The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
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
Cited by
Sorted by citations
Items 401–500 of 1,000
CRISPR and KRAS: a match yet to be made
Bender, G., Yamaci, R. F., & Taneri, B. (2021) · Journal of Biomedical Science · doi:10.1186/s12929-021-00772-0 · Cited by 25
Zhou, L., Su, J., Long, J., Tao, R. X., Tang, W., Qin, F., Liu, N., Wang, Y., Jiao, Y., Hu, Y. F., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.01.001 · Cited by 24
Oncolytic viral therapy for gliomas: Advances in the mechanisms and approaches to delivery
Romanishin, A. O., Vasilev, A., Khasanshin, E., Evtekhov, A., Pusynin, E., Rubina, K., Kakotkin, V., Agapov, M., & Semina, E. (2024) · Virology · doi:10.1016/j.virol.2024.110033 · Cited by 24
Chemogenetic System Demonstrates That Cas9 Longevity Impacts Genome Editing Outcomes
Sreekanth, V., Zhou, Q., Kokkonda, P., Bermudez-Cabrera, H. C., Lim, D., Law, B. K., Holmes, B. R., Chaudhary, S. K., Pergu, R., Leger, B. S., et al. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c00129 · Cited by 24
From bench to bedside: Developing CRISPR/Cas-based therapy for ocular diseases
Zhao, Q., Wei, L., & Chen, Y. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107638 · Cited by 23
Fuentes, C., & Schaffer, D. V. (2018) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2018.08.003 · Cited by 27
Therapeutic application of the CRISPR system: current issues and new prospects
Lee, M., & Kim, S. (2019) · Human Genetics · doi:10.1007/s00439-019-02028-2 · Cited by 23
Applications of CRISPR‐Cas9 in gynecological cancer research
Zhang, W., Liu, Y., Zhou, X., Zhao, R., & Wang, H. (2020) · Clinical Genetics · doi:10.1111/cge.13717 · Cited by 23
CRISPR/Cas9 in cancer therapy: A review with a special focus on tumor angiogenesis
Hariprabu, K. N. G., Muthusamy, S., & Vimalraj, S. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.10.029 · Cited by 23
New Editing Tools for Gene Therapy in Inherited Retinal Dystrophies
Pulman, J., Sahel, J., & Dalkara, D. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0141 · Cited by 25
Integrating CRISPR/Cas systems with programmable DNA nanostructures for delivery and beyond
Piskunen, P., Latham, R., West, C. E., Castronovo, M., & Linko, V. (2022) · iScience · doi:10.1016/j.isci.2022.104389 · Cited by 23
Herzeg, A., Almeida-Porada, G. D., Charo, R. A., David, A. L., Gonzalez‐Velez, J. M., Gupta, N. M., Lapteva, L., Lianoglou, B. R., Peranteau, W. H., Porada, C. D., et al. (2022) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.2127 · Cited by 24
García, M., Bonafont, J., Martínez‐Palacio, J., Xu, R., Turchiano, G., Svensson, S., Thrasher, A. J., Larcher, F., Río, M. D., Hernández-Alcoceba, R., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.09.005 · Cited by 25
Recent advances in gene therapy for bone tissue engineering
Ranjbarnejad, F., Khazaei, M., Shahryari, A., Khazaei, F., & Rezakhani, L. (2022) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3363 · Cited by 23
In Vivo Hematopoietic Stem Cell Genome Editing: Perspectives and Limitations
Psatha, N., Paschoudi, K., Παπαδοπούλου, Α., & Yannaki, E. (2022) · Genes · doi:10.3390/genes13122222 · Cited by 24
Szapacs, M., Jian, W., Spellman, D. S., Cunliffe, J., Verburg, E., Kaur, S., Kellie, J. F., Li, W., Mehl, J. T., Qian, M. G., et al. (2023) · Bioanalysis · doi:10.4155/bio-2023-0167 · Cited by 23
Self-citationCattaneo, C., Enzo, E., Rosa, L. D., Sercia, L., Consiglio, F., Forcato, M., Bicciato, S., Paiardini, A., Basso, G., Tagliafico, E., et al. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.11.027 · Cited by 25
Schulze, S., & Lammers, M. (2020) · ChemTexts · doi:10.1007/s40828-020-00126-7 · Cited by 23
You can't keep a bad idea down: Dark history, death, and potential rebirth of eugenics
Liscum, M., & Garcia, M. L. (2021) · The Anatomical Record · doi:10.1002/ar.24849 · Cited by 26
The Potential of CRISPR-Guided Therapies in the Dermatology Clinic
Bhat, P., & Garibyan, L. (2022) · JID Innovations · doi:10.1016/j.xjidi.2022.100103 · Cited by 22
