The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Adenovirus-Associated Virus Vector–Mediated Gene Transfer in Hemophilia B
Open accessAbstract
BACKGROUND: Hemophilia B, an X-linked disorder, is ideally suited for gene therapy. We investigated the use of a new gene therapy in patients with the disorder. METHODS: We infused a single dose of a serotype-8-pseudotyped, self-complementary adenovirus-associated virus (AAV) vector expressing a codon-optimized human factor IX (FIX) transgene (scAAV2/8-LP1-hFIXco) in a peripheral vein in six patients with severe hemophilia B (FIX activity, <1% of normal values). Study participants were enrolled sequentially in one of three cohorts (given a high, intermediate, or low dose of vector), with two participants in each group. Vector was administered without immunosuppressive therapy, and participants were followed for 6 to 16 months. RESULTS: AAV-mediated expression of FIX at 2 to 11% of normal levels was observed in all participants. Four of the six discontinued FIX prophylaxis and remained free of spontaneous hemorrhage; in the other two, the interval between prophylactic injections was increased. Of the two participants who received the high dose of vector, one had a transient, asymptomatic elevation of serum aminotransferase levels, which was associated with the detection of AAV8-capsid-specific T cells in the peripheral blood; the other had a slight increase in liver-enzyme levels, the cause of which was less clear. Each of these two participants received a short course of glucocorticoid therapy, which rapidly normalized aminotransferase levels and maintained FIX levels in the range of 3 to 11% of normal values. CONCLUSIONS: Peripheral-vein infusion of scAAV2/8-LP1-hFIXco resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, with few side effects. Although immune-mediated clearance of AAV-transduced hepatocytes remains a concern, this process may be controlled with a short course of glucocorticoids without loss of transgene expression. (Funded by the Medical Research Council and others; ClinicalTrials.gov number, NCT00979238.).
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“the presence of pre-existing antibodies has been correlated with decreased efficacy of gene therapy in clinical trials where the route of administration exposes vector to serum.26,30,31”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [30]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“NABs are often the most commonly invoked exclusion criterion for patent enrollment.30”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [30]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“liver-directed therapies resulting in liver transaminase elevation, which coincides with decreased factor IX (FIX) transgene expression, likely due to AAV capsid-specific cytotoxic T cells destroying transduced hepatocytes (12, 13).”
From Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses (2021) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“As a result, AAV clinical successes to date have involved delivery either to immune privileged regions or to subjects lacking apparent AAV immunological memory.8–14,30,42”
From Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates (2015) · cites this paper as [30]
In the citing paper
“Finally, certain host responses have only been observed with very high doses of intravenous AAV, suggesting a threshold effect for these host reactions [19–21].”
From Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer (2023) · cites this paper as [21]
In the citing paper
“Moreover, administration of intermediate doses of AAV resulted in detectable circulating capsid-specific T cells but transaminase elevation and loss of transgene expression were not observed [21].”
From Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer (2023) · cites this paper as [21]
In the citing paper
“In summary, the transgene immune response is mostly observed in patients with no residual protein expression; therefore, clinical studies preferably choose subjects with missense mutation or subjects with no response in protein replacement therapy [21, 24].”
From Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer (2023) · cites this paper as [21]
In the citing paper
“Antibody formation against capsid was also not impacted by CpG depletion in clinical trials (19, 57).”
From Effect of CpG Depletion of Vector Genome on CD8+ T Cell Responses in AAV Gene Therapy (2021) · cites this paper as [57]
In the citing paper
“This led to the requirement for immunosuppression to maintain transgene expression in patients treated with AAVs, further complicating the therapeutic impact.”
From Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells (2021) · cites this paper as [6]
In the citing paper
“CCS are used short-term in conjunction with systemically delivered gene therapies to negate transaminitis and associated CTL-induced injury transgene loss (30, 65), and reduce T-cell infiltrates in muscular fibers in non-human primates (NHP) (33).”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [65]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
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
Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses
Calcedo, R., Vandenberghe, L. H., Gao, G., Lin, J., & Wilson, J. M. (2009) · The Journal of Infectious Diseases · doi:10.1086/595830 · Cited by 808
Cd8(+) T-Cell Responses to Adeno-Associated Virus Capsid in Humans
Mingozzi, F., Maus, M. V., Hui, D. J., Sabatino, D. E., Murphy, S. L., Rasko, J. E. J., Ragni, M. V., Manno, C. S., Sommer, J., Jiang, H., et al. (2007) · Nature Medicine · doi:10.1038/nm1549 · Cited by 748
Self-citationDystrophin Immunity in Duchenne's Muscular Dystrophy
Mendell, J. R., Campbell, K., Rodino-Klapac, L., Sahenk, Z., Shilling, C., Lewis, S., Bowles, D., Gray, S., Li, C., Galloway, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000228 · Cited by 655
Sawa, A., Wiegand, G. W., Cooper, J. K., Margolis, R. L., Sharp, A. H., Lawler, J. F., Greenamyre, J. T., Snyder, S. H., & Ross, C. A. (1999) · Nature Medicine · doi:10.1038/13518 · Cited by 557
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
Self-citationDarby, S. C., Kan, S. W., Spooner, R. J. D., Giangrande, P. L. F., Hill, F. G. H., Hay, C. R. M., Lee, C. A., Ludlam, C. A., & Williams, M. (2007) · Blood · doi:10.1182/blood-2006-10-050435 · Cited by 511
Nathwani, 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 419
Self-citationSnyder, 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
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444
Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018) · Science · doi:10.1126/science.aan4672 · Cited by 1,410
Self-citationViral vector platforms within the gene therapy landscape
Bulcha, J. T., Wang, Y., Ma, H., Tai, P. W. L., & Gao, G. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00487-6 · Cited by 1,404
Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B
Nathwani, A. C., Reiss, U. M., Tuddenham, E. G. D., Rosales, C., Chowdary, P., McIntosh, J., Della Peruta, M., Lheriteau, E., Patel, N., Raj, D., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407309 · Cited by 1,273
Self-citationEngineering adeno-associated virus vectors for gene therapy
Li, C., & Samulski, R. J. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-019-0205-4 · Cited by 1,175
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
Self-citationGene therapy clinical trials worldwide to 2017: An update
Ginn, S. L., Amaya, A. K., Alexander, I. E., Edelstein, M., & Abedi, M. R. (2018) · The Journal of Gene Medicine · doi:10.1002/jgm.3015 · Cited by 903
Emerging 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
Self-citationHinderer, C., Katz, N., Buza, E. L., Dyer, C., Goode, T., Bell, P., Richman, L. K., & Wilson, J. M. (2018) · Human Gene Therapy · doi:10.1089/hum.2018.015 · Cited by 814
Immune Responses to Viral Gene Therapy Vectors
Shirley, J. L., de Jong, Y. P., Terhorst, C., & Herzog, R. W. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.01.001 · Cited by 788
Hemophilia B Gene Therapy with a High-Specific-Activity Factor IX Variant
George, L. A., Sullivan, S. K., Giermasz, A., Rasko, J. E. J., Samelson-Jones, B. J., Ducore, J., Cuker, A., Sullivan, L. M., Majumdar, S., Teitel, J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1708538 · Cited by 762
