{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:15:15Z","timestamp":1787944515968,"version":"build-2784847793"},"reference-count":85,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"787","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/www.science.org\/content\/page\/science-licenses-journal-article-reuse"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,2,26]]},"abstract":"<jats:p>\n            Classic maple syrup urine disease (MSUD) results from biallelic mutations in genes that encode the\n            <jats:italic>branched-chain \u03b1-ketoacid dehydrogenase E1<\/jats:italic>\n            \u03b1 (\n            <jats:italic>BCKDHA<\/jats:italic>\n            ),\n            <jats:italic>E1<\/jats:italic>\n            \u03b2 (\n            <jats:italic>BCKDHB<\/jats:italic>\n            ), or\n            <jats:italic>dihydrolipoamide branched-chain transacylase<\/jats:italic>\n            (\n            <jats:italic>DBT<\/jats:italic>\n            ) subunits, which interact to form the mitochondrial BCKDH complex that decarboxylates ketoacid derivatives of leucine, isoleucine, and valine. MSUD is an inborn error of metabolism characterized by recurrent life-threatening neurologic crises and progressive brain injury that can only be managed with an exacting prescription diet or allogeneic liver transplant. To develop a gene replacement therapy for MSUD, we designed a dual-function recombinant adeno-associated virus serotype 9 (rAAV9) vector to deliver codon-optimized\n            <jats:italic>BCKDHA<\/jats:italic>\n            and\n            <jats:italic>BCKDHB<\/jats:italic>\n            (rAAV9.h\n            <jats:italic>A<\/jats:italic>\n            -BiP-h\n            <jats:italic>B<\/jats:italic>\n            ) to the liver, muscle, heart, and brain. rAAV9.h\n            <jats:italic>A<\/jats:italic>\n            -BiP-h\n            <jats:italic>B<\/jats:italic>\n            restored coexpression of BCKDHA and BCKDHB as well as BCKDH holoenzyme activity in\n            <jats:italic>\n              BCKDHA\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            HEK293T cells and did not perturb physiologic branched-chain amino acid homeostasis in wild-type mice at a systemic dose of 2.7 \u00d7 10\n            <jats:sup>14<\/jats:sup>\n            vector genomes per kilogram. In two models of severe MSUD (\n            <jats:italic>\n              Bckdha\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            and\n            <jats:italic>\n              Bckdhb\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <\/jats:italic>\n            mice) and a newborn calf homozygous for\n            <jats:italic>BCKDHA<\/jats:italic>\n            c.248C&gt;T, one postnatal injection prevented perinatal death, normalized growth, restored coordinated expression of BCKDHA and BCKDHB in the skeletal muscle, liver, heart, and brain, and stabilized MSUD biomarkers in the face of high protein ingestion. In summary, we developed a one-time\n            <jats:italic>BCKDHA-BCKDHB<\/jats:italic>\n            systemic dual-gene replacement strategy that holds promise as a therapeutic alternative to prescription diet and liver transplant for treatment of MSUD types 1A and 1B, the two most common forms of MSUD in humans.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.ads0539","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T18:59:56Z","timestamp":1740596396000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":13,"title":["<i>BCKDHA-BCKDHB<\/i>\n            digenic gene therapy restores metabolic homeostasis in two mouse models and a calf with classic maple syrup urine disease"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-967X","authenticated-orcid":true,"given":"Jiaming","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0358-2723","authenticated-orcid":true,"given":"Laura E.","family":"Poskitt","sequence":"additional","affiliation":[{"name":"Clinic for Special Children, Gordonville, PA 17529, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-0801","authenticated-orcid":true,"given":"Jillian","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik G.","family":"Puffenberger","sequence":"additional","affiliation":[{"name":"Clinic for Special Children, Gordonville, PA 17529, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Max","family":"Wynn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, TX 75390, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri","family":"Shishodia","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, TX 75390, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical School, Dallas, TX 75390, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Beever","sequence":"additional","affiliation":[{"name":"Department of Animal Science and Large Animal Clinical Sciences, University of Tennessee Institute of Agriculture, Knoxville, TN 37996, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Hardin","sequence":"additional","affiliation":[{"name":"Longview Farms, New Virginia, IA 50210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9178-815X","authenticated-orcid":true,"given":"Karlla W.","family":"Brigatti","sequence":"additional","affiliation":[{"name":"Clinic for Special Children, Gordonville, PA 17529, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2594-6575","authenticated-orcid":true,"given":"William C.