Zhou, W., Yang, J., Zhang, Y., Hu, X., & Wang, W. (2022) · MedComm · doi:10.1002/mco2.155 · Cited by 23
Alayoubi, A. M., Khawaji, Z. Y., Mohammed, M. A., & Mercier, F. (2023) · Annals of Hematology · doi:10.1007/s00277-023-05457-2 · Cited by 24
Iron oxide-coupled CRISPR-nCas9-based genome editing assessment in mucopolysaccharidosis IVA mice
Leal, A. F., Çelik, B., Nidhi, F., Khan, S. A., Tomatsu, S., & Alméciga-Díaz, C. J. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.101153 · Cited by 23
Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing
Vlashi, R., Zhang, X., Li, H., & Chen, G. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09860-y · Cited by 24
Applications of CRISPR systems in respiratory health: Entering a new ‘red pen’ era in genome editing
Moses, C., & Kaur, P. (2019) · Respirology · doi:10.1111/resp.13527 · Cited by 22
Emami, M. R., Young, C. S., Ji, Y. C., Liu, X., Mokhonova, E. I., Pyle, A. D., Meng, H., & Spencer, M. J. (2019) · Advanced Therapeutics · doi:10.1002/adtp.201900061 · Cited by 22
Saxena, S., & Kumar, S. (2020) · GeroScience · doi:10.1007/s11357-020-00167-3 · Cited by 23
Cannon, P. M., Asokan, A., Czechowicz, A. D., Hammond, P. T., Kohn, D. B., Lieber, A., Malik, P., Marks, P. W., Porteus, M. H., Verhoeyen, E., et al. (2021) · Human Gene Therapy · doi:10.1089/hum.2020.263 · Cited by 26
Self-citationCRISPR Technology for Ocular Angiogenesis
Chung, S. H., Sin, T.-N., Ngo, T., & Yiu, G. C. (2020) · Frontiers in Genome Editing · doi:10.3389/fgeed.2020.594984 · Cited by 21
Rathbone, T., Ates, I., Fernando, L. P., Addlestone, E., Lee, C. M., Richards, V. P., & Cottle, R. N. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0134 · Cited by 23
Keratinocytes sense and eliminate CRISPR DNA through STING/IFN-κ activation and APOBEC3G induction
Sarkar, M. K., Uppala, R., Zeng, C., Billi, A. C., Tsoi, L. C., Kidder, A., Xing, X., White, B. E. P., Shao, S., Plazyo, O., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci159393 · Cited by 23
Yao, J., Atasheva, S., Wagner, N. J., Paolo, N. C. D., Stewart, P. L., & Shayakhmetov, D. M. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.10.023 · Cited by 23
Functionalized extracellular nanovesicles as advanced CRISPR delivery systems
Wang, S., Kong, H., Zhuo, C., Liu, L., Lv, S., Cheng, D., Lao, Y., Tao, Y., & Li, M. (2024) · Biomaterials Science · doi:10.1039/d4bm00054d · Cited by 22
Schwarzer, R., Gramatica, A., & Greene, W. C. (2020) · Viruses · doi:10.3390/v12020188 · Cited by 21
Novel genome-editing-based approaches to treat motor neuron diseases: Promises and challenges
Miccio, A., Antoniou, P., Ciura, S., & Kabashi, E. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.04.003 · Cited by 21
Kato, Y., Tabata, H., Sato, K., Nakamura, M., Saito, I., & Nakanishi, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910570 · Cited by 21
An Update of Nucleic Acids Aptamers Theranostic Integration with CRISPR/Cas Technology
Roueinfar, M., Templeton, H., Sheng, J. A., & Hong, K. L. (2022) · Molecules · doi:10.3390/molecules27031114 · Cited by 21
Gene knockout in cellular immunotherapy: Application and limitations
Zhang, X., Jin, X. K., Sun, R., Zhang, M., Lu, W., & Zhao, M. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215736 · Cited by 22
Bazick, H., Mao, H., Niehaus, J. K., Wolter, J. M., & Zylka, M. J. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.09.032 · Cited by 20
Zhou, Z., Chen, Y., Ba, Y., Xu, H., Zuo, A., Liu, S., Zhang, Y., Weng, S., Ren, Y., Luo, P., et al. (2024) · Cell Proliferation · doi:10.1111/cpr.13791 · Cited by 20
Han, H., Sun, X., Guo, X., Wen, J., Zhao, X., & Zhou, W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1552741 · Cited by 23
Towards clinical translation of nanomedicines: Formulation scale-up and model systems
Kelly, O. M., Hanna, A. R., Byrne, A. K., Green, J. A., Périssé, I. V., Wells, K. D., Murray, S. A., Xu, J., Chen, Y. E., Polejaeva, I. A., et al. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115862 · Cited by 20
Understanding the Potential of Genome Editing in Parkinson’s Disease
