · Cited by 118 · see citing works
Lebherz, C., Gao, G., Louboutin, J., Millar, J. S., Rader, D. J., & Wilson, J. M. (2004) · The Journal of Gene Medicine · doi:10.1002/jgm.554 · Cited by 98 · see citing works
Ding, Z., Georgiev, P., & Thöny, B. (2005) · Gene Therapy · doi:10.1038/sj.gt.3302684 · Cited by 85 · see citing works
Conlon, T., Cossette, T. L., Erger, K. E., Choi, Y.-K., Clarke, T., Scott-Jorgensen, M., Song, S.-H., Campbell-Thompson, M., Crawford, J., & Flotte, T. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.05.016 · Cited by 60 · see citing works
Beaty, R. M., Jackson, M., Peterson, D., Bird, A., Brown, T. T., Benjamin, D. K., Juopperi, T. A., Kishnani, P. S., Boney, A., Chen, Y.-T., et al. (2002) · Gene Therapy · doi:10.1038/sj.gt.3301728 · Cited by 54 · see citing works
The Rhesus Macaque as an Animal Model for Hemophilia B Gene Therapy
Lozier, J. N., Metzger, M. E., Donahue, R. E., & Morgan, R. A. (1999) · Blood · doi:10.1182/blood.v93.6.1875.406k16_1875_1881 · Cited by 32 · see citing works
Hodges, B. L., Taylor, K. M., Chu, Q., Scull, S. E., Serriello, R. G., Anderson, S. C., Wang, F., & Scheule, R. K. (2005) · Molecular Therapy · doi:10.1016/j.ymthe.2005.06.475 · Cited by 20 · see citing works
Vincenti, F. G., & Stock, P. G. (2003) · Transplantation Proceedings · doi:10.1016/s0041-1345(03)00237-9 · Cited by 18 · see citing works
AAV-mediated gene therapy for hemophilia.
Couto, L. B., & Pierce, G. F. (2003) · PubMed · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Boutin, S., Monteilhet, V., Veron, P., Leborgne, C., Benveniste, O., Montus, M. F., & Masurier, C. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.182 · Cited by 970 · see citing works
Immune responses to AAV vectors: overcoming barriers to successful gene therapy
Mingozzi, F., & High, K. A. (2013) · Blood · doi:10.1182/blood-2013-01-306647 · Cited by 955 · see citing works
Self-citationEmerging issues in AAV-mediated in vivo gene therapy
Colella, P., Ronzitti, G., & Mingozzi, F. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.11.007 · Cited by 881 · see citing works
Self-citationTherapeutic in vivo gene transfer for genetic disease using AAV: Progress and challenges
Mingozzi, F., & High, K. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2988 · Cited by 893 · see citing works
Self-citationAAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer
Costa Verdera, H., Kuranda, K., & Mingozzi, F. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2019.12.010 · Cited by 641 · see citing works
Self-citationGray, S. J., Matagne, V., Bachaboina, L., Yadav, S., Ojeda, S. R., & Samulski, R. J. (2011) · Molecular Therapy · doi:10.1038/mt.2011.72 · Cited by 501 · see citing works
Selection and evaluation of clinically relevant AAV variants in a xenograft liver model
Lisowski, L., Dane, A. P., Chu, K., Zhang, Y., Cunningham, S. C., Wilson, E. M., Nygaard, S., Grompe, M., Alexander, I. E., & Kay, M. A. (2014) · Nature · doi:10.1038/nature12875 · Cited by 450 · see citing works
Gaudet, D., Méthot, J., Déry, S., Brisson, D., Essiembre, C., Tremblay, G., Tremblay, K., de Wal, J., Twisk, J., van den Bulk, N., et al. (2013) · Gene Therapy · doi:10.1038/gt.2012.43 · Cited by 404 · see citing works
Human Immune Responses to Adeno-Associated Virus (AAV) Vectors
Ronzitti, G., Gross, D.-A., & Mingozzi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00670 · Cited by 357 · see citing works