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0559-2801","authenticated-orcid":true,"given":"Rachael","family":"Gately","sequence":"additional","affiliation":[{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlin","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Clinic for Special Children, Gordonville, PA 17529, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-5060","authenticated-orcid":true,"given":"Hector R","family":"Benatti","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-4733","authenticated-orcid":true,"given":"Toloo","family":"Taghian","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0519-427X","authenticated-orcid":true,"given":"Rachel","family":"Prestigiacomo","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2616-2853","authenticated-orcid":true,"given":"Gong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-3529","authenticated-orcid":true,"given":"Xuntao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9557-6017","authenticated-orcid":true,"given":"Nan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"He","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9565-1567","authenticated-orcid":true,"given":"Jun","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-8391","authenticated-orcid":true,"given":"Alisha","family":"Gruntman","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."},{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-3159","authenticated-orcid":true,"given":"Heather","family":"Gray-Edwards","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."},{"name":"Tufts University Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-9012","authenticated-orcid":true,"given":"Guangping","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."},{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-8657","authenticated-orcid":true,"given":"Kevin A.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."},{"name":"Clinic for Special Children, Gordonville, PA 17529, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-2360","authenticated-orcid":true,"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."},{"name":"RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.01.006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2005.01209.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/45.10.1734"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.07.009"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jped.2014.08.010"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.04.007"},{"key":"e_1_3_2_8_2","first-page":"8","article-title":"Maple syrup urine disease-treatment and outcome in patients of Turkish descent in Germany","volume":"47","author":"Simon E.","year":"2005","unstructured":"E. Simon, U. Wendel, P. Schadewaldt, Maple syrup urine disease-treatment and outcome in patients of Turkish descent in Germany. Turk. J. Pediatr. 47, 8\u201313 (2005).","journal-title":"Turk. J. Pediatr."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-020-01376-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-008-0859-0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/323677"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.20003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2012.76"},{"key":"e_1_3_2_14_2","unstructured":"K. A. Strauss E. G. Puffenberger V. J. Carson \u201cMaple syrup urine disease\u201d in GeneReviews [Internet] M. P. Adam D. B. Everman G. M. Mirzaa R. A. Pagon S. E. Wallace L. J. H. Bean K. W. Gripp A. Amemiya Eds. (University of Washington 1993)."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-017-0083-x"},{"key":"e_1_3_2_16_2","unstructured":"K. A. Strauss E. G. Puffenberger D. H. Morton \u201cMaple syrup urine disease\u201d in GeneReviews [Internet] M. P. Adam D. B. Everman G. M. Mirzaa R. A. Pagon S. E. Wallace L. J. H. Bean K. W. Gripp A. Amemiya Eds. (University of Washington 2009)."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.12.007"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/135.6.1531S"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","unstructured":"Q. R. Smith J. S. Stoll in Introduction to the Blood-Brain Barrier W. M. Pardridge Ed. (Cambridge Univ. Press 1998) vol. 1 pp. 188\u2013197.","DOI":"10.1017\/CBO9780511570216.020"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.109.6.999"},{"key":"e_1_3_2_21_2","first-page":"110","article-title":"Real-world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid-free formulas in France and Germany: A retrospective observational study","volume":"59","author":"de Lonlay P.","year":"2021","unstructured":"P. de Lonlay, R. Posset, U. Mutze, K. Mention, D. Lamireau, M. Schiff, A. Servais, J. B. Arnoux, A. Brassier, M. Dao, C. Douillard, C. Ottolenghi, C. Pontoizeau, F. Miotto, J. Le Mouhaer, Real-world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid-free formulas in France and Germany: A retrospective observational study. JIMD Rep. 59, 110\u2013119 (2021).","journal-title":"JIMD Rep."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67217"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.06.033"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2012.04.031"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/68.1.72"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.63041508.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00042"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01483-7"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-0813.1989.tb03014.x"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1053\/rvsc.1998.0296"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005322010854"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.119.3.62"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb09409.x"},{"key":"e_1_3_2_34_2","first-page":"204037","article-title":"Maple syrup urine disease in a central Indiana Hereford herd","volume":"2015","author":"Robarge M. E.","year":"2015","unstructured":"M. E. Robarge, J. E. Beever, S. D. Lenz, C. J. Lynch, W. L. Wigle, Maple syrup urine disease in a central Indiana Hereford herd. Case Rep. Vet. Med. 2015, 204037 (2015).","journal-title":"Case Rep. Vet. Med."