Self-citationEngineering adeno-associated viruses for clinical gene therapy
Kotterman, M. A., & Schaffer, D. V. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3742 · Cited by 761
Current clinical applications of in vivo gene therapy with AAVs
Mendell, J. R., Al-Zaidy, S. A., Rodino-Klapac, L. R., Goodspeed, K., Gray, S. J., Kay, C. N., Boye, S. L., Boye, S. E., George, L. A., Salabarria, S., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2020.12.007 · Cited by 743
AAV5–Factor VIII Gene Transfer in Severe Hemophilia A
Rangarajan, S., Walsh, L., Lester, W., Perry, D., Madan, B., Laffan, M., Yu, H., Vettermann, C., Pierce, G. F., Wong, W. Y., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1708483 · Cited by 694
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
Self-citationHigh, K. A., & Roncarolo, M. G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1706910 · Cited by 555
Self-citationAn essential receptor for adeno-associated virus infection
Pillay, S., Meyer, N. L., Puschnik, A. S., Davulcu, O., Diep, J., Ishikawa, Y., Jae, L. T., Wosen, J. E., Nagamine, C. M., Chapman, M. S., et al. (2016) · Nature · doi:10.1038/nature16465 · Cited by 532
The past and future of haemophilia: diagnosis, treatments, and its complications
Peyvandi, F., Garagiola, I., & Young, G. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01123-x · Cited by 505
Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas
Nault, J.-C., Datta, S., Imbeaud, S., Franconi, A., Mallet, M., Couchy, G., Letouzé, E., Pilati, C., Verret, B., Blanc, J.-F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3389 · Cited by 489
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
Self-citationMendell, J. R., Sahenk, Z., Lehman, K., Nease, C., Lowes, L. P., Miller, N. F., Iammarino, M. A., Alfano, L. N., Nicholl, A., Al-Zaidy, S., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1484 · Cited by 405
Immunogenicity and toxicity of AAV gene therapy
Ertl, H. C. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.975803 · Cited by 402
Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy
Chandler, R. J., LaFave, M. C., Varshney, G. K., Trivedi, N. S., Carrillo-Carrasco, N., Senac, J. S., Wu, W., Hoffmann, V., Elkahloun, A. G., Burgess, S. M., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79213 · Cited by 403
Extracellular Metabolic Energetics Can Promote Cancer Progression
Loo, J. M., Scherl, A., Nguyen, A., Man, F. Y., Weinberg, E., Zeng, Z., Saltz, L., Paty, P. B., & Tavazoie, S. F. (2015) · Cell · doi:10.1016/j.cell.2014.12.018 · Cited by 393
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
Self-citationPre-existing Anti–Adeno-Associated Virus Antibodies as a Challenge in AAV Gene Therapy
Louis Jeune, V., Joergensen, J. A., Hajjar, R. J., & Weber, T. (2013) · Human Gene Therapy Methods · doi:10.1089/hgtb.2012.243 · Cited by 358
Overcoming 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
Self-citationWang, D., Mou, H., Li, S., Li, Y., Hough, S., Tran, K., Li, J., Yin, H., Anderson, D. G., Sontheimer, E. J., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2015.087 · Cited by 345
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear
Landegger, L. D., Pan, B., Askew, C., Wassmer, S. J., Gluck, S. D., Galvin, A., Taylor, R., Forge, A., Stankovic, K. M., Holt, J. R., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3781 · Cited by 325
Keeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322
In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector
Zinn, E., Pacouret, S., Khaychuk, V., Turunen, H. T., Carvalho, L. S., Andres-Mateos, E., Shah, S., Shelke, R., Maurer, A. C., Plovie, E., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.019 · Cited by 310