Arango, D., Bittar, A., Esmeral, N. P., Ocasión, C., Muñoz-Camargo, C., Cruz, J. C., Reyes, L. H., & Bloch, N. I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179241 · Cited by 24
Shanahan, M. A., Aagaard, K. M., McCullough, L. B., Chervenak, F. A., & Shamshirsaz, A. A. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2021.09.001 · Cited by 22
Genome editing in cancer: Challenges and potential opportunities
Breier, D., & Peer, D. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.08.013 · Cited by 21
Applications of CRISPR Cas-9 in Ovarian Cancer Research
Sherazi, S. A. M., Rafique, F., Haris, M., Arshad, A., Qaiser, H., Uzair, M., & Arshad, M. M. U. D. (2023) · Protein and Peptide Letters · doi:10.2174/0929866530666230607104453 · Cited by 20
The application of CRISPR/Cas9–based genome-wide screening to disease research
Chen, X., Zheng, M., Lin, S., Huang, M., Chen, S., & Chen, S. (2024) · Molecular and Cellular Probes · doi:10.1016/j.mcp.2024.102004 · Cited by 21
Overcoming the Undesirable CRISPR-Cas9 Expression in Gene Correction
Xia, E., Duan, R. C., Shi, F., Seigel, K. E., Grasemann, H., & Hu, J. (2018) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2018.10.015 · Cited by 20
Panagopoulou, T. I., & Rafiq, Q. A. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.06.010 · Cited by 20
Designing custom CRISPR libraries for hypothesis-driven drug target discovery
Iyer, V. S., Jiang, L., Shen, Y., Boddul, S. V., Panda, S. K., Kasza, Z., Schmierer, B., & Wermeling, F. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.08.009 · Cited by 21
Sheykhhasan, M., Foroutan, A., Manoochehri, H., Khoei, S. G., Poondla, N., & Saidijam, M. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119451 · Cited by 21
Chen, M., Shi, H., Gou, S., Wang, X., Li, L., Jin, Q., Wu, H., Zhang, H., Li, Y., Wang, L., et al. (2021) · Genome Medicine · doi:10.1186/s13073-021-00876-0 · Cited by 22
Where Will We Draw the Line? Public Opinions of Human Gene Editing
Riggan, K. A., Sharp, R. R., & Allyse, M. A. (2019) · Qualitative Health Research · doi:10.1177/1049732319846867 · Cited by 20
Neutralizing Antibodies: Role in Immune Response and Viral Vector Based Gene Therapy
Tsaregorodtseva, T. S., Gubaidullina, A. A., Kayumova, B. R., Shaimardanova, A. A., Issa, S. S., Solovyeva, V. V., Sufianov, A. A., Суфианова, Г. З., & Rizvanov, A. A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115224 · Cited by 20
Yashooa, R. K., Nabi, A. Q., Smail, S. W., Azeez, S. S., Nooh, W. A., Mustafa, S. A., Al-Farha, A. A.-B., Capitanio, N., & Shekha, M. S. (2026) · Frontiers in Neurology · doi:10.3389/fneur.2025.1737468 · Cited by 21
Controlling CRISPR with small molecule regulation for somatic cell genome editing
Khajanchi, N., & Saha, K. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.06.014 · Cited by 19
Toward the Treatment of Inherited Diseases of the Retina Using CRISPR-Based Gene Editing
Hernández-Juárez, J., Rodríguez‐Uribe, G., & Borooah, S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.698521 · Cited by 19
Schwab, M. E., & MacKenzie, T. C. (2021) · Clinical Obstetrics & Gynecology · doi:10.1097/grf.0000000000000655 · Cited by 20
Gene Editing for Inherited Red Blood Cell Diseases
Bustamante, O. Q., Fañanas-Baquero, S., Dessy-Rodríguez, M., Ojeda-Pérez, I., & Segovia, J. C. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.848261 · Cited by 20
Huang, C., Li, Q., & Li, J. (2022) · Medical Review · doi:10.1515/mr-2022-0029 · Cited by 20
CRISPR activation and interference as investigative tools in the cardiovascular system
Carroll, M. S., & Giacca, M. (2022) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2022.106348 · Cited by 20
Asif, M., Khan, W. J., Aslam, S., Aslam, A., & Chowdhury, M. A. (2024) · Cureus · doi:10.7759/cureus.57869 · Cited by 19
Blossom of CRISPR technologies and applications in disease treatment
Liu, H., Wang, L., & Luo, Y. (2018) · Synthetic and Systems Biotechnology · doi:10.1016/j.synbio.2018.10.003 · Cited by 19
Evasion of Pre-Existing Immunity to Cas9: A Prerequisite for Successful Genome Editing In Vivo?
