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To improve understanding of the roles of endothelial cells (ECs) in health and disease, EC-specific genome editing technologies have been developed in recent years. Therapeutic strategies that aim to restore a healthy endothelial monolayer include the inhibition of endothelial genes that cause EC injury and dysfunction and the induction or activation of endothelial genes that drive EC repair and regeneration. In this review, we describe established recombinase-mediated genetic modification technologies and emerging EC-specific genome editing technologies including viral and non-viral delivery of the CRISPR\/Cas9 genome editing system, and we summarize the strengths and limitations of each technology. We then discuss possible avenues for future research, including the development of organ-specific EC genome editing technologies. In short, EC-specific genome editing technologies can be used to modulate gene expression selectively in ECs and even within a specific vascular bed and\/or distinctive EC subtype, and, in doing so, greatly improve the understanding of vascular biology and help develop precision genetic medicine targeting the disease-causing vascular bed(s) to effectively treat diseases caused by vascular endothelial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms27115100","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"5100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Contemporary Endothelial Genome Editing Technologies: Towards Precision Genetic Medicine for Vascular Diseases"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-0339","authenticated-orcid":false,"given":"You-Yang","family":"Zhao","sequence":"first","affiliation":[{"name":"Program for Lung and Vascular Biology, Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"},{"name":"Genetic Medicine and Nanotechnology Development Center (GeneMeNDer), Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Departments of Pharmacology and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"},{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin E.","family":"Evans","sequence":"additional","affiliation":[{"name":"Program for Lung and Vascular Biology, Section for Injury Repair and Regeneration Research, Stanley Manne Children\u2019s Research Institute, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL 60611, USA"},{"name":"Department of Pediatrics, Division of Critical Care, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","first-page":"3527","article-title":"Endothelial cells in physiology and in the pathophysiology of vascular disorders","volume":"91","author":"Cines","year":"1998","journal-title":"Blood"},{"key":"ref_2","first-page":"139","article-title":"Endothelium in health and disease","volume":"60","author":"Aird","year":"2008","journal-title":"Pharmacol. 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