Gene Therapy With Adeno-Associated Virus Vector 5-Human Factor IX in Adults With Hemophilia B
Miesbach, W., Meijer, K., Coppens, M., Kampmann, P., Klamroth, R., Schutgens, R., Tangelder, M., Castaman, G., Schwäble, J., Bonig, H., et al. (2018) · Blood · doi:10.1182/blood-2017-09-804419 · Cited by 301
In vivo genome editing of the albumin locus as a platform for protein replacement therapy
Sharma, R., Anguela, X. M., Doyon, Y., Wechsler, T., DeKelver, R. C., Sproul, S., Paschon, D. E., Miller, J. C., Davidson, R. J., Shivak, D., et al. (2015) · Blood · doi:10.1182/blood-2014-12-615492 · Cited by 297
Self-citationGene therapy advances: A meta-analysis of AAV usage in clinical settings
Au, H. K. E., Isalan, M., & Mielcarek, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.809118 · Cited by 284
AAV cis -regulatory sequences are correlated with ocular toxicity
Xiong, W., Wu, D. M., Xue, Y., Wang, S. K., Chung, M. J., Ji, X., Rana, P., Zhao, S. R., Mai, S., & Cepko, C. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821000116 · Cited by 249
Meyer, K., Ferraiuolo, L., Schmelzer, L., Braun, L., McGovern, V., Likhite, S., Michels, O., Govoni, A., Fitzgerald, J., Morales, P., et al. (2015) · Molecular Therapy · doi:10.1038/mt.2014.210 · Cited by 286
McIntosh, J., Lenting, P. J., Rosales, C., Lee, D., Rabbanian, S., Raj, D., Patel, N., Tuddenham, E. G. D., Christophe, O. D., McVey, J. H., et al. (2013) · Blood · doi:10.1182/blood-2012-10-462200 · Cited by 278
Self-citationMeliani, 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
Self-citationCapsid modifications for targeting and improving the efficacy of AAV vectors
Büning, H., & Srivastava, A. (2019) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2019.01.008 · Cited by 260
Bucher, 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
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
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
Basic Biology of Adeno-Associated Virus (AAV) Vectors Used in Gene Therapy
Balakrishnan, B., & Jayandharan, G. (2014) · Current Gene Therapy · doi:10.2174/1566523214666140302193709 · Cited by 225
Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses
Chan, Y. K., Wang, S. K., Chu, C. J., Copland, D. A., Letizia, A. J., Costa Verdera, H., Chiang, J. J., Sethi, M., Wang, M. K., Neidermyer, W. J., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd3438 · Cited by 215
Self-citationGeorge, L. A., Ragni, M. V., Rasko, J. E. J., Raffini, L. J., Samelson-Jones, B. J., Ozelo, M., Hazbon, M., Runowski, A. R., Wellman, J. A., Wachtel, K., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.06.001 · Cited by 213
Self-citationWright, J. (2014) · Biomedicines · doi:10.3390/biomedicines2010080 · Cited by 219
Whole 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
Self-citationInfluence 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
Self-citationMingozzi, F., & High, K. A. (2017) · Annual Review of Virology · doi:10.1146/annurev-virology-101416-041936 · Cited by 206
Self-citationKonkle, 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
Gil-Farina, I., Fronza, R., Kaeppel, C., Lopez-Franco, E., Ferreira, V., D'Avola, D., Benito, A., Prieto, J., Petry, H., Gonzalez-Aseguinolaza, G., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.52 · Cited by 179
Childers, M. K., Joubert, R., Poulard, K., Moal, C., Grange, R. W., Doering, J. A., Lawlor, M. W., Rider, B. E., Jamet, T., Danièle, N., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007523 · Cited by 173
Adeno-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
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
Chicoine, L., Montgomery, C., Bremer, W., Shontz, K., Griffin, D., Heller, K., Lewis, S., Malik, V, Grose, W., Shilling, C., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2013.244 · Cited by 167
