{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:05:08Z","timestamp":1790107508225,"version":"4.0.1"},"reference-count":43,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["The CRISPR Journal"],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:p>\n                    Alzheimer's disease (AD) is the result of abnormal processing of the amyloid precursor protein (APP) by \u03b2-secretase and \u03b3-secretase, which leads to the formation of toxic \u03b2-amyloid peptides. The toxic \u03b2-amyloid peptides induce neuron death, memory problems, and AD development. Several\n                    <jats:italic toggle=\"yes\">APP<\/jats:italic>\n                    mutations increase the risk of developing early-onset AD. However, the A673T mutation identified in the Icelandic population prevents AD development by reducing the cleavage of APP by \u03b2-secretase. In this study, we inserted the A673T mutation in human cells using the CRISPR prime editing (PE) technique. Repeated PE treatments resulted in the insertion of the A673T mutation in up to 49.2% of\n                    <jats:italic toggle=\"yes\">APP<\/jats:italic>\n                    genes when a second nick was induced in the other DNA strand. When the protospacer adjacent motif used for PE was also mutated, up to 68.9% of the\n                    <jats:italic toggle=\"yes\">APP<\/jats:italic>\n                    genes contained the protective A673T mutation. PE is a promising approach to introduce the A673T mutation precisely without mutating nearby nucleotides.\n                  <\/jats:p>","DOI":"10.1089\/crispr.2021.0085","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T13:42:00Z","timestamp":1644327720000},"page":"109-122","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Insertion of the Icelandic Mutation (A673T) by Prime Editing: A Potential Preventive Treatment for Familial and Sporadic Alzheimer's Disease"],"prefix":"10.1177","volume":"5","author":[{"given":"Guillaume","family":"Tremblay","sequence":"first","affiliation":[{"name":"Research Center of CHU de Qu\u00e9bec-Universit\u00e9 Laval, Department of Molecular Medicine, Laval University, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Research Center of CHU de Qu\u00e9bec-Universit\u00e9 Laval, Department of Molecular Medicine, Laval University, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric Happi","family":"Mbakam","sequence":"additional","affiliation":[{"name":"Research Center of CHU de Qu\u00e9bec-Universit\u00e9 Laval, Department of Molecular Medicine, Laval University, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques P.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Research Center of CHU de Qu\u00e9bec-Universit\u00e9 Laval, Department of Molecular Medicine, Laval University, Quebec, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0909142"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2021.01061"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14122"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005777"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-12-1612"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.09.018"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14726"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.04.002"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-385883-2.00008-4"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.755264"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168979"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002270"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11283"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2012.09.017"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2015.07.011"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-021-02385-y"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.599027"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24969"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.744722"},{"key":"e_1_3_5_22_2","article-title":"Protective A673T mutation decreases amyloid-beta peptide production for a majority of APP genes containing a mutation responsible for a Familial Alzheimer Disease","author":"Guyon A","year":"2020","unstructured":"Guyon A, , Rousseau J, , Bertin T, et al. 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