{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Diep T"],"funding":["National Institute of Neurological Disorders and Stroke","Swiss National Science Foundation","NINDS NIH HHS"],"pagination":["102470"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11905892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["36(1)"],"pubmed_abstract":["Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat <i>CPS1</i> deficiency. In order to constrain genome size, we utilized small liver-specific promoter/enhancers and a minimal polyadenylation signal. Long-term survival (9 months, end of study) with ammonia control was achieved in AAV8.CPS1-administered Cps1<sup>fl"],"journal":["Molecular therapy. Nucleic acids"],"pubmed_title":["Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control."],"pmcid":["PMC11905892"],"funding_grant_id":["320030","R61 NS121348","207965"],"pubmed_authors":["Barshop BA","Diep T","Makris G","Zhou W","Reyes RE","Nitzahn M","Day IL","Lueptow L","Li Y","Zhuravka I","Gangoiti J","Lipshutz GS","Bakshi S","Padaon H","Haberle J"],"additional_accession":[]},"is_claimable":false,"name":"Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.","description":"Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat <i>CPS1</i> deficiency. In order to constrain genome size, we utilized small liver-specific promoter/enhancers and a minimal polyadenylation signal. Long-term survival (9 months, end of study) with ammonia control was achieved in AAV8.CPS1-administered Cps1<sup>fl","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-06-01T22:56:55.722Z","creation":"2025-04-06T10:51:12.238Z"},"accession":"S-EPMC11905892","cross_references":{"pubmed":["40083646"],"doi":["10.1016/j.omtn.2025.102470"]}}