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.).
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?
Pre-existing antibodies correlated with decreased efficacy of gene therapy in clinical trials where administration exposes vector to serum.
“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]
The Results section (Safety and Efficacy of Peripheral-Vein Infusion of Vector; page unavailable) reports that Participant 3 had higher pre-treatment anti-AAV8 antibody levels and initially low FIX activity, raising the possibility that antibodies blocked transduction. It does not establish a correlation across clinical trials: the authors describe one participant, and his later FIX levels were consistent with successful transgene expression. (LLM, conf=0.84)
Experimental — accuracy not yet measuredNABs are often the most commonly invoked exclusion criterion for patient enrollment.
“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]
The Methods > Study Design passage says that patients enrolled in this hemophilia B trial had to lack neutralizing antibodies to AAV8, supporting their use as an enrollment exclusion criterion. It does not establish that this criterion is often used or is the most commonly invoked across trials. No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLiver-directed AAV treatments can raise liver transaminases alongside reduced FIX expression, probably because capsid-specific cytotoxic T cells destroy transduced hepatocytes.
“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]
AAV clinical successes to date have involved delivery either to immune privileged regions or to subjects lacking apparent AAV immunological memory.
“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]
Certain host responses have only been observed with very high doses of intravenous AAV, suggesting a threshold effect for these host reactions.
“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]
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.
“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]
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.
“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]
Antibody formation against capsid was also not impacted by CpG depletion in clinical trials.
“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]
Immunosuppression is required to maintain transgene expression in patients treated with AAVs.
“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]
CCS are used short-term in conjunction with systemically delivered gene therapies to negate transaminitis and associated CTL-induced injury transgene loss.
“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.
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 · 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
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 · see citing works
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 · see citing works
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 · 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
Self-citationSawa, 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 552 · see citing works
Darby, 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 · see citing works
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 421 · see citing works
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 · see citing works
Self-citationMuscular exercise can cause highly pathological liver function tests in healthy men
Pettersson, J., Hindorf, U., Persson, P., Bengtsson, T., Malmqvist, U. P., Werkström, V., & Ekelund, M. (2007) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2007.03001.x · Cited by 357 · see citing works
Nathwani, A. C., Rosales, C., McIntosh, J., Rastegarlari, G., Nathwani, D., Raj, D., Nawathe, S., Waddington, S. N., Bronson, R., Jackson, S., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2010.274 · Cited by 345 · see citing works
Self-citationBrantly, M. L., Chulay, J. D., Wang, L., Mueller, C., Humphries, M., Spencer, L. T., Rouhani, F., Conlon, T. J., Calcedo, R., Betts, M. R., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904514106 · Cited by 327 · see citing works
Mingozzi, 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-citationNathwani, A. C., Gray, J. T., McIntosh, J., Ng, C. Y., Zhou, J., Spence, Y., Cochrane, M., Gray, E., Tuddenham, E. G. D., & Davidoff, A. M. (2006) · Blood · doi:10.1182/blood-2006-03-010181 · Cited by 272 · see citing works
Self-citationDEN UIJL, I. E. M., FISCHER, K., VAN DER BOM, J. G., GROBBEE, D. E., ROSENDAAL, F. R., & PLUG, I. (2011) · Haemophilia · doi:10.1111/j.1365-2516.2010.02383.x · Cited by 214 · see citing works
Allay, J. A., Sleep, S., Long, S., Tillman, D. M., Clark, R., Carney, G., Fagone, P., McIntosh, J. H., Nienhuis, A. W., Davidoff, A. M., et al. (2011) · Human Gene Therapy · doi:10.1089/hum.2010.202 · Cited by 152 · see citing works
Self-citationSmith, J. E., Garbutt, G., Lopes, P., & Pedoe, D. T. (2004) · British Journal of Sports Medicine · doi:10.1136/bjsm.2002.002873 · Cited by 131 · see citing works
Fagone, P., Wright, J. F., Nathwani, A. C., Nienhuis, A. W., Davidoff, A. M., & Gray, J. T. (2012) · Human Gene Therapy Methods · doi:10.1089/hgtb.2011.104 · Cited by 97 · see citing works
Self-citationCellular immune response to cryptic epitopes during therapeutic gene transfer
Li, C., Goudy, K., Hirsch, M., Asokan, A., Fan, Y., Alexander, J., Sun, J., Monahan, P., Seiber, D., Sidney, J., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902269106 · Cited by 79 · see citing works
Epidemiology of coagulation disorders
Nathwani, A. C., & Tuddenham, E. G. D. (1992) · Baillière s Clinical Haematology · doi:10.1016/s0950-3536(11)80025-9 · Cited by 67 · see citing works
Self-citationProspects for gene therapy of haemophilia
Nathwani, A., Davidoff, A., & Tuddenham, E. (2004) · Haemophilia · doi:10.1111/j.1365-2516.2004.00926.x · Cited by 60 · see citing works
Self-citationMeasurement of Mild Factor VIII Inhibitors in Bethesda Units
Kasper, C. K., & Pool, J. G. (1975) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1651380 · Cited by 55 · see citing works
Coiffier, B., Pro, B., Prince, H., Foss, F., Sokol, L., Greenwood, M., Caballero, D., Borchmann, P., Morschhauser, F., Wilhelm, M., et al. (2010) · Blood · doi:10.1182/blood.v116.21.114.114 · Cited by 49 · see citing works
Letter: Measurement of mild factor VIII inhibitors in Bethesda units.
Ck, K., & Jg, P. (1975) · PubMed · Cited by 34 · see citing works
Nathwani, A., Tuddenham, E., Rosales, C., McIntosh, J., Riddell, A., Rustagi, P., Glader, B., Kay, M., Allay, J. A., Coleman, J., et al. (2010) · Blood · doi:10.1182/blood.v116.21.248.248 · Cited by 24 · see citing works
Self-citationManno, C. S., Arruda, V. R., Pierce, G. F., et al. (2006) · Nature Medicine · doi:10.1038/nm0506-592b · Cited by 11 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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-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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationCurrent 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 · see citing works
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 · 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-citationHigh, K. A., & Roncarolo, M. G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1706910 · Cited by 555 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
Immunogenicity and toxicity of AAV gene therapy
Ertl, H. C. J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.975803 · Cited by 402 · see citing works
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 · 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-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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Keeler, A. M., & Flotte, T. R. (2019) · Annual Review of Virology · doi:10.1146/annurev-virology-092818-015530 · Cited by 322 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
AAV <i>cis</i> -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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
Self-citationWright, J. (2014) · Biomedicines · doi:10.3390/biomedicines2010080 · Cited by 219 · 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-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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Adeno-Associated Virus (AAV) Versus Immune Response
Rabinowitz, J., Chan, Y. K., & Samulski, R. J. (2019) · Viruses · doi:10.3390/v11020102 · Cited by 122 · 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
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · 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-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 · see citing works
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 · 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-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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Ertl, H. C. J., & High, K. A. (2017) · Human Gene Therapy · doi:10.1089/hum.2016.172 · Cited by 94 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Rogers, G. L., Suzuki, M., Zolotukhin, I., Markusic, D. M., Morel, L. M., Lee, B., Ertl, H. C. J., & Herzog, R. W. (2015) · Journal of Innate Immunity · doi:10.1159/000369273 · Cited by 85 · see citing works
- 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
