Vector Uncoating Limits Adeno-Associated Viral Vector-Mediated Transduction of Human Dendritic Cells and Vector Immunogenicity
Open accessAbstract
AAV vectors poorly transduce Dendritic cells (DC), a feature invoked to explain AAV’s low immunogenicity. However, the reason for this non-permissiveness remained elusive. Here, we performed an in-depth analysis using human monocyte-derived immature DC (iDC) as model. iDC internalized AAV vectors of various serotypes, but even the most efficient serotype failed to transduce iDC above background. Since AAV vectors reached the cell nucleus, we hypothesized that AAV’s intracellular processing occurs suboptimal. On this basis, we screened an AAV peptide display library for capsid variants more suitable for DC transduction and identified the I/VSS family which transduced DC with efficiencies of up to 38%. This property correlated with an improved vector uncoating. To determine the consequence of this novel feature for AAV’s in vivo performance, we engineered one of the lead candidates to express a cytoplasmic form of ovalbumin, a highly immunogenic model antigen, and assayed transduction efficiency as well as immunogenicity. The capsid variant clearly outperformed the parental serotype in muscle transduction and in inducing antigen-specific humoral and T cell responses as well as anti-capsid CD8+ T cells. Hence, vector uncoating represents a major barrier hampering AAV vector-mediated transduction of DC and impacts on its use as vaccine platform.
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?
Viral particles can enter immune cells such as dendritic and microglial cells, though no transgene expression was observed.
“Recent studies have shown that while no transgene expression was observed, viral particles can enter the immune cells such as dendritic and microglial cells; though the question remains open as to whether they can reach the nucleus or whether their presence is only detected at the endoplasmic reticulum [92,93].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [92]
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
Merad, M., Sathe, P., Helft, J., Miller, J., & Mortha, A. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074950 · Cited by 2,309 · see citing works
Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002 · see citing works
Savina, A., Jancic, C. C., Hugues, S., Guermonprez, P., Vargas, P., Moura, I. C., Lennon‐Duménil, A., Seabra, M. C., Raposo, G., & Amigorena, S. (2006) · Cell · doi:10.1016/j.cell.2006.05.035 · Cited by 896 · 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
αVβ5 integrin: a co-receptor for adeno-associated virus type 2 infection
Summerford, C., Bartlett, J. S., & Samulski, R. J. (1999) · Nature Medicine · doi:10.1038/4768 · Cited by 711 · see citing works
The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy
Xie, Q., Bu, W., Bhatia, S., Hare, J., Somasundaram, T., Azzi, A., & Chapman, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162250899 · Cited by 612 · see citing works
Phagocytosis and antigen presentation in dendritic cells
Savina, A., & Amigorena, S. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00552.x · Cited by 562 · see citing works
Production and purification of serotype 1, 2, and 5 recombinant adeno-associated viral vectors
Zolotukhin, S., Potter, M., Zolotukhin, I., Sakai, Y., Loiler, S., Fraites, T. J., Chiodo, V. A., Philipsberg, T., Muzyczka, N., Hauswirth, W. W., et al. (2002) · Methods · doi:10.1016/s1046-2023(02)00220-7 · Cited by 556 · see citing works
Jooss, K., Yang, Y., Fisher, K. J., & Wilson, J. M. (1998) · Journal of Virology · doi:10.1128/jvi.72.5.4212-4223.1998 · Cited by 470 · see citing works