Wignakumar, T., & Fairchild, P. J. (2019) · Current Transplantation Reports · doi:10.1007/s40472-019-00237-2 · Cited by 19
Soblechero‐Martín, P., Albiasu-Arteta, E., Anton, A., Ovejero, L. D. L. P., Garcia-Jimenez, I., González-Iglesias, G., Larrañaga-Aiestaran, I., López‐Martínez, A., Poyatos‐García, J., Ruiz-del-Yerro, E., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-97730-5 · Cited by 19
Ely, A., Singh, P., Smith, T. S., & Arbuthnot, P. B. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2020.05.010 · Cited by 19
CRISPR and transposon in vivo screens for cancer drivers and therapeutic targets
Noorani, I., Bradley, A., & Rosa, J. D. L. (2020) · Genome biology · doi:10.1186/s13059-020-02118-9 · Cited by 20
CRISPR genome engineering for retinal diseases
Kantor, A., McClements, M. E., Peddle, C. F., Fry, L. E., Salman, A., Cehajic‐Kapetanovic, J., Xue, K., & MacLaren, R. E. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.01.024 · Cited by 19
Singh, P., Kairuz, D., Arbuthnot, P. B., & Bloom, K. M. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i23.3182 · Cited by 19
In vivo liver targeted genome editing as therapeutic approach: progresses and challenges
Simoni, C., Barbon, E., Muro, A. F., & Cantore, A. (2024) · Frontiers in Genome Editing · doi:10.3389/fgeed.2024.1458037 · Cited by 20
Mechanisms involved in aminoacidurias: impacts of genetic and environmental factors
Ajayi, J. A., Ananias, E. N., Issa-Lawal, M., Gambari, A. M., Aribatise, A. B., Ojulari, L. S., & Alagbonsi, A. I. (2025) · Current Research in Physiology · doi:10.1016/j.crphys.2025.100168 · Cited by 18
Clinical trials and promising preclinical applications of CRISPR/Cas gene editing
Çerçi, B., Uzay, İ. A., Kara, M. K., & Dinçer, P. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121204 · Cited by 19
Development of New Genome Editing Tools for the Treatment of Hyperlipidemia
Preta, G. (2023) · Cells · doi:10.3390/cells12202466 · Cited by 19
Next-generation CRISPR technology for genome, epigenome and mitochondrial editing
Lau, C., Liang, Q., & Zhu, H. (2024) · Transgenic Research · doi:10.1007/s11248-024-00404-x · Cited by 19
Antony, J. S., Haque, A. K. M. A., Lamsfus‐Calle, A., Daniel-Moreno, A., Mezger, M., & Kormann, M. (2018) · Advances in Cell and Gene Therapy · doi:10.1002/acg2.10 · Cited by 20
A method for the quantitative detection of Cas12a ribonucleoproteins
Qiao, J., Lin, S., Sun, W., Ma, L., & Liu, Y. (2020) · Chemical Communications · doi:10.1039/d0cc04019c · Cited by 18
Smith, T. S., Singh, P., Chmielewski, K. O., Bloom, K. M., Cathomen, T., Arbuthnot, P. B., & Ely, A. (2021) · Viruses · doi:10.3390/v13071344 · Cited by 18
Base and Prime Editing in the Retina—From Preclinical Research toward Human Clinical Trials
Yee, T., & Wert, K. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012375 · Cited by 21
Hidden antibiotics: Where to uncover?
