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The primary cause of death is a heart attack or stroke arising from atherosclerosis. A characteristic feature of HGPS arteries is loss of smooth muscle cells. An adenine base editor (ABE7.10max) corrected the point mutation and produced significant improvement in HGPS mouse lifespan, vascular smooth muscle cell density, and adventitial fibrosis. To assess whether base editing correction of human HGPS tissue engineered blood vessels (TEBVs) prevents the HGPS vascular phenotype and to identify the minimum fraction of edited smooth muscle cells needed to effect such changes, we transduced HGPS iPSCs with lentivirus containing ABE7.10max. Endothelial cells (viECs) and smooth muscle cells (viSMCs) obtained by differentiation of edited HGPS iPSCs did not express progerin and had double-stranded DNA breaks and reactive oxygen species at the same levels as healthy viSMCs and viECs. Editing HGPSviECs restored a normal response to shear stress. Normal vasodilation and viSMC density were restored in TEBVs made with edited cells. When TEBVs were prepared with at least 50% edited smooth muscle cells, viSMC proliferation and myosin heavy chain levels significantly improved. Sequencing of TEBV cells after perfusion indicated an enrichment of edited cells after 5\u2009weeks of perfusion when they comprised 50% of the initial number of cells in the TEBVs. Thus, base editing correction of a fraction of HGPS vascular cells improves human TEBV phenotype.<\/jats:p>","DOI":"10.1063\/5.0244026","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T09:01:17Z","timestamp":1740560477000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Adenine base editing rescues pathogenic phenotypes in tissue engineered vascular model of Hutchinson-Gilford progeria syndrome"],"prefix":"10.1063","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0995-5730","authenticated-orcid":false,"given":"Nadia O.","family":"Abutaleb","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Duke University 1 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2917-2060","authenticated-orcid":false,"given":"Xin D.","family":"Gao","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard 2 , Cambridge, Massachusetts 02142,","place":["USA"]},{"name":"Department of Chemistry and Chemical Biology, Harvard University 3 , Cambridge, Massachusetts 02138,","place":["USA"]},{"name":"Howard Hughes Medical Institute, Harvard University 4 , Cambridge, Massachusetts 02138,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8008-5822","authenticated-orcid":false,"given":"Akhil","family":"Bedapudi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University 1 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8965-9896","authenticated-orcid":false,"given":"Leandro","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University 1 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6205-8318","authenticated-orcid":false,"given":"Kevin L.","family":"Shores","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University 1 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3405-3381","authenticated-orcid":false,"given":"Crystal","family":"Kennedy","sequence":"additional","affiliation":[{"name":"University Program in Genetics and Genomics, Duke University 5 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2638-2946","authenticated-orcid":false,"given":"Jordyn E.","family":"Duby","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard 2 , Cambridge, Massachusetts 02142,","place":["USA"]},{"name":"Department of Chemistry and Chemical Biology, Harvard University 3 , Cambridge, Massachusetts 02138,","place":["USA"]},{"name":"Howard Hughes Medical Institute, Harvard University 4 , Cambridge, Massachusetts 02138,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5806-2939","authenticated-orcid":false,"given":"Kan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Molecular Genetics, University of Maryland 6 , College Park, Maryland 20742,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-7557","authenticated-orcid":false,"given":"David R.","family":"Liu","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard 2 , Cambridge, Massachusetts 02142,","place":["USA"]},{"name":"Department of Chemistry and Chemical Biology, Harvard University 3 , Cambridge, Massachusetts 02138,","place":["USA"]},{"name":"Howard Hughes Medical Institute, Harvard University 4 , Cambridge, Massachusetts 02138,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6885-4489","authenticated-orcid":false,"given":"George A.","family":"Truskey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University 1 , Durham, North Carolina 27708,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"317","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"2025022614011271000_c1","first-page":"249","article-title":"Chapter 18 - 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