Mueller, C., Chulay, J. D., Trapnell, B. C., Humphries, M., Carey, B., Sandhaus, R. A., McElvaney, N. G., Messina, L., Tang, Q., Rouhani, F. N., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70314 · Cited by 169
Gao, K., Li, M., Zhong, L., Su, Q., Li, J., Li, S., He, R., Zhang, Y., Hendricks, G., Wang, J., et al. (2014) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2013.9 · Cited by 165
Addressing high dose AAV toxicity – ‘one and done’ or ‘slower and lower’
Kishimoto, T. K., & Samulski, R. J. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2060737 · Cited by 152
Martino, A. T., Basner-Tschakarjan, E., Markusic, D. M., Finn, J. D., Hinderer, C., Zhou, S., Ostrov, D. A., Srivastava, A., Ertl, H. C. J., Terhorst, C., et al. (2013) · Blood · doi:10.1182/blood-2012-10-460733 · Cited by 162
Self-citationPaulk, N. K., Pekrun, K., Zhu, E., Nygaard, S., Li, B., Xu, J., Chu, K., Leborgne, C., Dane, A. P., Haft, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.09.021 · Cited by 161
Self-citationLiver-directed lentiviral gene therapy in a dog model of hemophilia B
Cantore, A., Ranzani, M., Bartholomae, C. C., Volpin, M., Valle, P. D., Sanvito, F., Sergi, L. S., Gallina, P., Benedicenti, F., Bellinger, D., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa1405 · Cited by 158
Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer
Arjomandnejad, M., Dasgupta, I., Flotte, T. R., & Keeler, A. M. (2023) · BioDrugs · doi:10.1007/s40259-023-00585-7 · Cited by 159
Burnham, B., Nass, S., Kong, E., Mattingly, M., Woodcock, D., Song, A., Wadsworth, S., Cheng, S. H., Scaria, A., & O'Riordan, C. R. (2015) · Human Gene Therapy Methods · doi:10.1089/hgtb.2015.048 · Cited by 150
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
Rezvani, M., Español-Suñer, R., Malato, Y., Dumont, L., Grimm, A. A., Kienle, E., Bindman, J. G., Wiedtke, E., Hsu, B. Y., Naqvi, S. J., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.05.005 · Cited by 150
Universal Method for the Purification of Recombinant AAV Vectors of Differing Serotypes
Nass, S. A., Mattingly, M. A., Woodcock, D. A., Burnham, B. L., Ardinger, J. A., Osmond, S. E., Frederick, A. M., Scaria, A., Cheng, S. H., & O’Riordan, C. R. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.12.004 · Cited by 146
Pastore, N., Blomenkamp, K., Annunziata, F., Piccolo, P., Mithbaokar, P., Maria Sepe, R., Vetrini, F., Palmer, D., Ng, P., Polishchuk, E., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201202046 · Cited by 142
Annunziata, I., Patterson, A., Helton, D., Hu, H., Moshiach, S., Gomero, E., Nixon, R., & d’Azzo, A. (2013) · Nature Communications · doi:10.1038/ncomms3734 · Cited by 146
Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency
Prieve, M. G., Harvie, P., Monahan, S. D., Roy, D., Li, A. G., Blevins, T. L., Paschal, A. E., Waldheim, M., Bell, E. C., Galperin, A., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2017.12.024 · Cited by 145
Subacute Liver Failure Following Gene Replacement Therapy for Spinal Muscular Atrophy Type 1
Feldman, A. G., Parsons, J. A., Dutmer, C. M., Veerapandiyan, A., Hafberg, E., Maloney, N., & Mack, C. L. (2020) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2020.05.044 · Cited by 136
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
Priddy, F. H., Lewis, D. J. M., Gelderblom, H. C., Hassanin, H., Streatfield, C., LaBranche, C., Hare, J., Cox, J. H., Dally, L., Bendel, D., et al. (2019) · The Lancet HIV · doi:10.1016/s2352-3018(19)30003-7 · Cited by 131
Rogers, G. L., Shirley, J. L., Zolotukhin, I., Kumar, S. R. P., Sherman, A., Perrin, G. Q., Hoffman, B. E., Srivastava, A., Basner-Tschakarjan, E., Wallet, M. A., et al. (2017) · Blood · doi:10.1182/blood-2016-11-751040 · Cited by 131
