{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:14:36Z","timestamp":1791083676592,"version":"4.1.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:p>\n                    Neurodegeneration and cerebrovascular disease share an underlying microvascular dysfunction that may be remedied by selective transgene delivery. To date, limited options exist in which cellular components of the brain vasculature can be effectively targeted by viral vector therapeutics. In this study, we characterize the first engineered adeno-associated virus (AAV) capsid mediating high transduction of cerebral vascular pericytes and smooth muscle cells (SMCs). We performed two rounds of\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    selection with an AAV capsid scaffold displaying a heptamer peptide library to isolate capsids that traffic to the brain after intravenous delivery. One identified capsid, termed AAV-PR, demonstrated high transduction of the brain vasculature, in contrast to the parental capsid, AAV9, which transduces mainly neurons and astrocytes. Further analysis using tissue clearing, volumetric rendering, and colocalization revealed that AAV-PR enabled high transduction of cerebral pericytes located on small-caliber vessels and SMCs in the larger arterioles and penetrating pial arteries. Analysis of tissues in the periphery indicated that AAV-PR also transduced SMCs in large vessels associated with the systemic vasculature. AAV-PR was also able to transduce primary human brain pericytes with higher efficiency than AAV9. Compared with previously published AAV capsids tropisms, AAV-PR represents the first capsid to allow for effective transduction of brain pericytes and SMCs and offers the possibility of genetically modulating these cell types in the context of neurodegeneration and other neurological diseases.\n                  <\/jats:p>","DOI":"10.1089\/hum.2022.211","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T01:56:16Z","timestamp":1687917376000},"page":"682-696","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["An Engineered Adeno-Associated Virus Capsid Mediates Efficient Transduction of Pericytes and Smooth Muscle Cells of the Brain Vasculature"],"prefix":"10.1177","volume":"34","author":[{"given":"Servio H.","family":"Ramirez","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA."},{"name":"Shriners Hospitals Pediatric Research Center, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan F.","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA."},{"name":"Shriners Hospitals Pediatric Research Center, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siobhan","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian L.","family":"Lino Cardenas","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Cardiology; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpani N. Udeni Galpayage","family":"Dona","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA."},{"name":"Shriners Hospitals Pediatric Research Center, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Killian S.","family":"Hanlon","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Neurology; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise","family":"Hudry","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Neurology; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demitri De La","family":"Cruz","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Neurology; Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Ng","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Neurology; Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabyasachi","family":"Das","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane M.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology; Massachusetts General Hospital, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josette","family":"Nammour","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Neurology; 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