Self-citationOvercoming Preexisting Humoral Immunity to AAV Using Capsid Decoys
Mingozzi, F., Anguela, X. M., Pavani, G., Chen, Y., Davidson, R. J., Hui, D. J., Yazicioglu, M., Elkouby, L., Hinderer, C. J., Faella, A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005795 · Cited by 355 · see citing works
Self-citationAdeno-Associated Virus Antibody Profiles in Newborns, Children, and Adolescents
Calcedo, R., Morizono, H., Wang, L., McCarter, R., He, J., Jones, D., Batshaw, M. L., & Wilson, J. M. (2011) · Clinical and Vaccine Immunology · doi:10.1128/cvi.05107-11 · Cited by 345 · see citing works
Leborgne, C., Barbon, E., Alexander, J. M., Hanby, H., Delignat, S., Cohen, D. M., Collaud, F., Muraleetharan, S., Lupo, D., Silverberg, J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0911-7 · Cited by 336 · see citing works
Self-citationMingozzi, F., Meulenberg, J. J., Hui, D. J., Basner-Tschakarjan, E., Hasbrouck, N. C., Edmonson, S. A., Hutnick, N. A., Betts, M. R., Kastelein, J. J., Stroes, E. S., et al. (2009) · Blood · doi:10.1182/blood-2008-07-167510 · Cited by 295 · see citing works
Self-citationCukras, C., Wiley, H. E., Jeffrey, B. G., Sen, H. N., Turriff, A., Zeng, Y., Vijayasarathy, C., Marangoni, D., Ziccardi, L., Kjellstrom, S., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.025 · Cited by 268 · see citing works
Meliani, A., Boisgerault, F., Hardet, R., Marmier, S., Collaud, F., Ronzitti, G., Leborgne, C., Costa Verdera, H., Simon Sola, M., Charles, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06621-3 · Cited by 265 · see citing works
Self-citationMingozzi, F., Hasbrouck, N. C., Basner-Tschakarjan, E., Edmonson, S. A., Hui, D. J., Sabatino, D. E., Zhou, S., Wright, J. F., Jiang, H., Pierce, G. F., et al. (2007) · Blood · doi:10.1182/blood-2007-03-080093 · Cited by 254 · see citing works
Self-citationBucher, K., Rodríguez-Bocanegra, E., Dauletbekov, D., & Fischer, M. D. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100915 · Cited by 242 · see citing works
Humoral immune response to AAV
Calcedo, R., & Wilson, J. M. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00341 · Cited by 243 · see citing works
Unraveling the complex story of immune responses to AAV vectors trial after trial.
Vandamme, C., Adjali, O., & Mingozzi, F. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.150 · Cited by 234 · see citing works
Self-citationWhole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy
Haurigot, V., Marcó, S., Ribera, A., Garcia, M., Ruzo, A., Villacampa, P., Ayuso, E., Añor, S., Andaluz, A., Pineda, M., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66778 · Cited by 215 · see citing works
Self-citationOvercoming innate immune barriers that impede AAV gene therapy vectors
Muhuri, M., Maeda, Y., Ma, H., Ram, S., Fitzgerald, K. A., Tai, P. W. L., & Gao, G. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143780 · Cited by 212 · see citing works
Li, C., Narkbunnam, N., Samulski, R. J., Asokan, A., Hu, G., Jacobson, L. J., Manco-Johnson, M. J., Monahan, P. E., & The Joint Outcome Study Investigators (2012) · Gene Therapy · doi:10.1038/gt.2011.90 · Cited by 225 · see citing works
Wang, L., Calcedo, R., Bell, P., Lin, J., Grant, R. L., Siegel, D. L., & Wilson, J. M. (2011) · Human Gene Therapy · doi:10.1089/hum.2011.031 · Cited by 212 · see citing works
Mingozzi, F., & High, K. A. (2017) · Annual Review of Virology · doi:10.1146/annurev-virology-101416-041936 · Cited by 206 · see citing works
