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Identification of preexisting adaptive immunity to Cas9 proteins in humans
Open accessPublished version of a preprint
Abstract
The CRISPR-Cas9 system is a powerful tool for genome editing, which allows the precise modification of specific DNA sequences. Many efforts are underway to use the CRISPR-Cas9 system to therapeutically correct human genetic diseases 1-6. The most widely used orthologs of Cas9 are derived from Staphylococcus aureus and Streptococcus pyogenes 5,7. Given that these two bacterial species infect the human population at high frequencies 8,9, we hypothesized that humans may harbor preexisting adaptive immune responses to the Cas9 orthologs derived from these bacterial species, SaCas9 (S. aureus) and SpCas9 (S. pyogenes). By probing human serum for the presence of anti-Cas9 antibodies using an enzyme-linked immunosorbent assay, we detected antibodies against both SaCas9 and SpCas9 in 78% and 58% of donors, respectively. We also found anti-SaCas9 T cells in 78% and anti-SpCas9 T cells in 67% of donors, which demonstrates a high prevalence of antigen-specific T cells against both orthologs. We confirmed that these T cells were Cas9-specific by demonstrating a Cas9-specific cytokine response following isolation, expansion, and antigen restimulation. Together, these data demonstrate that there are preexisting humoral and cell-mediated adaptive immune responses to Cas9 in humans, a finding that should be taken into account as the CRISPR-Cas9 system moves toward clinical trials.
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In the citing paper
“Second, long-term expression of genome editing molecules may expose patients to undesired off-target editing or immune reactions 66,67 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [66]
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
“Pre-existing Cas9 antibodies and reactive T-cells have been detected in humans exposed to pathogenic bacteria harboring CRISPR systems, although it is unknown whether these are present at concentrations sufficient to trigger an immune response to the genome editing enzymes 66,104 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [66]
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
“although it is unknown whether these are present at concentrations sufficient to trigger an immune response to the genome editing enzymes 66,104 .”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [66]
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
“Other factors affecting clinical applications of genome editing include the immunogenicity of bacterially-derived editing proteins, the potential for pre-existing antibodies against CRISPR components to cause inflammation and the unknown long-term safety and stability of genome editing outcomes.”
From The promise and challenge of therapeutic genome editing (2020) · cites this paper as [66]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Another consideration for CRISPR/Cas9-based systems for retinal gene editing is the potential for a heightened adaptive immune response given the bacterial origin of the Cas9 enzyme and high prevalence of pre-existing immunity (Charlesworth et al., 2019).”
From Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy (2025) · cites this paper as Charlesworth et al., 2019
In the citing paper
“A study involving 125 healthy adult human blood donors in the USA with a median age of 43 reported pre-existing anti-SaCas9 antibodies and anti-SpCas9 antibodies in 78% and 58% of the total samples, respectively.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [24]
In the citing paper
“Among the tested donors, 78% had SaCas9-specific T-cells and 67% were positive for SpCas9-specific T-cells.”
From Immune responses to gene editing by viral and non-viral delivery vectors used in retinal gene therapy (2022) · cites this paper as [24]
In the citing paper
“While there are discrepancies regarding the exact prevalence of these antibodies in humans, a majority of the general population may exhibit preexisting α-Cas93.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [3]
In the citing paper
“Furthermore, a high prevalence of preexisting cellular immunity against Cas9 (Cas9-reactive T-cells) has also been identified2–4.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [3]
In the citing paper
“multiple groups have reported high frequencies (>60% of patients) of Cas9 reactive T-cells in humans2–4.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [3]
In the citing paper
“This may explain the lower raw ELISA A450 values we observed compared with previous work (Table 1)3.”