Mol, M. L. D., Snoeck, N., Maeseneire, S. L. D., & Soetaert, W. (2018) · Biotechnology Advances · doi:10.1016/j.biotechadv.2018.10.008 · Cited by 18
Switchable genome editing via genetic code expansion
Suzuki, T., Asami, M., Patel, S. G., Luk, L. Y. P., Tsai, Y., & Perry, A. C. F. (2018) · Scientific Reports · doi:10.1038/s41598-018-28178-3 · Cited by 18
Viral and nonviral nanocarriers for in vivo CRISPR-based gene editing
Guo, Z., Zhu, A. T., Fang, R. H., & Zhang, L. (2024) · Nano Research · doi:10.1007/s12274-024-6748-5 · Cited by 18
Self-citationCRISPR delivery systems for organ-specific targeting: Advances and challenges
Du, J., Wu, Q., Liu, C., Wang, N., & Gong, C. (2025) · Precision medicine and engineering. · doi:10.1016/j.preme.2025.100048 · Cited by 20
Jalil, S., Keskinen, T., Juutila, J., Sartori-Maldonado, R., Euro, L., Suomalainen, A., Lapatto, R., Kuuluvainen, E., Hietakangas, V., Otonkoski, T., et al. (2024) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2024.03.004 · Cited by 18
In vivo evaluation of guide-free Cas9-induced safety risks in a pig model
Ge, W., Gou, S., Zhao, X., Jin, Q., Zhuang, Z., Zhao, Y., Liang, Y., Ouyang, Z., Liu, X., Chen, F., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01905-1 · Cited by 17
Genetically Engineering the Nervous System with CRISPR-Cas
Sandoval, A., Elahi, H., & Ploski, J. E. (2020) · eNeuro · doi:10.1523/eneuro.0419-19.2020 · Cited by 18
Use of Customizable Nucleases for Gene Editing and Other Novel Applications
Reddy, P., Vilella, F., Belmonte, J. C. I., & Simón, C. (2020) · Genes · doi:10.3390/genes11090976 · Cited by 18
The resurgent landscape of xenotransplantation of pig organs in nonhuman primates
Zhang, X., Wang, Q., Zhao, J., Li, X., Wei, P., Yang, Z.-X., Lin, Z., Yang, L., Ding, R., Tao, K., et al. (2020) · Science China Life Sciences · doi:10.1007/s11427-019-1806-2 · Cited by 17
CRISPR/Cas9 in epigenetics studies of health and disease
Sar, P., & Dalai, S. K. (2021) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2021.01.022 · Cited by 18
Recent advances in CRISPR technologies for genome editing
Song, M., & Koo, T. (2021) · Archives of Pharmacal Research · doi:10.1007/s12272-021-01336-4 · Cited by 18
Splice-switching as cancer therapy
Jbara, A., Siegfried, Z., & Karni, R. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.05.008 · Cited by 17
Preclinical Assessment of a Gene Editing Approach in a Mouse Model of MNGIE
Parés, M., Fornaguera, C., Vila‐Julià, F., Oh, S., Fan, S. H. Y., Tam, Y. K., Comes, N., Vidal, F., Martí, R., Borrós, S., et al. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.152 · Cited by 18
Decrypting the mechanistic basis of CRISPR/Cas9 protein
Panda, G., & Ray, A. (2022) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2022.05.001 · Cited by 17
New Directions in Pulmonary Gene Therapy
Vu, A., & McCray, P. B. (2020) · Human Gene Therapy · doi:10.1089/hum.2020.166 · Cited by 19
Xiang, T., Wang, X., Xiang, L., Zhang, C., Wu, J., & Zhou, S. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.166510 · Cited by 16
Noormohamadi, H., Samarkhazan, H. S., Kargar, M., Maroufi, F., Servatian, N., & Davami, F. (2025) · Discover Oncology · doi:10.1007/s12672-025-03383-5 · Cited by 17
Dual AAV vectors for efficient delivery of large transgenes
Mittas, D. M., Riedmayr, L. M., Gavrilov, Z., Weber, V. J., Otify, D. Y., Mehlfeld, V., Szalontai, B., Ucambarlic, E., Gandor, C. L. A., Heigl, T., et al. (2025) · Nature Protocols · doi:10.1038/s41596-025-01243-8 · Cited by 18
Treating Hearing Loss: From Cochlear Implantation to Gene Therapy
Zeng, F., Qi, J., Wu, C., Shu, Y., & Chai, R. (2025) · Advanced Science · doi:10.1002/advs.202509960 · Cited by 17
Genetic therapies for neurological disorders
FitzPatrick, L., & Bird, A. P. (2021) · Human Genetics · doi:10.1007/s00439-021-02399-5 · Cited by 19
Genome editing of PD-L1 mediated by nucleobase-modified polyamidoamine for cancer immunotherapy
Wei, S., Shao, X., Liu, Y., Xiong, B., Cui, P., Liu, Z., & Li, Q. (2022) · Journal of Materials Chemistry B · doi:10.1039/d1tb02688g · Cited by 16
Shen, X., Lin, Q., Liang, Z., Wang, J., Yang, X., Liang, Y., Liang, H., Pan, H., Yang, J., Zhu, Y., et al. (2022) · The CRISPR Journal · doi:10.1089/crispr.2021.0142 · Cited by 16
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
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