Self-citationMeliani, 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
Self-citationNanoplatforms for mRNA Therapeutics
Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000099 · Cited by 130
Dyka, F. M., Boye, S. L., Chiodo, V. A., Hauswirth, W. W., & Boye, S. E. (2014) · Human Gene Therapy Methods · doi:10.1089/hgtb.2013.212 · Cited by 128
Adeno-Associated Virus (AAV) Versus Immune Response
Rabinowitz, J., Chan, Y. K., & Samulski, R. J. (2019) · Viruses · doi:10.3390/v11020102 · Cited by 122
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
Du, L. M., Nurden, P., Nurden, A. T., Nichols, T. C., Bellinger, D. A., Jensen, E. S., Haberichter, S. L., Merricks, E., Raymer, R. A., Fang, J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3773 · Cited by 119
Shao, W., Earley, L. F., Chai, Z., Chen, X., Sun, J., He, T., Deng, M., Hirsch, M. L., Ting, J., Samulski, R. J., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120474 · Cited by 119
Systemic AAV8-Mediated Gene Therapy Drives Whole-Body Correction of Myotubular Myopathy in Dogs
Mack, D. L., Poulard, K., Goddard, M. A., Latournerie, V., Snyder, J. M., Grange, R. W., Elverman, M. R., Denard, J., Veron, P., Buscara, L., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.02.004 · Cited by 114
Self-citationKlamroth, R., Hayes, G., Andreeva, T., Gregg, K., Suzuki, T., Mitha, I. H., Hardesty, B., Shima, M., Pollock, T., Slev, P., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2021.287 · Cited by 118
Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies
Markusic, D. M., Hoffman, B. E., Perrin, G. Q., Nayak, S., Wang, X., LoDuca, P. A., High, K. A., & Herzog, R. W. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201302859 · Cited by 116
Self-citationSuperior In vivo Transduction of Human Hepatocytes Using Engineered AAV3 Capsid
Vercauteren, K., Hoffman, B. E., Zolotukhin, I., Keeler, G. D., Xiao, J. W., Basner-Tschakarjan, E., High, K. A., Ertl, H. C., Rice, C. M., Srivastava, A., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.61 · Cited by 114
Self-citationHareendran, S., Balakrishnan, B., Sen, D., Kumar, S., Srivastava, A., & Jayandharan, G. R. (2013) · Reviews in Medical Virology · doi:10.1002/rmv.1762 · Cited by 113
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
Self-citationFischer, M. D., McClements, M. E., Martinez-Fernandez de la Camara, C., Bellingrath, J.-S., Dauletbekov, D., Ramsden, S. C., Hickey, D. G., Barnard, A. R., & MacLaren, R. E. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.05.005 · Cited by 112
Monahan, P. E., Sun, J., Gui, T., Hu, G., Hannah, W. B., Wichlan, D. G., Wu, Z., Grieger, J. C., Li, C., Suwanmanee, T., et al. (2015) · Human Gene Therapy · doi:10.1089/hum.2014.106 · Cited by 108
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
Self-citationZhao, H., Lee, K.-J., Daris, M., Lin, Y., Wolfe, T., Sheng, J., Plewa, C., Wang, S., & Meisen, W. H. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.06.004 · Cited by 98
Hyperfunctional coagulation factor IX improves the efficacy of gene therapy in hemophilic mice
Cantore, A., Nair, N., Della Valle, P., Di Matteo, M., Màtrai, J., Sanvito, F., Brombin, C., Di Serio, C., D'Angelo, A., Chuah, M., et al. (2012) · Blood · doi:10.1182/blood-2012-05-432591 · Cited by 101
Strategy to detect pre-existing immunity to AAV gene therapy
Falese, L., Sandza, K., Yates, B., Triffault, S., Gangar, S., Long, B., Tsuruda, L., Carter, B., Vettermann, C., Zoog, S. J., et al. (2017) · Gene Therapy · doi:10.1038/gt.2017.95 · Cited by 101
Immune 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
