The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Multiplex Genome Engineering Using CRISPR/Cas Systems
Open accessAbstract
Genome Editing: Clustered regularly interspaced short palindromic repeats (CRISPR) function as part of an adaptive immune system in a range of prokaryotes: Invading phage and plasmid DNA is targeted for cleavage by complementary CRISPR RNAs (crRNAs) bound to a CRISPR-associated endonuclease (see the Perspective by van der Oost ). Cong et al. (p. 819 , published online 3 January) and Mali et al. (p. 823 , published online 3 January) adapted this defense system to function as a genome editing tool in eukaryotic cells.
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In the citing paper
“CRISPR/Cas9 is a class of ribonucleoprotein complexes formed by a Cas9 protein and a single guide RNA (sgRNA) (Jinek et al., 2012; Cho et al., 2013; Cong et al., 2013; Wang et al., 2016a).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Cong et al., 2013
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
“Cas9 is guided by a 20 nt fraction of the gRNA”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
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
“and it maintains cleaving activity even with 3-5 mismatches at the PAM-distal end of the gRNA molecule [59,81,102].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
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
“In January 2013, almost simultaneously, five research articles authored by different research teams appeared, all reporting that they had achieved the goal.”
From CRISPR–Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing (2022) · cites this paper as [35]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Repurposing bacterial “CRISPR” systems to facilitate RNA-guided cleavage of complementary DNA has revolutionized the field of gene editing in mammalian cells 1–4.”
From A high-fidelity Cas9 mutant delivered as a ribonucleoprotein complex enables efficient gene editing in human hematopoietic stem and progenitor cells (2018) · cites this paper as [2]
The cited source says what the claim attributes to it.
In the citing paper
“Target specificity of the CRISPR/Cas system is very high and a single mutation can disrupt targeting 20”
From Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus (2013) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“Cas9 can create DNA cleavage at desired genomic positions that are guided by precise base pairing between sgRNA and DNA, adjacent to a protospacer-adjacent motif (PAM) (Jinek et al., 2012; Cho et al., 2013; Cong et al., 2013; Wang et al., 2016a).”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Cong et al., 2013
The cited source says what the claim attributes to it.
In the citing paper
“By introducing an aspartate-to-alanine (D10A) mutation in the RuvC active domain of Cas9, the resulting mutant, Cas9 nickase, (Cas9n) will nick the target DNA, originating single-stranded breaks rather than DSB [54,81].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“Cas9n nicks the target DNA, originating single-stranded breaks rather than DSB [54,81].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“by introducing a specific mutation in the RuvC domain of Cas9, a Cas9 nickase variant (Cas9n) is created.”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“The markedly high efficiency of CRISPR/Cas systems coupled with the above-mentioned advantages over other methods justify the CRISPR “epidemic” that the scientific community experienced in 2013 [62,81,100,101].”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“The pigs were engineered to carry 69 genomic edits, using the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)-mediated nonhomologous end joining and homology-directed repair30,31, and recombinase-mediated cassette exchange32 (Fig. 2a, Extended Data Fig. 1a and Supplementary Table 2).”
From Design and testing of a humanized porcine donor for xenotransplantation (2023) · cites this paper as [30]
In the citing paper
“When a double-stranded break is introduced into genomic DNA, cells can repair the break by using a DNA molecule with high sequence similarity as a template. If an artificial template is provided while the DNA break is introduced, this pathway provides a mean to incorporate desired DNA sequences into the genome34,35”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [34]
In the citing paper
“The discovery, made less than 10 years ago, that a simple two-component system of a Cas protein (Streptococcus pyogenes Cas9) bound to a single guide RNA (sgRNA) can function as a programmable nuclease33 that can be deployed to cleave specific sequences in mammalian genomes34,35 has been transformative for biomedical research and the development of gene therapies.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [34]
In the citing paper
“The CRISPR/Cas9 system has been used for multiplex genome cleavage.20”
From The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo (2014) · cites this paper as [20]
In the citing paper
“Recently, the CRISPR/Cas system has been successfully applied to human cells19,20,21,22 and several model organisms for genome editing.23,24,25,26”
From The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo (2014) · cites this paper as [20]
In the citing paper
“selection of LTR-A-and -B-directed, 30-bp protospacer and also precrRNA system reflecting the original bacterial immune mechanism to enhance specificity/efficiency vs. 20-bp protospacer-based, chimeric crRNA-tracRNA system”
From RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection (2014) · cites this paper as [16]
In the citing paper
“as mentioned in several recent publications, Cas9 tolerates mismatches between the guide RNA and target DNA in a sequence-dependent manner and potentially tolerates up to five target mismatches in human cells [12], [24], [25], [26], [27], thereby promoting undesired off-target mutations.”
From High-efficiency targeted editing of large viral genomes by RNA-guided nucleases (2014) · cites this paper as [12]
In the citing paper
“Because the sequence specificity of Streptococcus pyogenes Cas9 tolerates 4 mismatches between the gRNA and complementary sequence”
From High-efficiency targeted editing of large viral genomes by RNA-guided nucleases (2014) · cites this paper as [12]
In the citing paper
“Compared with well-known, site-specific genome editing technologies, such as ZFNs and TALENs, the new CRISPR-Cas approach is more convenient and efficient [10], [12].”
From High-efficiency targeted editing of large viral genomes by RNA-guided nucleases (2014) · cites this paper as [12]
In the citing paper
“non-specific cleavage may occur in the cellular genome [12], [24], [25], [26], [27].”
From High-efficiency targeted editing of large viral genomes by RNA-guided nucleases (2014) · cites this paper as [12]
In the citing paper
“Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 is a naturally occurring bacterial immune system that uses a novel nuclease system to protect bacteria from phage infection (6-9), and it has recently been harnessed for a variety of genome-engineering applications (10)(11)(12)(13)(14)(15)(16)(17).”
From RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection (2014) · cites this paper as [11]
In the citing paper
“In the few available publications using CRISPR/Cas9 system, the gene editing frequency is comparable with ZFN or TALEN [87].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [87]
In the citing paper
“Collectively, these studies indicate that although each base within the 20 nt guide sequence contributes to overall specificity”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [87]
In the citing paper
“As described by Zhang group [87], CRISPR/Cas 9 system can be easily employed to target multiple sites to induce a deletion of a large gene fragment.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [87]
In the citing paper
“multiple mismatches between the guide RNA and its complementary target DNA sequence can be tolerated depending on the quantity, position, and base identity of mismatches [87,90,91,93], all of which contribute to potential off-target activity.”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [87]
In the citing paper
“Moreover, no significant cytotoxicity was observed [87,88].”
From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [87]
In the citing paper
“while in December 2012 Zhang and the Broad Institute also submitted a patent application [43] simultaneously with the acceptance of Zhang’s paper on human cells’ editing for publication in Science [35].”
From CRISPR–Cas9: A History of Its Discovery and Ethical Considerations of Its Use in Genome Editing (2022) · cites this paper as [35]
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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
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Gasiunas, G., Barrangou, R., Horvath, P., & Siksnys, V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208507109 · Cited by 2,769
Mechanisms of gene silencing by double-stranded RNA
Meister, G., & Tuschl, T. (2004) · Nature · doi:10.1038/nature02873 · Cited by 2,598
CRISPR RNA Maturation by Trans-Encoded Small RNA and Host Factor RNase III
Deltcheva, E., Chylinski, K., Sharma, C. M., Gonzales, K., Chao, Y., Pirzada, Z. A., Eckert, M. R., Vogel, J., & Charpentier, E. (2011) · Nature · doi:10.1038/nature09886 · Cited by 2,563
CRISPR/Cas, the Immune System of Bacteria and Archaea
Horvath, P., & Barrangou, R. (2010) · Science · doi:10.1126/science.1179555 · Cited by 2,471
Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors
Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A., & Bonas, U. (2009) · Science · doi:10.1126/science.1178811 · Cited by 2,470
Small CRISPR RNAs Guide Antiviral Defense in Prokaryotes
Brouns, S. J. J., Jore, M. M., Lundgren, M., Westra, E. R., Slijkhuis, R. J. H., Snijders, A. P. L., Dickman, M. J., Makarova, K. S., Koonin, E. V., & van der Oost, J. (2008) · Science · doi:10.1126/science.1159689 · Cited by 2,460
The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA
Garneau, J. E., Dupuis, M.-È., Villion, M., Romero, D. A., Barrangou, R., Boyaval, P., Fremaux, C., Horvath, P., Magadán, A. H., & Moineau, S. (2010) · Nature · doi:10.1038/nature09523 · Cited by 2,336
Evolution and classification of the CRISPR–Cas systems
Makarova, K. S., Haft, D. H., Barrangou, R., Brouns, S. J. J., Charpentier, E., Horvath, P., Moineau, S., Mojica, F. J. M., Wolf, Y. I., Yakunin, A. F., et al. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2577 · Cited by 2,331
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Development of a base editor for convenient and multiplex genome editing in cyanobacteria
Li, X.-D., Liu, L.-M., Xi, Y.-C., Sun, Q.-W., Luo, Z., Huang, H.-L., Wang, X.-W., Jiang, H.-B., & Chen, W. (2024) · Communications Biology · doi:10.1038/s42003-024-06696-3 · Cited by 14
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Chromatin structure and context-dependent sequence features control prime editing efficiency
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Detection of CRISPR/Cas9-Generated off-target effect by integration-defective lentiviral vector
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Metadata
- Authors
- Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., & Zhang, F.
- Affiliations
- Broad Institute (US)
- Columbia University (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- Rockefeller University (US)
- Corresponding author
- Cong, Le
- Ran, F. Ann
- Zhang, Feng
- ORCID
- Venue
- Science
- Published
- 2013-02-15
- Volume
- 339
- Issue
- 6121
- Pages
- 819-823
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3795411
- OpenAlex
- W2064815984
- Semantic Scholar
- 51bcf2a1577b3dd876fcaa4cdf630f54d261c107
- Cited by
- 15,339
- References
- 32
- Citations by year
- 2026: 614 · 2025: 926 · 2024: 1041 · 2023: 1127 · 2022: 1311 · 2021: 1421 · 2020: 1456 · 2019: 1399 · 2018: 1464 · 2017: 1368 · 2016: 1261 · 2015: 888 · 2014: 732 · 2013: 305
- FWCI
- 476.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institute of Mental Health (DP1MH100706)
- National Cancer Institute (R01CA133404)
- National Institute of General Medical Sciences (R01GM034277, R01 GM34277, T32GM007753)
- National Institute of Allergy and Infectious Diseases (DP2AI104556)
- National Institute of Neurological Disorders and Stroke (R01NS073124)
- National Center for Chronic Disease Prevention and Health Promotion (DP1‑MH100706)
- 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, genome editing, RNA-guided DNA cleavage, nicking enzyme, homology-directed repair, single guide RNA, CRISPR arrays, human cells, mouse cells, mutagenesis
- MeSH terms
- Animals, Base Sequence, DNA, Genetic Engineering, Humans, Molecular Sequence Data, RNA, Streptococcus pyogenes, Mutagenesis, Genome, Microarray Analysis, Mice, DNA Cleavage, Inverted Repeat Sequences, Genetic Loci, Recombinational DNA Repair, CRISPR-Cas Systems
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