{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:40:20Z","timestamp":1791589220089,"version":"4.3.4"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:p>\n                    Dietary deficiencies in essential micronutrients and other phytonutrients represent a global health and economic burden, contributing to \u201chidden hunger\u201d and chronic diseases. While genome editing has been employed to improve individual nutritional traits in crops, multibiofortification through simultaneous modification of multiple distinct metabolic pathways is more challenging. Here, we designed a multiplex CRISPR-Cas strategy to edit five key genes in tomato:\n                    <jats:italic toggle=\"yes\">Sl7-DR2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SlGAD3<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SlSGR1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SlGGP1<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">SlGGP2<\/jats:italic>\n                    . This approach successfully generated quintuple mutant (\n                    <jats:italic toggle=\"yes\">5m<\/jats:italic>\n                    ) tomato lines simultaneously biofortified with seven health-promoting compounds: vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    (from 0 to 0.70 \u03bcg\/g dry weight), vitamin C (up to 2.53-fold), provitamin A\/\u03b2-carotene (up to 3.86-fold), \u03b1-carotene (up to 2.47-fold), lutein (up to 3.26-fold), lycopene (up to 7.07-fold), and \u03b3-aminobutyric acid (GABA, up to 5.26-fold). Notably, these multibiofortified tomatoes exhibited no significant trade-offs in plant growth or fruit quality. Extracts from\n                    <jats:italic toggle=\"yes\">5m<\/jats:italic>\n                    tomatoes showed enhanced suppression of colorectal cancer cell proliferation in vitro. This antiproliferative effect was validated in vivo, where dietary supplementation with\n                    <jats:italic toggle=\"yes\">5m<\/jats:italic>\n                    tomato powder significantly inhibited tumor growth in a mouse xenograft model. Our work demonstrates an effective strategy for developing a next generation of \u201cfunctional foods\u201d through multibiofortification, creating a single, nutrient-dense crop that combats both micronutrient malnutrition and chronic diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2603937123","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T17:47:15Z","timestamp":1779904035000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Multiplex gene editing enables the multibiofortification of essential vitamins and other health-promoting phytonutrients in tomato"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8406-0948","authenticated-orcid":false,"given":"Yechun","family":"Hong","sequence":"first","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2571-956X","authenticated-orcid":false,"given":"Zongjun","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialei","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5301-1673","authenticated-orcid":false,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Anhui Agricultural University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaobo","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xuan","family":"Lyu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengpeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-731X","authenticated-orcid":false,"given":"Jian-Kang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Advanced Biotechnology, Institute of Homeostatic Medicine, and School of Medicine, Southern University of Science and Technology","place":["Shenzhen, China"]},{"name":"Faculty of Medicine, Macau University of Science and Technology","place":["Macau SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1159\/000371618"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00276-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.37"},{"key":"e_1_3_4_4_2","first-page":"439","volume-title":"Developmental Science and Sustainable Development Goals for Children and Youth","author":"U. 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