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Aberrant methylmalonylation underlies methylmalonic acidemia and is attenuated by an engineered sirtuin

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Head, PamelaSara E., Myung, Sangho, Chen, Yong, Schneller, Jessica L., Wang, Cindy, Duncan, Nicholas, Hoffman, Pauline, Chang, David +4 more·2022·Science Translational Medicine
DOI 10.1126/scitranslmed.abn4772PMC PMC10468269
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Abstract

Organic acidemias such as methylmalonic acidemia (MMA) are a group of inborn errors of metabolism that typically arise from defects in the catabolism of amino and fatty acids. Accretion of acyl-CoA species is postulated to underlie disease pathophysiology, but the mechanism(s) remain unknown. Here, we surveyed hepatic explants from patients with MMA and unaffected donors, in parallel with samples from various mouse models of methylmalonyl-CoA mutase deficiency. We found a widespread posttranslational modification, methylmalonylation, that inhibited enzymes in the urea cycle and glycine cleavage pathway in MMA. Biochemical studies and mouse genetics established that sirtuin 5 (SIRT5) controlled the metabolism of MMA-related posttranslational modifications. SIRT5 was engineered to resist acylation-driven inhibition via lysine to arginine mutagenesis. The modified SIRT5 was used to create an adeno-associated viral 8 (AAV8) vector and systemically delivered to mutant and control mice. Gene therapy ameliorated hyperammonemia and reduced global methylmalonylation in the MMA mice.

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  • The succinyllysine antibody used in this study exhibits little to no cross-reactivity to other acyl-species.

    “the succinyllysine antibody used within this study has been shown to exhibit little to no cross-reactivity to these other acyl-species41”

    From Loss of succinyl-CoA synthetase in mouse forebrain results in hypersuccinylation with perturbed neuronal transcription and metabolism (2023) · cites this paper as [41]

    The Discussion describes weak or absent cross-reactivity of a methylmalonyllysine antibody with other acylated lysines. The Results describe an anti-malonyllysine antibody that does not cross-react with succinyllysine. Neither passage establishes the cross-reactivity of a succinyllysine antibody; searches for that antibody and its specificity found no such statement in our copy. (LLM, conf=0.73)