Self-citationMonteilhet, V., Saheb, S., Boutin, S., Leborgne, C., Veron, P., Montus, M.-F., Moullier, P., Benveniste, O., & Masurier, C. (2011) · Molecular Therapy · doi:10.1038/mt.2011.108 · Cited by 206 · see citing works
Influence of Pre-existing Anti-capsid Neutralizing and Binding Antibodies on AAV Vector Transduction
Fitzpatrick, Z., Leborgne, C., Barbon, E., Masat, E., Ronzitti, G., van Wittenberghe, L., Vignaud, A., Collaud, F., Charles, S., Simon Sola, M., et al. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2018.02.003 · Cited by 192 · see citing works
Self-citationMultifunctional CRISPR-Cas9 with Engineered Immunosilenced Human T Cell Epitopes
Ferdosi, S. R., Ewaisha, R., Moghadam, F., Krishna, S., Park, J. G., Ebrahimkhani, M. R., Kiani, S., & Anderson, K. S. (2019) · Nature Communications · doi:10.1038/s41467-019-09693-x · Cited by 204 · see citing works
Konkle, B. A., Walsh, C. E., Escobar, M. A., Josephson, N. C., Young, G., von Drygalski, A., McPhee, S. W. J., Samulski, R. J., Bilic, I., de la Rosa, M., et al. (2021) · Blood · doi:10.1182/blood.2019004625 · Cited by 189 · see citing works
Pien, G. C., Basner-Tschakarjan, E., Hui, D. J., Mentlik, A. N., Finn, J. D., Hasbrouck, N. C., Zhou, S., Murphy, S. L., Maus, M. V., Mingozzi, F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36891 · Cited by 192 · see citing works
Self-citationAdeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery
Nidetz, N. F., McGee, M. C., Tse, L. V., Li, C., Cong, L., Li, Y., & Huang, W. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107453 · Cited by 174 · see citing works
rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis
Shen, W., Liu, S., & Ou, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1001263 · Cited by 173 · see citing works
Kotterman, M. A., Yin, L., Strazzeri, J. M., Flannery, J. G., Merigan, W. H., & Schaffer, D. V. (2015) · Gene Therapy · doi:10.1038/gt.2014.115 · Cited by 169 · see citing works
Neutralizing antibodies against AAV serotypes 1, 2, 6, and 9 in sera of commonly used animal models
Rapti, K., Louis-Jeune, V., Kohlbrenner, E., Ishikawa, K., Ladage, D., Zolotukhin, S., Hajjar, R. J., & Weber, T. (2012) · Molecular Therapy · doi:10.1038/mt.2011.177 · Cited by 170 · see citing works
György, B., Fitzpatrick, Z., Crommentuijn, M. H. W., Mu, D., & Maguire, C. A. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.05.032 · Cited by 153 · see citing works
Sutaria, D. S., Badawi, M., Phelps, M. A., & Schmittgen, T. D. (2017) · Pharmaceutical Research · doi:10.1007/s11095-017-2123-5 · Cited by 140 · see citing works
Adeno-Associated Virus Gene Therapy for Liver Disease
Kattenhorn, L. M., Tipper, C. H., Stoica, L., Geraghty, D. S., Wright, T. L., Clark, K. R., & Wadsworth, S. C. (2016) · Human Gene Therapy · doi:10.1089/hum.2016.160 · Cited by 138 · see citing works
Mingozzi, F., Chen, Y., Edmonson, S. C., Zhou, S., Thurlings, R. M., Tak, P. P., High, K. A., & Vervoordeldonk, M. J. (2013) · Gene Therapy · doi:10.1038/gt.2012.55 · Cited by 138 · see citing works
Self-citationFerreira, V., Twisk, J., Kwikkers, K., Aronica, E., Brisson, D., Methot, J., Petry, H., & Gaudet, D. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.169 · Cited by 137 · see citing works
The Pleiotropic Effects of Natural AAV Infections on Liver-directed Gene Transfer in Macaques
Wang, L., Calcedo, R., Wang, H., Bell, P., Grant, R., Vandenberghe, L. H., Sanmiguel, J., Morizono, H., Batshaw, M. L., & Wilson, J. M. (2010) · Molecular Therapy · doi:10.1038/mt.2009.245 · Cited by 130 · see citing works