Dalod, M., Chelbi, R., MALISSEN, B., & Lawrence, T. (2014) · The EMBO Journal · doi:10.1002/embj.201488027 · Cited by 430 · see citing works
Identification of a heparin-binding motif on adeno-associated virus type 2 capsids
Kern, A., Schmidt, K., Leder, C., Müller, O. J., Wobus, C. E., Bettinger, K., Von der Lieth, C. W., King, J. A., & Kleinschmidt, J. A. (2003) · Journal of Virology · doi:10.1128/jvi.77.20.11072-11081.2003 · Cited by 380 · see citing works
Opie, S. R., Warrington, Agbandje-McKenna, M., Zolotukhin, S., & Muzyczka, N. (2003) · Journal of Virology · doi:10.1128/jvi.77.12.6995-7006.2003 · Cited by 364 · 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
Girod, A., Wobus, C. E., Zádori, Z., Ried, M., Leike, K., Tijssen, P., Kleinschmidt, J. A., & Hallek, M. (2002) · Journal of General Virology · doi:10.1099/0022-1317-83-5-973 · Cited by 354 · see citing works
Self-citationZhu, J., Huang, X., & Yang, Y. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37607 · Cited by 330 · see citing works
Langlet, C., Tamoutounour, S., Henri, S., Luche, H., Ardouin, L., Grégoire, C., MALISSEN, B., & Guilliams, M. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102744 · Cited by 284 · see citing works
Sonntag, F., Bleker, S., Leuchs, B., Fischer, R., & Kleinschmidt, J. A. (2006) · Journal of Virology · doi:10.1128/jvi.01056-06 · Cited by 277 · see citing works
Genetic Fate of Recombinant Adeno-Associated Virus Vector Genomes in Muscle
Schnepp, B. C., Clark, K. R., Klemanski, D. L., Pacak, C. A., & Johnson, P. R. (2003) · Journal of Virology · doi:10.1128/jvi.77.6.3495-3504.2003 · Cited by 262 · see citing works
Intracellular transport of recombinant adeno-associated virus vectors
Nonnenmacher, M., & Weber, T. (2012) · Gene Therapy · doi:10.1038/gt.2012.6 · Cited by 258 · see citing works
Dendritic cell maturation and cross‐presentation: timing matters!
Alloatti, A., Kotsias, F., Magalhaes, J. G., & Amigorena, S. (2016) · Immunological Reviews · doi:10.1111/imr.12432 · Cited by 244 · see citing works
Factors Influencing Recombinant Adeno-Associated Virus Production
Salvetti, A., Orève, S., Chadeuf, G., Favre, D., Chérel, Y., Champion-Arnaud, P., David-Ameline, J., & Moullier, P. (1998) · Human Gene Therapy · doi:10.1089/hum.1998.9.5-695 · Cited by 241 · see citing works
Self-citationIn vitro selection of viral vectors with modified tropism: the adeno-associated virus display
Perabò, L., Büning, H., Kofler, D. M., Ried, M. U., Girod, A., Wendtner, C., Enssle, J., & Hallek, M. J. (2003) · Molecular Therapy · doi:10.1016/s1525-0016(03)00123-0 · Cited by 232 · see citing works
Self-citationStructural insight into the unique properties of adeno-associated virus serotype 9
DiMattia, M. A., Nam, H.-J., Van Vliet, K., Mitchell, M., Bennett, A., Gurda, B. L., McKenna, R., Olson, N. H., Sinkovits, R. S., Potter, M., et al. (2012) · Journal of Virology · doi:10.1128/jvi.07232-11 · Cited by 219 · see citing works
Efficient and Selective AAV2-Mediated Gene Transfer Directed to Human Vascular Endothelial Cells
Nicklin, S. A., Buening, H., Dishart, K. L., de Alwis, M., Girod, A., Hacker, U., Thrasher, A. J., Ali, R. R., Hallek, M. J., & Baker, A. H. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0424 · Cited by 219 · see citing works
Self-citationSubcellular compartmentalization of adeno-associated virus type 2 assembly
Wistuba, A., Kern, A., Weger, S., Grimm, D., & Kleinschmidt, J. A. (1997) · Journal of Virology · doi:10.1128/jvi.71.2.1341-1352.1997 · Cited by 219 · see citing works
Structurally mapping the diverse phenotype of adeno-associated virus serotype 4