From Investigation of Cas9 Antibodies in the Human Eye (2022) · cites this paper as [3]
In the citing paper
“CRISPR-Cas9 is a promising therapeutic tool that allows genetic target-specific cleavage and editing (111).”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [111]
In the citing paper
“One concern is that the prevalence of anti-SaCas9 antibodies and T-cell in humans are reported to be 78% (111).”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [111]
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Citations
Cites
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. (2012) · Science · doi:10.1126/science.1225829 · Cited by 17,116
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Staphylococcus aureus Infections
Lowy, F. D. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808203390806 · Cited by 6,018
In vivo genome editing using Staphylococcus aureus Cas9
Ran, F. A., Cong, L., Yan, W. X., Scott, D. A., Gootenberg, J. S., Kriz, A. J., Zetsche, B., Shalem, O., Wu, X., Makarova, K. S., et al. (2015) · Nature · doi:10.1038/nature14299 · Cited by 2,687
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
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
Eyquem, J., Mansilla-Soto, J., Giavridis, T., van der Stegen, S. J. C., Hamieh, M., Cunanan, K. M., Odak, A., Gönen, M., & Sadelain, M. (2017) · Nature · doi:10.1038/nature21405 · Cited by 1,831
Zuris, J. A., Thompson, D. B., Shu, Y., Guilinger, J. P., Bessen, J. L., Hu, J. H., Maeder, M. L., Joung, J. K., Chen, Z.-Y., & Liu, D. R. (2015) · Nature Biotechnology · doi:10.1038/nbt.3081 · Cited by 1,460
In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration
Suzuki, K., Tsunekawa, Y., Hernandez-Benitez, R., Wu, J., Zhu, J., Kim, E. J., Hatanaka, F., Yamamoto, M., Araoka, T., Li, Z., et al. (2016) · Nature · doi:10.1038/nature20565 · Cited by 1,150
In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy
Nelson, C. E., Hakim, C. H., Ousterout, D. G., Thakore, P. I., Moreb, E. A., Rivera, R. M. C., Madhavan, S., Pan, X., Ran, F. A., Yan, W. X., et al. (2016) · Science · doi:10.1126/science.aad5143 · Cited by 1,144
Pukelsheim, F. (1994) · The American Statistician · doi:10.1080/00031305.1994.10476030 · Cited by 1,072
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Riley, J. S., Luks, V. L., Berkowitz, C. L., Dumitru, A. M., Kus, N. J., Dave, A., Menon, P. V., Paepe, M. E. D., Jain, R., Li, L., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci179848 · Cited by 5
Tong, L.-W., Hu, Y.-S., Yu, S.-J., Li, C., & Shao, J. (2024) · Nanotechnology · doi:10.1088/1361-6528/ad5f33 · Cited by 5
CircRNA-based therapeutics: Current opinions and clinical potential
Liu, H., Yao, X., Zhou, Y. L., & Chen, L. (2024) · The Innovation Medicine · doi:10.59717/j.xinn-med.2024.100081 · Cited by 5
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Raali, R., & Suresh, P. K. (2024) · Current Gene Therapy · doi:10.2174/0115665232351747241113050243 · Cited by 5
CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer
Noruzi, S., Mohammadi, R., & Jamialahmadi, K. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03480-2 · Cited by 5
David, M., Schiele, P., Monteferrario, D., Saviane, G., Martelli, A. E., Dupont, C. F., Jeanneau, C., Marchetti, I., Tadi, S. K., Vahldick, J., et al. (2025) · Molecular Therapy Oncology · doi:10.1016/j.omton.2025.200989 · Cited by 5
Early postnatal expression mitigates immune responses to Cas9 in the murine central nervous system
Duba-Kiss, R., & Hampson, D. R. (2025) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2025.101536 · Cited by 5
Smith, T. S., Singh, P., Bhana, R., Kairuz, D., Bloom, K. M., Maepa, M. B., Ely, A., & Arbuthnot, P. B. (2025) · Viruses · doi:10.3390/v17081090 · Cited by 5
Viral delivery of genome-modifying proteins for cellular reprogramming
Mikkelsen, J. G. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.06.005 · Cited by 6