Meliani, A., Boisgerault, F., Fitzpatrick, Z., Marmier, S., Leborgne, C., Collaud, F., Simon Sola, M., Charles, S., Ronzitti, G., Vignaud, A., et al. (2017) · Blood Advances · doi:10.1182/bloodadvances.2017010181 · Cited by 127 · see citing works
Self-citationMajowicz, A., Nijmeijer, B., Lampen, M. H., Spronck, L., de Haan, M., Petry, H., van Deventer, S. J., Meyer, C., Tangelder, M., & Ferreira, V. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.05.009 · Cited by 126 · see citing works
Mendell, J. R., Connolly, A. M., Lehman, K. J., Griffin, D. A., Khan, S. Z., Dharia, S. D., Quintana-Gallardo, L., & Rodino-Klapac, L. R. (2022) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2022.02.011 · Cited by 124 · see citing works
Corti, M., Liberati, C., Smith, B. K., Lawson, L. A., Tuna, I. S., Conlon, T. J., Coleman, K. E., Islam, S., Herzog, R. W., Fuller, D. D., et al. (2017) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.146 · Cited by 120 · see citing works
Immune responses to AAV-vectors, the Glybera example from bench to bedside
Ferreira, V., Petry, H., & Salmon, F. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00082 · Cited by 120 · see citing works
Mingozzi, F., Chen, Y., Murphy, S. L., Edmonson, S. C., Tai, A., Price, S. D., Metzger, M. E., Zhou, S., Wright, J. F., Donahue, R. E., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2012.84 · Cited by 112 · see citing works
Self-citationEnhancing the Clinical Potential of AAV Vectors by Capsid Engineering to Evade Pre-Existing Immunity
Bartel, M. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00204 · Cited by 108 · see citing works
Exposure to wild-type AAV drives distinct capsid immunity profiles in humans
Kuranda, K., Jean-Alphonse, P., Leborgne, C., Hardet, R., Collaud, F., Marmier, S., Costa Verdera, H., Ronzitti, G., Veron, P., & Mingozzi, F. (2018) · Journal of Clinical Investigation · doi:10.1172/jci122372 · Cited by 104 · see citing works
Self-citationImmunology of AAV-Mediated Gene Transfer in the Eye
Willett, K., & Bennett, J. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00261 · Cited by 105 · see citing works
Diverse IgG subclass responses to adeno‐associated virus infection and vector administration
Murphy, S. L., Li, H., Mingozzi, F., Sabatino, D. E., Hui, D. J., Edmonson, S. A., & High, K. A. (2009) · Journal of Medical Virology · doi:10.1002/jmv.21360 · Cited by 101 · see citing works
Self-citationCapsid-specific removal of circulating antibodies to adeno-associated virus vectors
Bertin, B., Veron, P., Leborgne, C., Deschamps, J.-Y., Moullec, S., Fromes, Y., Collaud, F., Boutin, S., Latournerie, V., van Wittenberghe, L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-57893-z · Cited by 100 · see citing works
Self-citationImmune Response Mechanisms against AAV Vectors in Animal Models
Martino, A. T., & Markusic, D. M. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.12.008 · Cited by 97 · see citing works
Lin, S.-W., Hensley, S. E., Tatsis, N., Lasaro, M. O., & Ertl, H. C. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33138 · Cited by 88 · see citing works
Veron, P., Leborgne, C., Monteilhet, V., Boutin, S., Martin, S., Moullier, P., & Masurier, C. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200620 · Cited by 88 · see citing works
Age-Related Seroprevalence of Antibodies Against AAV-LK03 in a UK Population Cohort
