The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index.
Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
Open accessAbstract
A PAMless base editor: CRISPR-Cas DNA base editing typically requires a specific motif for targeting known as a protospacer-adjacent motif (PAM). This requirement limits the sequences within a genome that can be targeted. Walton et al. engineered specific variants of the Streptococcus pyogenes Cas9 enzyme named SpG and SpRY that could recognize and edit a wider array of PAMs. Using SpRY, the authors were able to correct previously uneditable mutations associated with human disease. Although off-target effects were observed for these engineered Cas enzymes at levels similar to those of the wild-type enzyme, depending on the context, these engineered enzymes widen the potential applications of precision genome editing. Science , this issue p. 290
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“Efforts are ongoing to develop PAM-free Cas9 molecules to eliminate PAM site constraints altogether, thereby increasing the flexibility and effectiveness of genome editingthrough structure-based rational engineering or by altering amino acid substitutions in the PAM-interacting domain (Walton et al., 2020).”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Walton et al., 2020
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
“CRISPR-Cas dominates the field because of the ease of using guide RNAs directing the CRISPR complex to specific DNA sequences and the increasing ability to target most sites in the genome.121,122”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [122]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Building on this, Walton et al. (2020) introduced the SpG variant, which can recognize a broader range of NGN PAMs.”
From Emerging applications of gene editing technologies for the development of climate-resilient crops (2025) · cites this paper as Walton et al., 2020
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In the citing paper
“These can be targeted in combination with evolved Cas9 variants such as SpCas9-NG20 or SpG.19”
From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [19]
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“These can be targeted with SpRY.19”
From Protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools (2024) · cites this paper as [19]
The cited source says what the claim attributes to it.
In the citing paper
“Cas9 genomic localization is delimited by the protospacer adjacent motif (PAM), which is NGG for SpCas9 while evolved variants of SpCas9 tolerate a broader range of PAM sequences17–21.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [21]
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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
Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage
Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., & Liu, D. R. (2016) · Nature · doi:10.1038/nature17946 · Cited by 5,437
Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System
Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., Essletzbichler, P., Volz, S. E., Joung, J., van der Oost, J., Regev, A., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.038 · Cited by 4,761
Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage
Gaudelli, N. M., Komor, A. C., Rees, H. A., Packer, M. S., Badran, A. H., Bryson, D. I., & Liu, D. R. (2017) · Nature · doi:10.1038/nature24644 · Cited by 4,184
High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects
Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., & Joung, J. K. (2016) · Nature · doi:10.1038/nature16526 · Cited by 2,673
Self-citationRNA-guided editing of bacterial genomes using CRISPR-Cas systems
Jiang, W., Bikard, D., Cox, D., Zhang, F., & Marraffini, L. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2508 · Cited by 2,429
Rationally engineered Cas9 nucleases with improved specificity
Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., & Zhang, F. (2016) · Science · doi:10.1126/science.aad5227 · Cited by 2,414
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases
Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) · Nature Biotechnology · doi:10.1038/nbt.3117 · Cited by 2,268
DNA interrogation by the CRISPR RNA-guided endonuclease Cas9
Sternberg, S. H., Redding, S., Jinek, M., Greene, E. C., & Doudna, J. A. (2014) · Nature · doi:10.1038/nature13011 · Cited by 1,822
Base editing: precision chemistry on the genome and transcriptome of living cells
Rees, H. A., & Liu, D. R. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0059-1 · Cited by 1,675
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CRISPR mediated genome editing, a tool to dissect RNA modification processes
Pickerill, E. S., & Bernstein, D. A. (2021) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2021.06.013 · Cited by 1
Applications of CRISPR-Cas System in Tumor Biology
Ma, M., Liu, Y., & Huang, W. (2021) · ONCOLOGIE · doi:10.32604/oncologie.2022.019415 · Cited by 1
Metadata
- Authors
- Walton, R. T., Christie, K. A., Whittaker, M. N., & Kleinstiver, B. P.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- Kleinstiver, Benjamin P.
- Venue
- Science
- Published
- 2020-04-17
- Volume
- 368
- Issue
- 6488
- Pages
- 290-296
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7297043
- OpenAlex
- W3013504322
- Semantic Scholar
- 84609b61a82a11e3122a81b5bdae20a2822e577b
- Cited by
- 1,233
- References
- 48
- Citations by year
- 2026: 157 · 2025: 200 · 2024: 190 · 2023: 213 · 2022: 203 · 2021: 177 · 2020: 93
- FWCI
- 56.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01-HL142494)
- National Cancer Institute (R00-CA218870)
- American Society of Gene and Cell Therapy
- Margaret Q. Landenberger Research Foundation
- 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, SpCas9, SPG, SpRY, base editing, genome editing, human cells
- MeSH terms
- Protein Domains, Gene Editing, CRISPR-Associated Protein 9, Humans, Substrate Specificity, Mutagenesis, Gene Targeting, Genetic Predisposition to Disease, HEK293 Cells, CRISPR-Cas Systems
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