Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-021-24849-4
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dc.titleDisrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy
dc.contributor.authorChai, Ruth Jinfen
dc.contributor.authorWerner, Hendrikje
dc.contributor.authorLi, Peter Yiqing
dc.contributor.authorLee, Yin Loon
dc.contributor.authorKhaing Thet Nyein
dc.contributor.authorSolovei, Irina
dc.contributor.authorTuan Danh Anh Luu
dc.contributor.authorSharma, Bhavya
dc.contributor.authorNavasankari, Raju
dc.contributor.authorMaric, Martina
dc.contributor.authorSim, Lois Yu En
dc.contributor.authorLoh, Ying Jie
dc.contributor.authorAliwarga, Edita
dc.contributor.authorCheong, Jason Wen Long
dc.contributor.authorChojnowski, Alexandre
dc.contributor.authorAutio, Matias Ilmari
dc.contributor.authorHaiyang, Yu
dc.contributor.authorBoon Tan, Kenneth Kian
dc.contributor.authorKeng, Choong Tat
dc.contributor.authorNg, Shi Ling
dc.contributor.authorChew, Wei Leong
dc.contributor.authorFerenczi, Michael
dc.contributor.authorBurke, Brian
dc.contributor.authorFoo, Roger Sik Yin
dc.contributor.authorStewart, Colin L.
dc.date.accessioned2022-10-26T09:02:33Z
dc.date.available2022-10-26T09:02:33Z
dc.date.issued2021-08-05
dc.identifier.citationChai, Ruth Jinfen, Werner, Hendrikje, Li, Peter Yiqing, Lee, Yin Loon, Khaing Thet Nyein, Solovei, Irina, Tuan Danh Anh Luu, Sharma, Bhavya, Navasankari, Raju, Maric, Martina, Sim, Lois Yu En, Loh, Ying Jie, Aliwarga, Edita, Cheong, Jason Wen Long, Chojnowski, Alexandre, Autio, Matias Ilmari, Haiyang, Yu, Boon Tan, Kenneth Kian, Keng, Choong Tat, Ng, Shi Ling, Chew, Wei Leong, Ferenczi, Michael, Burke, Brian, Foo, Roger Sik Yin, Stewart, Colin L. (2021-08-05). Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy. Nature Communications 12 (1) : 4722. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-021-24849-4
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/233560
dc.description.abstractMutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3–4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1’s function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450. © 2021, The Author(s).
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2021
dc.typeArticle
dc.contributor.departmentMEDICINE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.description.doi10.1038/s41467-021-24849-4
dc.description.sourcetitleNature Communications
dc.description.volume12
dc.description.issue1
dc.description.page4722
dc.published.statePublished
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