Perocheau, D. P., Cunningham, S. C., Lee, J., Antinao Diaz, J., Waddington, S. N., Gilmour, K., Eaglestone, S., Lisowski, L., Thrasher, A. J., Alexander, I. E., et al. (2019) · Human Gene Therapy · doi:10.1089/hum.2018.098 · Cited by 81 · see citing works
The impact of pre-existing immunity on the non-clinical pharmacodynamics of AAV5-based gene therapy
Long, B. R., Sandza, K., Holcomb, J., Crockett, L., Hayes, G. M., Arens, J., Fonck, C., Tsuruda, L. S., Schweighardt, B., O’Neill, C. A., et al. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.03.006 · Cited by 75 · see citing works
Unzu, C., Hervás-Stubbs, S., Sampedro, A., Mauleón, I., Mancheño, U., Alfaro, C., de Salamanca, R. E., Benito, A., Beattie, S. G., Petry, H., et al. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-122 · Cited by 69 · see citing works
Strategies to circumvent humoral immunity to adeno-associated viral vectors
Tse, L. V., Moller-Tank, S., & Asokan, A. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1035645 · Cited by 61 · see citing works
Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies
Chu, W. S., & Ng, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.658038 · Cited by 59 · see citing works
Salas, D., Kwikkers, K. L., Zabaleta, N., Bazo, A., Petry, H., van Deventer, S. J., Aseguinolaza, G. G., & Ferreira, V. (2019) · Blood Advances · doi:10.1182/bloodadvances.2019000380 · Cited by 59 · see citing works
Barker, S. E., Broderick, C. A., Robbie, S. J., Duran, Y., Natkunarajah, M., Buch, P., Balaggan, K. S., MacLaren, R. E., Bainbridge, J. W. B., Smith, A. J., et al. (2009) · The Journal of Gene Medicine · doi:10.1002/jgm.1327 · Cited by 59 · see citing works
MyD88 Signaling in B Cells Regulates the Production of Th1-dependent Antibodies to AAV
Sudres, M., Ciré, S., Vasseur, V., Brault, L., Da Rocha, S., Boisgérault, F., Le Bec, C., Gross, D. A., Blouin, V., Ryffel, B., et al. (2012) · Molecular Therapy · doi:10.1038/mt.2012.101 · Cited by 59 · see citing works
Recommendations for the Development of Cell-Based Anti-Viral Vector Neutralizing Antibody Assays
Gorovits, B., Fiscella, M., Havert, M., Koren, E., Long, B., Milton, M., & Purushothama, S. (2020) · The AAPS Journal · doi:10.1208/s12248-019-0403-1 · Cited by 57 · see citing works
A versatile toolkit for overcoming AAV immunity
Li, X., Wei, X., Lin, J., & Ou, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991832 · Cited by 57 · see citing works
Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes
Hui, D. J., Basner-Tschakarjan, E., Chen, Y., Davidson, R. J., Buchlis, G., Yazicioglu, M., Pien, G. C., Finn, J. D., Haurigot, V., Tai, A., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.166 · Cited by 47 · see citing works
Self-citationIlyinskii, P. O., Michaud, A. M., Rizzo, G. L., Roy, C. J., Leung, S. S., Elkins, S. L., Capela, T., Chowdhury, A., Li, L., Chandler, R. J., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.06.015 · Cited by 39 · see citing works
Complement Activation by Adeno-Associated Virus-Neutralizing Antibody Complexes
West, C., Federspiel, J. D., Rogers, K., Khatri, A., Rao-Dayton, S., Ocana, M. F., Lim, S., D'Antona, A. M., Casinghino, S., & Somanathan, S. (2023) · Human Gene Therapy · doi:10.1089/hum.2023.018 · Cited by 39 · see citing works
Mycophenolate mofetil impairs transduction of single-stranded adeno-associated viral vectors