Govindasamy, L., Padron, E., McKenna, R., Muzyczka, N., Kaludov, N., Chiorini, J. A., & Agbandje-McKenna, M. (2006) · Journal of Virology · doi:10.1128/jvi.01536-06 · Cited by 205 · see citing works
Adeno-Associated Virus 2 Infection Requires Endocytosis through the CLIC/GEEC Pathway
Nonnenmacher, M. E., & Weber, T. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.10.014 · Cited by 199 · see citing works
Greber, U. F. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8453-3 · Cited by 186 · see citing works
Nuclear Targeting of Macromolecular Polyanions by an HIV-Tat Derived Peptide
Sandgren, S., Cheng, F., & Belting, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205395200 · Cited by 174 · see citing works
Structural Characterization of the Dual Glycan Binding Adeno-Associated Virus Serotype 6
Ng, R., Lakshmanan Govindasamy, A., Gurda, B. L., McKENNA, R. V., Kozyreva, O. G., Samulski, R. J., Parent, K. N., Baker, T. S., & Agbandje‐McKenna, M. (2010) · Journal of Virology · doi:10.1128/jvi.01235-10 · Cited by 143 · see citing works
Horowitz, E. D., Rahman, K. S., Bower, B. D., Dismuke, D. J., Falvo, M. R., Griffith, J. D., Harvey, S. C., & Asokan, A. (2013) · Journal of Virology · doi:10.1128/jvi.03017-12 · Cited by 139 · see citing works
Perabò, L., Goldnau, D., White, K., Endell, J., Bouças, J., Humme, S., Work, L. M., Janicki, H., Hallek, M. J., Baker, A. H., et al. (2006) · Journal of Virology · doi:10.1128/jvi.00076-06 · Cited by 135 · see citing works
Self-citationTseng, Y.-S., & Agbandje‐McKenna, M. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00009 · Cited by 134 · 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
Capsid antibodies to different adeno-associated virus serotypes bind common regions
Gurda, B. L., DiMattia, M. A., Miller, E. B., Bennett, A., McKenna, R., Weichert, W. S., Nelson, C. D., Chen, W.-J., Muzyczka, N., Olson, N. H., et al. (2013) · Journal of Virology · doi:10.1128/jvi.00622-13 · Cited by 127 · see citing works
Stahnke, S., Lux, K., Uhrig, S., Kreppel, F., Hösel, M., Coutelle, O., Ogris, M., Hallek, M. J., & Büning, H. (2010) · Virology · doi:10.1016/j.virol.2010.09.025 · Cited by 126 · see citing works
Self-citationAdeno-associated virus-2 and its primary cellular receptor—Cryo-EM structure of a heparin complex
O’Donnell, J., Taylor, K. A., & Chapman, M. S. (2009) · Virology · doi:10.1016/j.virol.2008.11.037 · Cited by 126 · see citing works
The Varieties of Immunological Experience: Of Pathogens, Stress, and Dendritic Cells
Pulendran, B. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-075049 · Cited by 120 · see citing works
Engineering the AAV capsid to optimize vector–host-interactions
Büning, H., Huber, A., Zhang, L. N., Meumann, N., & Hacker, U. T. (2015) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2015.08.002 · Cited by 113 · see citing works
Self-citationHeparin binding induces conformational changes in Adeno-associated virus serotype 2
Levy, H. C., Bowman, V. D., Govindasamy, L., McKenna, R., Nash, K., Warrington, K., Chen, W., Muzyczka, N., Yan, X., Baker, T. S., et al. (2009) · Journal of Structural Biology · doi:10.1016/j.jsb.2008.12.002 · Cited by 110 · see citing works
Popa-Wagner, R., Porwal, M., Kann, M., Reuss, M., Weimer, M., Florin, L., & Kleinschmidt, J. A. (2012) · Journal of Virology · doi:10.1128/jvi.00282-12 · Cited by 109 · see citing works
Nam, H.-J., Gurda, B. L., McKenna, R., Potter, M., Byrne, B., Salganik, M., Muzyczka, N., & Agbandje-McKenna, M. (2011) · Journal of Virology · doi:10.1128/jvi.05305-11 · Cited by 108 · see citing works
Heparan sulfate in the nucleus and its control of cellular functions
Stewart, M. D., & Sanderson, R. D. (2013) · Matrix Biology · doi:10.1016/j.matbio.2013.10.009 · Cited by 106 · see citing works