Li, C., Diprimio, N., Bowles, D. E., Hirsch, M. L., Monahan, P. E., Asokan, A., Rabinowitz, J., Agbandje-McKenna, M., & Samulski, R. J. (2012) · Journal of Virology · doi:10.1128/jvi.00675-12 · Cited by 96
Ayuso, E., Blouin, V., Lock, M., McGorray, S., Leon, X., Alvira, M. R., Auricchio, A., Bucher, S., Chtarto, A., Clark, K. R., et al. (2014) · Human Gene Therapy · doi:10.1089/hum.2014.057 · Cited by 94
Ertl, H. C. J., & High, K. A. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.172 · Cited by 94
Self-citationT Cell-Mediated Immune Responses to AAV and AAV Vectors
Ertl, H. C. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.666666 · Cited by 88
D'Costa, S., Blouin, V., Broucque, F., Penaud-Budloo, M., Fçranois, A., Perez, I. C., Le Bec, C., Moullier, P., Snyder, R. O., & Ayuso, E. (2016) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2016.19 · Cited by 89
Manufacturing of recombinant adeno-associated viruses using mammalian expression platforms
Robert, M., Chahal, P. S., Audy, A., Kamen, A., Gilbert, R., & Gaillet, B. (2017) · Biotechnology Journal · doi:10.1002/biot.201600193 · Cited by 89
Calcedo, R., Somanathan, S., Qin, Q., Betts, M. R., Rech, A. J., Vonderheide, R. H., Mueller, C., Flotte, T. R., & Wilson, J. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1617726114 · Cited by 79
Metadata
- Authors
- Nathwani, A. C., Tuddenham, E. G. D., Rangarajan, S., Rosales, C., McIntosh, J., Linch, D. C., Chowdary, P., Riddell, A., Pie, A. J., Harrington, C., O'Beirne, J., Smith, K., Pasi, J., Glader, B., Rustagi, P., Ng, C. Y. C., Kay, M. A., Zhou, J., Spence, Y., Morton, C. L., Allay, J., Coleman, J., Sleep, S., Cunningham, J. M., Srivastava, D., Basner-Tschakarjan, E., Mingozzi, F., High, K. A., Gray, J. T., Reiss, U. M., Nienhuis, A. W., & Davidoff, A. M.
- Affiliations
- NHS Blood and Transplant (GB)
- Basingstoke and North Hampshire Hospital (GB)
- University College London (GB)
- Queen Mary University of London (GB)
- Stanford Medicine (US)
- St. Jude Children's Research Hospital (US)
- University of Chicago (US)
- Children's Hospital of Philadelphia (US)
- ORCID
- Nathwani, Amit C.
- Tuddenham, Edward G.D.
- Rangarajan, Savita
- Rosales, Cecilia
- McIntosh, Jenny
- Linch, David C.
- Chowdary, Pratima
- Riddell, Anne
- Pasi, John
- Glader, Bertil
- Ng, Catherine Y.C.
- Kay, Mark A.
- Morton, Christopher L.
- Cunningham, John M.
- Mingozzi, Federico
- High, Katherine A.
- Gray, John T.
- Reiss, Ulrike M.
- Davidoff, Andrew M.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-12-22
- Volume
- 365
- Issue
- 25
- Pages
- 2357-2365
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3265081
- OpenAlex
- W2122304523
- Cited by
- 1,864
- References
- 27
- Citations by year
- 2026: 69 · 2025: 84 · 2024: 99 · 2023: 99 · 2022: 119 · 2021: 103 · 2020: 128 · 2019: 116 · 2018: 123 · 2017: 132 · 2016: 128 · 2015: 164 · 2014: 184 · 2013: 185 · 2012: 122
- FWCI
- 108.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Assisi Foundation of Memphis
- St. Jude Children's Research Hospital
- NHS Blood and Transplant
- American Lebanese Syrian Associated Charities
- National Institute for Health and Care Research (NF-SI-0507-10370, RP-PG-0310-1001)
- University College London
- Medical Research Council
- National Heart, Lung, and Blood Institute (HL094396, R01HL094396, R01HL073838, R01HL064274)
- Topics
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- 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
- Keywords
- hemophilia B, gene therapy, AAV8, factor IX, glucocorticoid therapy, aminotransferase elevation, bleeding phenotype, hepatocytes
- MeSH terms
- Dependovirus, Adult, Hemophilia B, Factor IX, Genetic Vectors, Humans, Infusions, Intravenous, Middle Aged, Genetic Therapy, 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