Montenegro-Miranda, P. S., Bloemendaal, L. T., Kunne, C., de Waart, D. R., & Bosma, P. J. (2011) · Human Gene Therapy · doi:10.1089/hum.2010.222 · Cited by 35 · see citing works
Obstacles and future of gene therapy for hemophilia
Arruda, V. R., & Samelson-Jones, B. J. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2015.1069179 · Cited by 33 · see citing works
Ocular Inflammation and Treatment Emergent Adverse Events in Retinal Gene Therapy
Mehta, N., Robbins, D. A., & Yiu, G. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000366 · Cited by 33 · see citing works
Cramer, M. L., Shao, G., Rodino-Klapac, L. R., Chicoine, L. G., & Martin, P. T. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.113 · Cited by 22 · see citing works
Superior human hepatocyte transduction with adeno-associated virus vector serotype 7
Shao, W., Pei, X., Cui, C., Askew, C., Dobbins, A., Chen, X., Abajas, Y. L., Gerber, D. A., Samulski, R. J., Nichols, T. C., et al. (2019) · Gene Therapy · doi:10.1038/s41434-019-0104-5 · Cited by 22 · see citing works
Korpela, H., Lampela, J., Airaksinen, J., Järveläinen, N., Siimes, S., Valli, K., Nieminen, T., Turunen, M., Grönman, M., Saraste, A., et al. (2022) · Gene Therapy · doi:10.1038/s41434-022-00322-9 · Cited by 22 · see citing works
Kotterman, M., Beliakoff, G., Croze, R., Vazin, T., Schmitt, C., Szymanski, P., Leong, M., Quezada, M., Holt, J., Barglow, K., et al. (2021) · doi:10.1101/2021.06.24.449775 · Cited by 20 · see citing works
Stolte, B., Schreiber-Katz, O., Günther, R., Wurster, C. D., Petri, S., Osmanovic, A., Freigang, M., Uzelac, Z., Leo, M., von Velsen, O., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.054 · Cited by 15 · see citing works
Haar, J., Blazevic, D., Strobel, B., Kreuz, S., & Michelfelder, S. (2022) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2022.04.008 · Cited by 11 · see citing works
- Authors
- Jiang, H., Couto, L. B., Patarroyo-White, S., Liu, T., Nagy, D., Vargas, J. A., Zhou, S., Scallan, C. D., Sommer, J., Vijay, S., Mingozzi, F., High, K. A., & Pierce, G. F.
- Affiliations
- Children's Hospital of Philadelphia (US)
- From Avigen Inc, Alameda, CA; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; and Howard Hughes Medical Institute, Children's Hospital of Philadelphia, Philadelphia, PA.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-11-15
- Volume
- 108
- Issue
- 10
- Pages
- 3321-3328
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1895424
- OpenAlex
- W2067204822
- Cited by
- 330
- References
- 34
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 17 · 2023: 22 · 2022: 24 · 2021: 21 · 2020: 19 · 2019: 21 · 2018: 16 · 2017: 18 · 2016: 8 · 2015: 25 · 2014: 12 · 2013: 15 · 2012: 24
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bayer HealthCare
- National Institutes of Health
- National Heart, Lung, and Blood Institute (U01HL066948, P01HL078810, U01-HL66948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- adeno-associated virus, AAV8, factor IX, hemophilia B, liver-directed gene transfer, immunosuppression, CD8+ T cell responses, mycophenolate mofetil, tacrolimus, hepatic artery infusion, rhesus monkeys, long-term gene expression, gene therapy
- MeSH terms
- Dependovirus, Animals, Antibodies, Hemophilia B, Drug Therapy, Combination, Factor IX, Genetic Vectors, Humans, Immunosuppression Therapy, Liver, Macaca mulatta, Male, Mycophenolic Acid, Organ Specificity, Genetic Therapy, Tacrolimus, Gene Transfer Techniques, Mice
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