AAV Vectors Vaccines Against Infectious Diseases
Nieto, K., & Salvetti, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00005 · Cited by 100 · see citing works
Self-citationMapping a Neutralizing Epitope onto the Capsid of Adeno-Associated Virus Serotype 8
Gurda, B. L., Raupp, C., Popa-Wagner, R., Naumer, M., Olson, N. H., Ng, R., McKENNA, R. V., Baker, T. S., Kleinschmidt, J. A., & Agbandje‐McKenna, M. (2012) · Journal of Virology · doi:10.1128/jvi.00218-12 · Cited by 93 · see citing works
Dendritic Cells Continue To Capture and Present Antigens after Maturation In Vivo
Drutman, S. B., & Trombetta, E. S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000642 · Cited by 92 · see citing works
Adeno-associated Virus as a Mammalian DNA Vector
Salganik, M., Hirsch, M. L., & Samulski, R. J. (2015) · Microbiology Spectrum · doi:10.1128/microbiolspec.mdna3-0052-2014 · Cited by 88 · see citing works
Characterization of AAV vector particle stability at the single-capsid level
Bernaud, J., Rossi, A., Fis, A., Gardette, L., Aillot, L., Büning, H., Castelnovo, M., Salvetti, A., & Faivre-Moskalenko, C. (2018) · Journal of Biological Physics · doi:10.1007/s10867-018-9488-5 · Cited by 83 · see citing works
Self-citationWegrowski, Y., Milard, A.-L., Kotlarz, G., Toulmonde, E., Maquart, F.-X., & Bernard, J. (2006) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2006.03059.x · Cited by 70 · see citing works
Detection of HBV Covalently Closed Circular DNA
Li, X., Zhao, J., Yuan, Q., & Xia, N. (2017) · Viruses · doi:10.3390/v9060139 · Cited by 60 · see citing works
Schinnerling, K., García-González, P. A., & Aguillón, J. C. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00528 · Cited by 56 · see citing works
Pandya, J., Ortiz, L., Ling, C., Rivers, A. E., & Aslanidi, G. (2013) · Immunology and Cell Biology · doi:10.1038/icb.2013.74 · Cited by 55 · see citing works
Alazard-Dany, N., Nicolas, A., Ploquin, A., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000340 · Cited by 55 · see citing works
Uhrig, S., Coutelle, O., Wiehe, T., Perabò, L., Hallek, M. J., & Büning, H. (2011) · Gene Therapy · doi:10.1038/gt.2011.78 · Cited by 53 · see citing works
Self-citationFrançois, A., Bouzelha, M., Lecomte, E., Broucque, F., Penaud-Budloo, M., Adjali, O., Moullier, P., Blouin, V., & Ayuso, E. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2018.07.004 · Cited by 50 · see citing works
Tropism-modified AAV Vectors Overcome Barriers to Successful Cutaneous Therapy
Sallach, J., Pasquale, G. D., Larcher, F., Niehoff, N., Rübsam, M., Huber, A., Chiorini, J., Almarza, D., Eming, S. A., Ulus, H., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.14 · Cited by 47 · see citing works
Self-citationHotta, C., Fujimaki, H., Yoshinari, M., Nakazawa, M., & Minami, M. (2005) · Immunology · doi:10.1111/j.1365-2567.2005.02270.x · Cited by 47 · see citing works
Dendritic cells—At the front-line of pathogen attack
McCullough, K. C., Ruggli, N., & Summerfield, A. (2008) · Veterinary Immunology and Immunopathology · doi:10.1016/j.vetimm.2008.10.290 · Cited by 43 · see citing works
Viral mechanisms for docking and delivering at nuclear pore complexes
Flatt, J. W., & Greber, U. F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.05.008 · Cited by 36 · see citing works
Adriouch, S., Franck, E., Drouot, L., Bonneau, C., Jolinon, N., Salvetti, A., & Boyer, O. (2011) · Frontiers in Microbiology · doi:10.3389/fmicb.2011.00199 · Cited by 23 · see citing works
Self-citationHardet, R., Chevalier, B., Dupaty, L., Naïmi, Y., Riou, G., Drouot, L., Jean, L., Salvetti, A., Boyer, O., & Adriouch, S. (2015) · Molecular Therapy · doi:10.1038/mt.2015.146 · Cited by 20 · see citing works
