{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Esposito F"],"funding":["European Research Council","Telethon"],"pagination":["e15199"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9174883"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(6)"],"pubmed_abstract":["Liver gene therapy with adeno-associated viral (AAV) vectors is under clinical investigation for haemophilia A (HemA), the most common inherited X-linked bleeding disorder. Major limitations are the large size of the F8 transgene, which makes packaging in a single AAV vector a challenge, as well as the development of circulating anti-F8 antibodies which neutralise F8 activity. Taking advantage of split-intein-mediated protein trans-splicing, we divided the coding sequence of the large and highly secreted F8-N6 variant in two separate AAV-intein vectors whose co-administration to HemA mice results in the expression of therapeutic levels of F8 over time. This occurred without eliciting circulating anti-F8 antibodies unlike animals treated with the single oversized AAV-F8 vector under clinica"],"journal":["EMBO molecular medicine"],"pubmed_title":["Liver gene therapy with intein-mediated F8 trans-splicing corrects mouse haemophilia A."],"pmcid":["PMC9174883"],"funding_grant_id":["694323","TGM16MT1"],"pubmed_authors":["Tornabene P","Follenzi A","Lyubenova H","Auricchio S","Nusco E","Merlin S","Esposito F","Manni G","Olgasi C","Gargaro M","Fallarino F","Auricchio A","Iuliano A"],"additional_accession":[]},"is_claimable":false,"name":"Liver gene therapy with intein-mediated F8 trans-splicing corrects mouse haemophilia A.","description":"Liver gene therapy with adeno-associated viral (AAV) vectors is under clinical investigation for haemophilia A (HemA), the most common inherited X-linked bleeding disorder. Major limitations are the large size of the F8 transgene, which makes packaging in a single AAV vector a challenge, as well as the development of circulating anti-F8 antibodies which neutralise F8 activity. Taking advantage of split-intein-mediated protein trans-splicing, we divided the coding sequence of the large and highly secreted F8-N6 variant in two separate AAV-intein vectors whose co-administration to HemA mice results in the expression of therapeutic levels of F8 over time. This occurred without eliciting circulating anti-F8 antibodies unlike animals treated with the single oversized AAV-F8 vector under clinica","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2026-05-09T23:45:58.673Z","creation":"2025-04-04T22:15:20.275Z"},"accession":"S-EPMC9174883","cross_references":{"pubmed":["35491676"],"doi":["10.15252/emmm.202115199"]}}