Lung stem cells and therapy for cystic fibrosis
Vaidyanathan, S., McCarra, M. B., & Desai, T. (2021) · European Respiratory Society eBooks · doi:10.1183/2312508x.10010520 · Cited by 5
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Croze, R. H., Kotterman, M. A., Burns, C. H., Schmitt, C. E., Quezada, M., Schaffer, D. V., Kirn, D. H., & Francis, P. J. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000361 · Cited by 5
Prenatal Gene Therapy for Metabolic Disorders
Coons, B. E., & Peranteau, W. H. (2021) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0000000000000662 · Cited by 5
Simhadri, V. L., McGill, J. R., & Sauna, Z. E. (2021) · Gene Therapy · doi:10.1038/s41434-021-00301-6 · Cited by 5
Pfromm, J. K., Bonillo, M., Dauletbekov, D., Bucher, K., & Fischer, M. D. (2022) · Scientific Reports · doi:10.1038/s41598-022-17269-x · Cited by 5
Armstrong, D. A., Hudson, T. R., Hodge, C. A., Hampton, T. H., Howell, A. L., & Hayden, M. S. (2023) · RNA Biology · doi:10.1080/15476286.2023.2221510 · Cited by 5
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Ates, I., Stuart, C., Rathbone, T., Barzi, M., He, G., Major, A. M., Shankar, V., Lyman, R. A., Angner, S. S., Mackay, T. F. C., et al. (2024) · Hepatology Communications · doi:10.1097/hc9.0000000000000424 · Cited by 5
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Shams, F., Sharif, E., Abbasi‐Kenarsari, H., Hashemi, N., Hosseini, M. S., Heidari, N., Noori, E., Amini, A. H., Bazrgar, M., Rouhani, M., et al. (2025) · Current Gene Therapy · doi:10.2174/0115665232357078250331180413 · Cited by 6
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Lucibello, F., Menegatti, S., & Menger, L. (2019) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2019.05.048 · Cited by 5
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Tsanov, M. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.11.012 · Cited by 5
Applications of genome editing in farm animals
Kumar, D., & Kues, W. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816352-8.00005-9 · Cited by 5
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Lymberi, P., Ζαννίκου, Μ., & Hatzioannou, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00197-3 · Cited by 5
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Zhang, C. C. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.10.025 · Cited by 4
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Xue, J., & Yao, Z. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.09.008 · Cited by 5
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Hussen, B. M., Ismael, B. S., Abdulla, S. S., Jamal, N. H., Mustafa, S. A., Najmalddin, Z. B., & Rasul, M. F. (2024) · BioMed Target Journal · doi:10.59786/bmtj.221 · Cited by 4
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Leal, A. F., Prieto, L. E., & Pachajoa, H. (2025) · Cells · doi:10.3390/cells14151147 · Cited by 4
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Janetzki, Z. T., McCoullough, L. C., Revill, P. A., & Littlejohn, M. (2026) · Antiviral Research · doi:10.1016/j.antiviral.2026.106355 · Cited by 4
Mallol-Simmonds, M., Avila, C., Cañete, I., Parra-Lucares, A., Pena-Silva, J., & Bustamante, S. (2026) · Biomedicines · doi:10.3390/biomedicines14020486 · Cited by 4
Dai, Y., Abudujielili, Z., Ding, Y., Huang, W., Yin, J., Ou, L., Hu, J., Zheng, S., & Li, C. (2026) · Science Advances · doi:10.1126/sciadv.aea8052 · Cited by 4
Mengistu, G. (2026) · The Journal of Gene Medicine · doi:10.1002/jgm.70091 · Cited by 4
Guo, W., Tang, H., Yi, Z., Zhang, T., Yuan, P., Wang, C., Ren, S., 常希文, Ren, J., Tang, W., et al. (2026) · Cell · doi:10.1016/j.cell.2026.05.030 · Cited by 4
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Grigg, S. E., Shembrey, C., Fareh, M., Blombery, P. A., Corn, J. E., Seymour, J. F., & Casan, J. M. L. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01179-2 · Cited by 4
