{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:55:32Z","timestamp":1790574932728,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["NHGRI HG200305"],"award-info":[{"award-number":["NHGRI HG200305"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hutchinson\u2010Gilford progeria syndrome (HGPS) is a premature aging disorder affecting tissues of mesenchymal origin. Most patients harbor a c.1824C&gt;T\/p.G608= variant, commonly described as G608G, in exon 11 of\n                    <jats:italic>LMNA<\/jats:italic>\n                    that leads to aberrant splicing and production of the toxic progerin protein. In addition to cardiovascular, dermal, and adipose tissue deterioration, HGPS mouse models also develop progressive bone dysplasia that occurs in patients. Here we characterize the efficacy of in\u00a0vivo mutation correction with an adenine base editor (ABE) to rescue structural and functional defects in HGPS transgenic murine bone tissue. Treatment of double\u2010copy transgenic osteoblast cultures with a lentiviral\u2010delivered CRISPR\u2010Cas9 ABE achieved nearly 40% gene correction in\u00a0vitro, resulting in significant reduction of progerin transcripts and protein, in the absence of selective agents. Furthermore, gene correction improved progeroid osteoblasts' capacity to deposit and mineralize extracellular matrix compared to untreated cultures. In\u00a0vivo, a single intravenous dose of AAV9\u2010delivered ABE corrected the mutation, achieving ~14%, ~22%, ~10% and &lt;\u20091% correction in bone by six months of age when administered at P3, P14, 1 and 4\u2009months of age, respectively. Partially rescued bone structural and physical parameters were observed in P14\u2010treated mice with concomitant normalization of gene transcriptional programs and intracellular signaling pathways involved in bone remodeling. This work demonstrates in\u00a0vivo delivery of a locus\u2010specific DNA base editor to bone tissue, delineates the timing of treatment required for maximum efficacy, and suggests that this system might be tailored for application to other monogenic bone disorders.\n                  <\/jats:p>","DOI":"10.1111\/acel.70700","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:27:38Z","timestamp":1788431258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vivo Base Editing Partially Rescues Bone Dysplasia in a Mouse Model of Hutchinson\u2010Gilford Progeria Syndrome"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-5289","authenticated-orcid":false,"given":"Wayne A.","family":"Cabral","sequence":"first","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"},{"name":"Skeletal Mechanobiology Laboratory National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb M.","family":"Grenko","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Yeritsyan","sequence":"additional","affiliation":[{"name":"Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopedic Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indeevar","family":"Beeram","sequence":"additional","affiliation":[{"name":"Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopedic Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Laiwala","sequence":"additional","affiliation":[{"name":"Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopedic Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2577-5377","authenticated-orcid":false,"given":"Urraca L.","family":"Tavarez","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingfen","family":"Yan","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Wincovitch","sequence":"additional","affiliation":[{"name":"Advanced Imaging and Analysis Core Facility National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke W.","family":"Koblan","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare Broad Institute of Harvard and MIT  Cambridge Massachusetts USA"},{"name":"Department of Chemistry and Chemical Biology Harvard University  Cambridge Massachusetts USA"},{"name":"Howard Hughes Medical Institute Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin D.","family":"Gao","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare Broad Institute of Harvard and MIT  Cambridge Massachusetts USA"},{"name":"Department of Chemistry and Chemical Biology Harvard University  Cambridge Massachusetts USA"},{"name":"Howard Hughes Medical Institute Harvard University  Cambridge Massachusetts USA"},{"name":"Department of Ophthalmology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirui","family":"An","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare Broad Institute of Harvard and MIT  Cambridge Massachusetts USA"},{"name":"Department of Chemistry and Chemical Biology Harvard University  Cambridge Massachusetts USA"},{"name":"Howard Hughes Medical Institute Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narisu","family":"Narisu","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0197-3811","authenticated-orcid":false,"given":"Leslie G.","family":"Biesecker","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Liu","sequence":"additional","affiliation":[{"name":"Merkin Institute of Transformative Technologies in Healthcare Broad Institute of Harvard and MIT  Cambridge Massachusetts USA"},{"name":"Department of Chemistry and Chemical Biology Harvard University  Cambridge Massachusetts USA"},{"name":"Howard Hughes Medical Institute Harvard University  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-3489","authenticated-orcid":false,"given":"Ara","family":"Nazarian","sequence":"additional","affiliation":[{"name":"Musculoskeletal Translational Innovation Initiative, Carl J. Shapiro Department of Orthopedic Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Collins","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland USA"},{"name":"The Progeria Research Foundation  Peabody Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6603-1833","authenticated-orcid":false,"given":"Michael R.","family":"Erdos","sequence":"additional","affiliation":[{"name":"Molecular Genetics Section, Center for Precision Health Research National Human Genome Research Institute, NIH  Bethesda Maryland 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