{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:54:41Z","timestamp":1780980881078,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research","award":["Project FISR2019_04835"],"award-info":[{"award-number":["Project FISR2019_04835"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The gyrate atrophy of the choroid and retina (GACR) is a rare genetic disease for which no definitive cure is available. GACR is due to the deficit of ornithine aminotransferase (hOAT), a pyridoxal 5\u2032-phosphate-dependent enzyme responsible for ornithine catabolism. The hallmark of the disease is plasmatic ornithine accumulation, which damages retinal epithelium leading to progressive vision loss and blindness within the fifth decade. Here, we characterized the biochemical properties of tetrameric and dimeric hOAT and evaluated hOAT loaded in red blood cells (RBCs) as a possible enzyme replacement therapy (ERT) for GACR. Our results show that (i) hOAT has a relatively wide specificity for amino acceptors, with pyruvate being the most suitable candidate for ornithine catabolism within RBCs; (ii) both the tetrameric and dimeric enzyme can be loaded in RBC retaining their activity; and (iii) hOAT displays reduced stability in plasma, but is partly protected from inactivation upon incubation in a mixture mimicking the intracellular erythrocyte environment. Preliminary ex vivo experiments indicate that hOAT-loaded RBCs are able to metabolize extracellular ornithine at a concentration mimicking that found in patients, both in buffer and, although with lower efficiency, in plasma. Overall, our data provide a proof of concept that an RBC-mediated ERT is feasible and can be exploited as a new therapeutic approach in GACR.<\/jats:p>","DOI":"10.3390\/ijms25147931","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T07:57:23Z","timestamp":1721721443000},"page":"7931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biochemical Studies on Human Ornithine Aminotransferase Support a Cell-Based Enzyme Replacement Therapy in the Gyrate Atrophy of the Choroid and Retina"],"prefix":"10.3390","volume":"25","author":[{"given":"Gioena","family":"Pampalone","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Chiasserini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pierig\u00e8","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-0849","authenticated-orcid":false,"given":"Emidio","family":"Camaioni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Orvietani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Bregalda","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5206-6296","authenticated-orcid":false,"given":"Michele","family":"Menotta","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-1600","authenticated-orcid":false,"given":"Ilaria","family":"Bellezza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5221-9288","authenticated-orcid":false,"given":"Barbara","family":"Cellini","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6456-6626","authenticated-orcid":false,"given":"Mauro","family":"Magnani","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ginguay, A., Cynober, L., Curis, E., and Nicolis, I. (2017). Ornithine Aminotransferase, an Important Glutamate-Metabolizing Enzyme at the Crossroads of Multiple Metabolic Pathways. 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