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Rodrigues, L. C. (2020) · Revista de Estudos Empíricos em Direito · doi:10.19092/reed.v7i3.343 · Cited by 4
Qureshi, A., & Connolly, J. B. (2023) · Malaria Journal · doi:10.1186/s12936-023-04665-5 · Cited by 5
Tourdot, S., Baltrunkonis, D., Denies, S., Devanarayan, V., Grudzinska‐Goebel, J., Kromminga, A., Lotz, G. P., Malherbe, L. P., Michaut, L., Weldingh, K. N., et al. (2024) · mAbs · doi:10.1080/19420862.2024.2324801 · Cited by 4
How to Shift the Equilibrium of DNA Break Repair in Favor of Homologous Recombination
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Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy
Sivaprakasam, A., Mahendran, R., Chandrasekaran, V., Chanchal, D. K., Mathew, S., Sharma, M. C., Shiekmydeen, J., & Ali, S. S. (2024) · Current Gene Therapy · doi:10.2174/0115665232305409240918040639 · Cited by 4
Extensive humoral immune response to AAVs and Cas proteins in nonhuman primates
Xiao, P., Bai, R., Zhang, T., Zhou, Y., Zhou, Z., Zhuo, Y., Gong, N., Niu, Y., Ren, S., Wu, R., et al. (2021) · 中国科学通报：英文版 · doi:10.1016/j.scib.2021.02.009 · Cited by 4
Small RNA-directed DNA elimination: the molecular mechanism and its potential for genome editing
Bastiaanssen, C., & Joo, C. (2021) · RNA Biology · doi:10.1080/15476286.2021.1885208 · Cited by 4
Modulation of Immune Reaction in Hydrodynamic Gene Therapy for Hemophilia A
Zhao, M., Sun, Y., Yin, M., Zhao, J.-J., Li, S.-A., Li, G., Zhang, F., Xu, J., Meng, F., Zhang, B., et al. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.145 · Cited by 4
Wang, Q., Zhang, L., Zhang, G., Mao, J.-H., Xi, X., Jiang, L., Lv, G., Lu, J., Shen, Y., Chen, Z., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2110887118 · Cited by 4
Self-citationKayesh, M. E. H., Hashem, M. A., Kohara, M., & Tsukiyama–Kohara, K. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.953218 · Cited by 4
The Gene Manipulation and Cellular Immunotherapy Combination in the Treatment of Cancer.
Khatami, F., Aghamir, Z. S., Jahanshahi, F., Feiz-Abadi, S. A., Birang, F., Khoshchehreh, M., Shabestari, A. N., & Aghamir, S. M. K. (2022) · PubMed Central · doi:10.30498/ijb.2022.294933.3094 · Cited by 4
Hepatitis B and HIV-1 2019 IAS Cure Forum: lessons and benefits from interdisciplinary research
Paximadis, M., Patrigeon, S. P., Rajasuriar, R., Tatoud, R., Scully, E. P., & Arbuthnot, P. B. (2019) · Journal of Virus Eradication · doi:10.1016/s2055-6640(20)30027-3 · Cited by 4
CRISPR-Edited Immune Effectors: The End of the Beginning
Mo, F., Heslop, H. E., & Mamonkin, M. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.03.009 · Cited by 4
CRISPR/Cas9 technology in neurological disorders: An update for clinicians
Srivastava, A. K., Swarup, V., Kumar, V., Faruq, M., Singh, H. N., & Singh, I. (2020) · Annals of Movement Disorders · doi:10.4103/aomd.aomd_39_19 · Cited by 4
Delivery of Genetic Information: Viral Vector and Nonviral Vector Gene Therapies
Gemayel, M. C., Byrne, L. C., Ciulla, T. A., & Sahel, J. (2021) · International Ophthalmology Clinics · doi:10.1097/iio.0000000000000360 · Cited by 5
In vitro and in cellula site-directed RNA editing using the λNDD-BoxB system
Ojha, N., Quiroz, J. F. D., & Rosenthal, J. J. C. (2021) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2021.06.009 · Cited by 4
Tan, Z. Y., Huang, T., & Ngeow, J. Y. Y. (2018) · Endocrine Related Cancer · doi:10.1530/erc-18-0039 · Cited by 5
Šalic, Š., Sieber, A., Barbaria, S., Vasilyev, A., Papadimou, E., Milosavljevic, N., Klapholz, B., Sivapalan, R., Collingwood, T. N., Henley, T., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.03.15.435463 · Cited by 4
How CRISPR Is Revolutionizing the Generation of New Models for Cancer ResearchPreprint
Rivera, F. J. S., & Dow, L. E. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041384 · Cited by 4
Sustained efficacy of CRISPR-Cas13b gene therapy for FSHD is challenged by immune response to Cas13bPreprint