Self-citationAutenrieth, S. E., Grimm, S., Rittig, S. M., Grünebach, F., Gouttefangeas, C., & Bühring, H. (2015) · Clinical & Translational Immunology · doi:10.1038/cti.2015.29 · Cited by 18 · see citing works
Ghenassia, A., Gross, D., Lorain, S., Tros, F., Urbain, D., Benkhelifa‐Ziyyat, S., Charbit, A., Davoust, J. M., & Chappert, P. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.06.019 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
AAV 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
Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders
Pavlou, M., Schön, C., Occelli, L. M., Rossi, A., Meumann, N., Boyd, R. F., Bartoe, J. T., Siedlecki, J., Gerhardt, M. J., Babutzka, S., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013392 · Cited by 135 · see citing works
Self-citationJourney to the Center of the Cell: Tracing the Path of AAV Transduction
Dhungel, B. P., Bailey, C. G., & Rasko, J. E. J. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2020.09.010 · Cited by 122 · see citing works
Westhaus, A., Cabanes-Creus, M., Rybicki, A., Baltazar, G., Navarro, R. G., Zhu, E., Drouyer, M., Knight, M., Albu, R. F., Ng, B. H., et al. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.264 · Cited by 102 · see citing works
Humoral immune responses to <scp>AAV</scp> gene therapy in the ocular compartment
Whitehead, M., Osborne, A., Yu‐Wai‐Man, P., & Martin, K. (2021) · Biological Reviews · doi:10.1111/brv.12718 · Cited by 52 · see citing works
Rode, L., Bär, C., Groß, S., Rossi, A., Meumann, N., Viereck, J., Abbas, N., Xiao, K., Riedel, I., Gietz, A., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.07.003 · Cited by 48 · see citing works
Self-citationModifying immune responses to adeno-associated virus vectors by capsid engineering
Bentler, M., Hardet, R., Ertelt, M., Rudolf, D., Kaniowska, D., Schneider, A., Vondran, F. W. R., Schoeder, C. T., Delphin, M., Lucifora, J., et al. (2023) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2023.08.015 · Cited by 34 · see citing works
Self-citationRisk mitigation of immunogenicity: a key to personalized retinal gene therapy
Varin, J., Morival, C., Maillard, N., Adjali, O., & Cronin, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312818 · Cited by 19 · see citing works
- Authors
- Rossi, A., Dupaty, L., Aillot, L., Zhang, L., Gallien, C., Hallek, M., Odenthal, M., Adriouch, S., Salvetti, A., & Büning, H.
- Affiliations
- Lyon 1 Université (FR)
- Inserm (FR)
- University of Cologne (DE)
- University Hospital Cologne (DE)
- Corresponding author
- Adriouch, Sahil
- Salvetti, Anna
- Büning, Hildegard
- ORCID
- Venue
- Scientific Reports
- Published
- 2019-03-06
- Volume
- 9
- Issue
- 1
- Pages
- 3631-3631
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6403382
- OpenAlex
- W2918328056
- Cited by
- 85
- References
- 63
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 8 · 2022: 15 · 2021: 15 · 2020: 13 · 2019: 5
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- HAL (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- PhD program from La Region Rhone-Alpes
- Association Fran&#x00E7;aise contre les Myopathies (#21354, #18030, #14806)
- University of Cologne
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- adeno-associated virus vectors, dendritic cells, AAV serotypes, monocyte-derived dendritic cells, dendritic cell transduction, vector immunogenicity, ovalbumin, vaccine platforms
- MeSH terms
- Dependovirus, Animals, Capsid, Dendritic Cells, Genetic Vectors, Humans, Male, Mice, Inbred C57BL, Transduction, Genetic, CD8-Positive T-Lymphocytes, Capsid Proteins, 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