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1966.tb05882.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2010.01411.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"K. A. Strauss in Pediatric Critical Care: Text and Study Guide S. E. Lucking F. A. Maffei R. F. Tamburro A. Zaritsky Eds. (Springer Cham 2021) pp. 1351\u20131396.","DOI":"10.1007\/978-3-030-53363-2_44"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115363"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.76"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.72"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2950635"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0887-8994(92)90038-Z"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2011.183"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1224631"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad010"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.1.207S"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0065-2571(86)90016-6"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvfa.2014.11.006"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.021"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.09.017"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30880-w"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12604"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.08.003"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42045-5"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.66010378.x"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/131.3.846S"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp024"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01866-4"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0475-4"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1967.tb09500.x"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410330412"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-003-1058-7"},{"key":"e_1_3_2_64_2","first-page":"162","article-title":"Water apparent diffusion coefficient and T2 changes in the acute stage of maple syrup urine disease: Evidence of intramyelinic and vasogenic-interstitial edema","volume":"13","author":"Righini A.","year":"2003","unstructured":"A. Righini, L. A. Ramenghi, R. Parini, F. Triulzi, F. Mosca, Water apparent diffusion coefficient and T2 changes in the acute stage of maple syrup urine disease: Evidence of intramyelinic and vasogenic-interstitial edema. J. Neuroimaging 13, 162\u2013165 (2003).","journal-title":"J. Neuroimaging"},{"key":"e_1_3_2_65_2","first-page":"648","article-title":"Cerebral edema in maple syrup urine disease","volume":"136","author":"Lungarotti M. S.","year":"1982","unstructured":"M. S. Lungarotti, A. Calabro, E. Signorini, L. R. Garibaldi, Cerebral edema in maple syrup urine disease. Am. J. Dis. Child. 136, 648 (1982).","journal-title":"Am. J. Dis. Child."},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13539-011-0042-6"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665199001305"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1177\/014860719101500386S"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1051\/rnd:19950604"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2006-373"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/7340495"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.12.031"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79213"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.17"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.160"},{"key":"e_1_3_2_76_2","first-page":"1081","article-title":"Prevalent and disseminated recombinant and wild-type adeno-associated virus integration in macaques and humans","volume":"34","author":"Martins K. M.","year":"2023","unstructured":"K. M. Martins, C. Breton, Q. Zheng, Z. Zhang, C. Latshaw, J. A. Greig, J. M. Wilson, Prevalent and disseminated recombinant and wild-type adeno-associated virus integration in macaques and humans. Hum. Gene Ther. 34, 1081\u20131094 (2023).","journal-title":"Hum. Gene Ther."},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01974-7"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.06.004"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00056"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(00)24231-6"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.569251"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(60)90197-1"},{"key":"e_1_3_2_83_2","first-page":"1445","article-title":"Maple syrup urine disease (branched chain ketoaciduria)","volume":"136","author":"Harper P. A.","year":"1990","unstructured":"P. A. Harper, P. J. Healy, J. A. Dennis, Maple syrup urine disease (branched chain ketoaciduria). Am. J. Pathol. 136, 1445\u20131447 (1990).","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_84_2","unstructured":"K. A. Strauss in Pediatric Critical Care S. E. Lucking Ed. (Springer Nature 2021)."},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20143830"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005540016376"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.ads0539","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.ads0539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T18:01:14Z","timestamp":1741888874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.ads0539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,26]]},"references-count":85,"journal-issue":{"issue":"787","published-print":{"date-parts":[[2025,2,26]]}},"alternative-id":["10.1126\/scitranslmed.ads0539"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.ads0539","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,26]]},"assertion":[{"value":"2024-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eads0539"}}