{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:37:03Z","timestamp":1787020623147,"version":"build-2736575974"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"S8","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T00:00:00Z","timestamp":1600387200000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Single nucleotide variants account for approximately 90% of all known pathogenic variants responsible for human diseases. Recently discovered CRISPR\/Cas9 base editors can correct individual nucleotides without cutting DNA and inducing double-stranded breaks. We aimed to find all possible pathogenic variants which can be efficiently targeted by any of the currently described base editors and to present them for further selection and development of targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>ClinVar database (GRCh37_clinvar_20171203) was used to search and select mutations available for current single-base editing systems. We included only pathogenic and likely pathogenic variants for further analysis. For every potentially editable mutation we checked the presence of PAM. If a PAM was found, we analyzed the sequence to find possibility to edit only one nucleotide without changing neighboring nucleotides. The code of the script to search Clinvar database and to analyze the sequences was written in R and is available in the appendix.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 21 editing system currently reported in 9 publications. Every system has different working characteristics such as the editing window and PAM sequence. C\u2009&gt;\u2009T base editors can precisely target 3196 mutations (46% of all pathogenic T\u2009&gt;\u2009C variants), and A\u2009&gt;\u2009G editors \u2013 6900 mutations (34% of all pathogenic G\u2009&gt;\u2009A variants).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Protein engineering helps to develop new enzymes with a narrower window of base editors as well as using new Cas9 enzymes with different PAM sequences. But, even now the list of mutations which can be targeted with currently available systems is huge enough to choose and develop new targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-020-00735-8","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T02:03:52Z","timestamp":1600394632000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genome scale analysis of pathogenic variants targetable for single base editing"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4962-6947","authenticated-orcid":false,"given":"Alexander V.","family":"Lavrov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgi G.","family":"Varenikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail Yu","family":"Skoblov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,18]]},"reference":[{"key":"735_CR1","unstructured":"Online Mendelian Inheritance in Man, OMIM\u00ae: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD); 2019. https:\/\/omim.org\/ Accessed 15 Jan 2019."},{"key":"735_CR2","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1093\/nar\/gkx1153","volume":"46","author":"MJ Landrum","year":"2018","unstructured":"Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46:1062\u20137.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"735_CR3","doi-asserted-by":"publisher","first-page":"eaap9004","DOI":"10.1126\/sciadv.aap9004","volume":"4","author":"C Long","year":"2018","unstructured":"Long C, Li H, Tiburcy M, Rodriguez-Caycedo C, Kyrychenko V, Zhou H, Zhang Y, et al. Correction of diverse muscular dystrophy mutations in human engineered heart muscle by single-site genome editing. Sci Adv. 2018;4(1):eaap9004.","journal-title":"Sci Adv"},{"key":"735_CR4","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/nbt.4192","volume":"36","author":"M Kosicki","year":"2018","unstructured":"Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR\u2013Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018;36:765\u201371.","journal-title":"Nat Biotechnol"},{"key":"735_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1093\/hmg\/ddy120","volume":"27","author":"C Zhang","year":"2018","unstructured":"Zhang C, Quan R, Wang J. Development and application of CRISPR\/Cas9 technologies in genomic editing. Hum Mol Genet. 2018;27:79\u201388.","journal-title":"Hum Mol Genet"},{"key":"735_CR6","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nature17946","volume":"533","author":"AC Komor","year":"2016","unstructured":"Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533:420\u20134.","journal-title":"Nature."},{"key":"735_CR7","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nbt.3803","volume":"35","author":"YB Kim","year":"2017","unstructured":"Kim YB, Komor AC, Levy JM, Packer MS, Zhao KT, Liu DR. Increasing the genome-targeting scope and precision of base editing with engineered Cas9-cytidine deaminase fusions. Nat Biotechnol. 2017;35:371\u20136.","journal-title":"Nat Biotechnol"},{"key":"735_CR8","doi-asserted-by":"publisher","first-page":"aaf8729","DOI":"10.1126\/science.aaf8729","volume":"353","author":"K Nishida","year":"2016","unstructured":"Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M, et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science. 2016;353:aaf8729.","journal-title":"Science."},{"issue":"8","key":"735_CR9","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/s41422-018-0052-4","volume":"28","author":"W Jiang","year":"2018","unstructured":"Jiang W, Feng S, Huang S, Yu W, Li G, Yang G, et al. BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity. Cell Res. 2018;28(8):855\u201361.","journal-title":"Cell Res"},{"issue":"7699","key":"735_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature26155","volume":"556","author":"JH Hu","year":"2018","unstructured":"Hu JH, Miller SM, Geurts MH, Tang W, Chen L, Sun N, et al. Evolved Cas9 variants with broad PAM compatibility and high DNA specificity. Nature. 2018;556(7699):57\u201363.","journal-title":"Nature."},{"key":"735_CR11","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1038\/nbt.4102","volume":"7","author":"X Li","year":"2018","unstructured":"Li X, Wang Y, Liu Y, Yang B, Wang X, Wei J, et al. Base editing with a Cpf1-cytidine deaminase fusion. Nat Biotechnol. 2018;7:324\u20137.","journal-title":"Nat Biotechnol"},{"issue":"10","key":"735_CR12","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/nbt.4199","volume":"36","author":"JM Gehrke","year":"2018","unstructured":"Gehrke JM, Cervantes O, Clement MK, Wu Y, Zeng J, Bauer DE, et al. An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat Biotechnol. 2018;36(10):977\u201382.","journal-title":"Nat Biotechnol"},{"key":"735_CR13","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/s41467-018-08034-8","volume":"10","author":"J Tan","year":"2019","unstructured":"Tan J, Zhang F, Karcher D, Bock R. Engineering of high-precision base editors for site-specific single nucleotide replacement. Nat Commun. 2019;10:439.","journal-title":"Nat Commun"},{"key":"735_CR14","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nature24644","volume":"551","author":"NM Gaudelli","year":"2017","unstructured":"Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, et al. Programmable base editing of a\u2022T to G\u2022C in genomic DNA without DNA cleavage. Nature. 2017;551:464\u201371.","journal-title":"Nature."}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00735-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-020-00735-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00735-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T19:21:10Z","timestamp":1631906470000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-020-00735-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":14,"journal-issue":{"issue":"S8","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["735"],"URL":"https:\/\/doi.org\/10.1186\/s12920-020-00735-8","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"13 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"80"}}