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We have recently demonstrated that a long non\u2010coding RNA, <jats:italic>Neat1<\/jats:italic> as a primary regulator of matrix metalloproteinase (MMP) 3 and MMP13 activity, and its induction in the target joint has a deteriorating effect on articular cartilage. In the present study, we administered an Adeno\u2010associated virus (AAV) 5 vector carrying an short hairpin (sh)RNA to <jats:italic>Neat1<\/jats:italic> via intra\u2010articular injection alone or in conjunction with systemic administration of a capsid\u2010modified AAV8 (K31Q) vector carrying F8 gene (F8\u2010BDD\u2010V3) to study its impact on HA. AAV8K31Q\u2010F8 vector administration at low dose, led to an increase in FVIII activity (16%\u201328%) in treated mice. We further observed a significant knockdown of <jats:italic>Neat1<\/jats:italic> (~40 fold vs. untreated injured joint, <jats:italic>p<\/jats:italic>\u2009=\u20090.005) in joint tissue of treated mice and a downregulation of chondrodegenerative enzymes, MMP3, MMP13 and the inflammatory mediator\u2010 cPLA2, in mice receiving combination therapy. These data demonstrate that AAV mediated <jats:italic>Neat1<\/jats:italic> knockdown in combination with F8 gene augmentation can potentially impact mediators of haemophilic joint disease.<\/jats:p>","DOI":"10.1111\/jcmm.18460","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T13:24:55Z","timestamp":1718198695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>AAV<\/scp> mediated repression of Neat1 <scp>lncRNA<\/scp> combined with <scp>F8<\/scp> gene augmentation mitigates pathological mediators of joint disease in haemophilia"],"prefix":"10.1111","volume":"28","author":[{"given":"Pratiksha","family":"Sarangi","sequence":"first","affiliation":[{"name":"Laurus Center for Gene Therapy, Department of Biological Sciences and Bioengineering and Mehta Family Centre for Engineering in Medicine and Gangwal School of Medical Sciences and Technology Indian Institute of Technology 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