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CRISPR/Cas in dermatology: A scoping review of candidate diseases for clinical applications
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Rheault, M. N. (2025) · Journal of the American Society of Nephrology · doi:10.1681/asn.0000000897 · Cited by 3
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Bax, B. D., Sutormin, D. A., McDonald, N. Q., Burley, G. A., & Shelkovnikova, T. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911541 · Cited by 3
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Mochi, J. A., Jani, J., Joshi, S. M., & Pappachan, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-91808-4.00005-5 · Cited by 3
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Zhao, M., Wen, J., Chen, I. S. Y., Liu, J., & Lu, Y. (2025) · ACS Applied Bio Materials · doi:10.1021/acsabm.4c01544 · Cited by 3
Mousavi, S. M., Kalashgrani, M. Y., Rahmanian, V., Mirshafiei, M., Omidifar, N., Shokripour, M., Lai, C. W., Thomas, P., Aljabri, M. D., Rahman, M. M., et al. (2025) · Journal of Industrial and Engineering Chemistry · doi:10.1016/j.jiec.2025.06.017 · Cited by 4
CD4+ T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming
Kim, S. I., Haerr, M. E., Al-Ghezi, M., Chen, C., Zhang, Y., Phipps, J. L., Arora, C., Gribbin, K. P., Kim, G. T., Markosyan, N., et al. (2025) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-24-1342 · Cited by 3
Multiplex engineering and multifunction T cells for precise and effective immunotherapies
Jafarzadeh, L., Smaani, A., & Delisle, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1680410 · Cited by 3
CD33 epitope editing unlocks UM171-expanded cord blood grafts for AML immunotherapy
Lehnertz, B., Langouët, M., Corneau, S., MacRae, T., Joe, M., Schmidt, E. N., Spinella, J.-F., Mayotte, N., Moore, S., Tellechea, M. F., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.11.010 · Cited by 3
Multi-omic Analyses Reveal Minimal Impact of the CRISPR-Cas9 Nuclease on Cultured Human Cells
Qiang, J., Ma, Z., Xie, X., Shi, L., Geng, Y., Hu, J., Liu, R., Liu, N., & Zhang, Y. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00751 · Cited by 3
Selvaraj, D., Dawar, R., Kumar, S. P., & Devi, A. (2021) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2021-0062 · Cited by 3
Bringing gene therapy to where it’s needed
Radtke, S., & Kiem, H. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.01.005 · Cited by 3
CRISPR/Cas9 Technology: Challenges and drawbacks
Ghorui, S. B. A. (2023) · Journal Of Advanced Zoology · doi:10.17762/jaz.v44is6.2680 · Cited by 3
Role of CRISPR/Cas9 based therapy in breast cancer: a future direction
Asrar, A., Gupta, D., Sharma, P., Agarwal, S. K., Shukla, P. C., & Bagga, N. (2024) · The Nucleus · doi:10.1007/s13237-024-00484-4 · Cited by 3
Bioinformatic tools for CRISPR-mediated genome editing
Gila, F., Shakeri, S., Khoddam, S., Jamali, Z., Sichani, A. S., Dehghan, Z., & Fallahi, J. (2025) · Gene Reports · doi:10.1016/j.genrep.2025.102204 · Cited by 3
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Exley, A., & McBlane, J. W. (2020) · Immunotherapy Advances · doi:10.1093/immadv/ltaa011 · Cited by 4
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Winder, M. L., & Trokovic, R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822135-8.00009-4 · Cited by 3
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Ledford, H. K. (2018) · Nature · doi:10.1038/d41586-018-00335-8 · Cited by 3
Ballouhey, O., Bartoli, M., & Lévy, N. (2020) · médecine/sciences · doi:10.1051/medsci/2020081 · Cited by 4
Dowling, J. J. (2022) · Gene Therapy · doi:10.1038/s41434-022-00323-8 · Cited by 3
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Choi, E., & Koo, T. (2022) · Springer eBooks · doi:10.1007/978-3-030-93333-3_4 · Cited by 3
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Liu, S., Duan, X., Peng, F., Yf, W., Liu, Y., Wan, X., Zhang, J., Li, X., & Sun, X. (2022) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2022.08.004 · Cited by 3
Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9Preprint
Agudelo, D., Carter, S., Velimirovic, M., Duringer, A., Levesque, S., Rivest, J.-F., Loehr, J., Mouchiroud, M., Cyr, D., Waters, P. J., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/321208 · Cited by 3
Chakraborty, S. (2019) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/42rct · Cited by 3
Therapeutic Potential of CRISPR/Cas in Hashimoto's Thyroiditis: A Comprehensive Review
Upreti, A., & Mukherjee, S. (2024) · Current Gene Therapy · doi:10.2174/0115665232266508231210154930 · Cited by 2
Beschorner, N., Künzle, P., Voges, M., Hauber, I., Indenbirken, D., Nakel, J., Virdi, S., Bradtke, P., Lory, N. C., Rothe, M., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0298542 · Cited by 3
Therapeutic liver cell transplantation to treat murine PKU
Willimann, M., Grisch‐Chan, H. M., Rimann, N., Rothgangl, T., Hruzova, M., Schwank, G., & Thöny, B. (2024) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12802 · Cited by 2
Kandina, D. A., Velizhanina, M. E., Sopova, J. V., & Леонова, Е. И. (2025) · Cell and Tissue Biology · doi:10.1134/s1990519x25600024 · Cited by 2
Shamsi, A., Alrouji, M., AlOmeir, O., Tasqeruddin, S., Khuzin, D., & Zuberi, A. (2025) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2025.1681891 · Cited by 2
CRISPR-based gene therapy for huntington’s disease: current advances and future prospects
Zaheer, A., AboQuella, N. M., Wadan, A. S., Saad, H. A., Kumar, D., Panjwani, S., Rath, S., & Ahmed, S. I. (2025) · Neurogenetics · doi:10.1007/s10048-025-00858-z · Cited by 2
Screening strategy to identify Cas9 variants with higher HDR activity based on diphtheria toxin
Matsumoto, D., Kubota, K., Sato, Y., Kato-Inui, T., Nigorikawa, K., Miyaoka, Y., & Nomura, W. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01197-9 · Cited by 2
Ye, F., & Zheng, H. (2025) · Health engineering. · doi:10.26599/he.2025.9460011 · Cited by 2
Metadata
- Authors
- Charlesworth, C. T., Deshpande, P. S., Dever, D. P., Camarena, J., Lemgart, V. T., Cromer, M. K., Vakulskas, C. A., Collingwood, M. A., Zhang, L., Bode, N. M., Behlke, M. A., Dejene, B., Cieniewicz, B., Romano, R., Lesch, B. J., Gomez-Ospina, N., Mantri, S., Pavel-Dinu, M., Weinberg, K. I., & Porteus, M. H.
- Affiliations
- Stanford Medicine (US)
- Integrated DNA Technologies (United States) (US)
- Corresponding author
- Weinberg, Kenneth I.
- Porteus, Matthew H.
- ORCID
- Charlesworth, Carsten T.
- Dever, Daniel P.
- Camarena, Joab
- Lemgart, Viktor T.
- Cromer, M. Kyle
- Vakulskas, Christopher A.
- Collingwood, Michael A.
- Zhang, Liyang
- Bode, Nicole M.
- Behlke, Mark A.
- Dejene, Beruh
- Cieniewicz, Brandon
- Romano, Rosa
- Lesch, Benjamin J.
- Gomez-Ospina, Natalia
- Mantri, Sruthi
- Pavel-Dinu, Mara
- Weinberg, Kenneth I.
- Porteus, Matthew H.
- Venue
- Nature Medicine
- Published
- 2019-01-28
- Volume
- 25
- Issue
- 2
- Pages
- 249-254
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC7199589
- OpenAlex
- W2949380898
- Cited by
- 1,093
- References
- 48
- Citations by year
- 2026: 130 · 2025: 128 · 2024: 132 · 2023: 111 · 2022: 125 · 2021: 166 · 2020: 131 · 2019: 110
- FWCI
- 44.16
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nd)
- Funders
- Amon G. Carter Foundation
- National Institutes of Health (5r01ai120766-02)
- National Institute of General Medical Sciences (T32GM119995)
- National Institute of Allergy and Infectious Diseases (R01-AI120766)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- CRISPR/Cas9, SaCas9, SpCas9, Staphylococcus aureus, Streptococcus pyogenes, humoral immune response, cell-mediated immunity, genome editing safety
- MeSH terms
- CRISPR-Associated Protein 9, Adult, Cell Separation, Female, Humans, Male, T-Lymphocytes, Adaptive Immunity, Immunity, Humoral
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