{"id":19824,"date":"2024-12-13T12:00:00","date_gmt":"2024-12-13T11:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2024\/12\/13\/prime-editor-gene-therapy-and-trex1-mosaicism-in-retinal-vasculopathy-with-cerebral-leukoencephalopathy\/"},"modified":"2024-12-13T12:00:00","modified_gmt":"2024-12-13T11:00:00","slug":"prime-editor-gene-therapy-and-trex1-mosaicism-in-retinal-vasculopathy-with-cerebral-leukoencephalopathy","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2024\/12\/13\/prime-editor-gene-therapy-and-trex1-mosaicism-in-retinal-vasculopathy-with-cerebral-leukoencephalopathy\/","title":{"rendered":"Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy"},"content":{"rendered":"<div>\n<p>J Clin Immunol. 2024 Dec 13;45(1):54. doi: 10.1007\/s10875-024-01846-y.<\/p>\n<p>ABSTRACT<\/p>\n<p>TREX1 mutations underlie a variety of human diseases, including retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S), a catastrophic adult-onset vasculopathy that is often confused with multiple sclerosis, systemic vasculitis, or systemic lupus erythematosus. Patients with RVCL develop brain, retinal, liver, and kidney disease around age 35-55, leading to premature death in 100% of patients expressing an autosomal dominant C-terminally truncated form of TREX1. We previously demonstrated that RVCL is characterized by high levels of DNA damage, premature cellular senescence, and risk of early-onset breast cancer before age 45. Here, we report human TREX1 mosaicism causing organ-limited RVCL in the retina, as well as a gene therapy to synthetically create TREX1 mosaicism as a potential treatment for RVCL. In our patient with organ-limited disease, the mosaic TREX1 mutant allele underwent germline transmission to 3 children, who developed severe multi-organ disease at ~ age 40, unlike their mosaic parent, who has organ-limited disease at age 74. Additionally, we describe our TREX1 prime editor gene therapy that corrects the most common RVCL-causing TREX1 variant in cell culture and in mice. Thus, TREX1 mosaicism causes organ-limited RVCL with a normal lifespan, suggesting that a gene therapy to create TREX1 mosaicism in adults may someday become useful as a treatment for patients with RVCL.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39671052\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_campaign=journals&amp;utm_content=8102137&amp;ff=20241213133624&amp;v=2.18.0.post9+e462414\">39671052<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1007\/s10875-024-01846-y\">10.1007\/s10875-024-01846-y<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Clin Immunol. 2024 Dec 13;45(1):54. doi: 10.1007\/s10875-024-01846-y. ABSTRACT TREX1 mutations underlie a variety of human diseases, including retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S), a catastrophic adult-onset vasculopathy that is often confused with multiple sclerosis, systemic vasculitis, or systemic lupus erythematosus. Patients with RVCL develop brain, retinal, liver, and kidney disease around age &#8230; <a title=\"Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2024\/12\/13\/prime-editor-gene-therapy-and-trex1-mosaicism-in-retinal-vasculopathy-with-cerebral-leukoencephalopathy\/\" aria-label=\"Read more about Prime Editor Gene Therapy and TREX1 Mosaicism in Retinal Vasculopathy with Cerebral Leukoencephalopathy\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[69,42],"tags":[],"class_list":["post-19824","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19824","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=19824"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/19824\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=19824"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=19824"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=19824"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}