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  1. [1]Fenton WA, Gravel RA, and Rosenblatt DS, in The Metabolic and Molecular Bases of Inherited Disease, Scriver ALBCR, Sly WS, and Valle D, eds., Ed. (McGraw-Hill, New York, 2001), pp. 2165– 2193.
  2. [3]Fraser JL, Venditti CP, Methylmalonic and propionic acidemias: clinical management update. Curr Opin Pediatr 28, 682– 693 (2016). 27653704 PMC5393914
  3. [4]Jafari P, Braissant O, Zavadakova P, Henry H, Bonafe L, Ballhausen D, Brain damage in methylmalonic aciduria: 2-methylcitrate induces cerebral ammonium accumulation and apoptosis in 3D organotypic brain cell cultures. Orphanet J Rare Dis 8, 4 (2013). 23298464 PMC3567978
  4. [5]Manoli I, Venditti CP, Disorders of branched chain amino acid metabolism. Transl Sci Rare Dis 1, 91– 110 (2016). 29152456 PMC5685199
  5. [6]Molema F, Martinelli D, Horster F, Kolker S, Tangeraas T, de Koning B, Dionisi-Vici C, Williams M, additional ERN individual contributors of Metab, Liver and/or kidney transplantation in amino and organic acid-related inborn errors of metabolism: An overview on European data. J Inherit Metab Dis 44, 593– 605 (2021). 32996606 PMC8247334
  6. [7]Baumgartner MR, Horster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, Huemer M, Hochuli M, Assoun M, Ballhausen D, Burlina A, Fowler B, Grunert SC, Grunewald S, Honzik T, Merinero B, Perez-Cerda C, Scholl-Burgi S, Skovby F, Wijburg F, MacDonald A, Martinelli D, Sass JO, Valayannopoulos V, Chakrapani A, Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis 9, 130 (2014). 25205257 PMC4180313
  7. [8]Cosson MA, Benoist JF, Touati G, Dechaux M, Royer N, Grandin L, Jais JP, Boddaert N, Barbier V, Desguerre I, Campeau PM, Rabier D, Valayannopoulos V, Niaudet P, de Lonlay P, Long-term outcome in methylmalonic aciduria: a series of 30 French patients. Mol Genet Metab 97, 172– 178 (2009). 19375370
  8. [9]Nagarajan S, Enns GM, Millan MT, Winter S, Sarwal MM, Management of methylmalonic acidaemia by combined liver-kidney transplantation. J Inherit Metab Dis 28, 517– 524 (2005). 15902554
  9. [10]Mc Guire PJ, Lim-Melia E, Diaz GA, Raymond K, Larkin A, Wasserstein MP, Sansaricq C, Combined liver-kidney transplant for the management of methylmalonic aciduria: a case report and review of the literature. Mol Genet Metab 93, 22– 29 (2008). 17964841 PMC2786260
  10. [11]Niemi AK, Kim IK, Krueger CE, Cowan TM, Baugh N, Farrell R, Bonham CA, Concepcion W, Esquivel CO, Enns GM, Treatment of methylmalonic acidemia by liver or combined liver-kidney transplantation. J Pediatr 166, 1455– 1461 e1451 (2015). 25771389
  11. [12]van ‘t Hoff WG, Dixon M, Taylor J, Mistry P, Rolles K, Rees L, Leonard JV, Combined liver-kidney transplantation in methylmalonic acidemia. J Pediatr 132, 1043– 1044 (1998). 9627602
  12. [13]Sakamoto R, Nakamura K, Kido J, Matsumoto S, Mitsubuchi H, Inomata Y, Endo F, Improvement in the prognosis and development of patients with methylmalonic acidemia after living donor liver transplant. Pediatr Transplant 20, 1081– 1086 (2016). 27670840
  13. [14]Collado MS, Armstrong AJ, Olson M, Hoang SA, Day N, Summar M, Chapman KA, Reardon J, Figler RA, Wamhoff BR, Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes. Mol Genet Metab 130, 183– 196 (2020). 32451238 PMC7337260
  14. [15]Bowman CE, Wolfgang MJ, Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism. Adv Biol Regul 71, 34– 40 (2019). 30201289 PMC6347522
  15. [16]Bowman CE, Rodriguez S, Alpergin ESS, Acoba MG, Zhao L, Hartung T, Claypool SM, Watkins PA, Wolfgang MJ, The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency. Cell Chem Biol 24, 673−+ (2017). 28479296 PMC5482780
  16. [17]Sloan JL, Johnston JJ, Manoli I, Chandler RJ, Krause C, Carrillo-Carrasco N, Chandrasekaran SD, Sysol JR, O’Brien K, Hauser NS, Sapp JC, Dorward HM, Huizing M, Group NIHISC, Barshop BA, Berry SA, James PM, Champaigne NL, de Lonlay P, Valayannopoulos V, Geschwind MD, Gavrilov DK, Nyhan WL, Biesecker LG, Venditti CP, Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Nat Genet 43, 883– 886 (2011). 21841779 PMC3163731
  17. [20]Yang XJ, Seto E, Lysine acetylation: codified crosstalk with other posttranslational modifications. Mol Cell 31, 449– 461 (2008). 18722172 PMC2551738
  18. [21]Glozak MA, Sengupta N, Zhang X, Seto E, Acetylation and deacetylation of non-histone proteins. Gene 363, 15– 23 (2005). 16289629
  19. [22]Ngounou Wetie AG, Woods AG, Darie CC, Mass spectrometric analysis of post-translational modifications (PTMs) and protein-protein interactions (PPIs). Adv Exp Med Biol 806, 205– 235 (2014). 24952184
  20. [23]Wagner GR, Payne RM, Widespread and enzyme-independent Nepsilon-acetylation and Nepsilon-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem 288, 29036– 29045 (2013). 23946487 PMC3790002
  21. [24]Cheng Z, Tang Y, Chen Y, Kim S, Liu H, Li SS, Gu W, Zhao Y, Molecular characterization of propionyllysines in non-histone proteins. Mol Cell Proteomics 8, 45– 52 (2009). 18753126 PMC2621001
  22. [25]Chen Y, Sprung R, Tang Y, Ball H, Sangras B, Kim SC, Falck JR, Peng J, Gu W, Zhao Y, Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics 6, 812– 819 (2007). 17267393 PMC2911958
  23. [26]Sterner DE, Berger SL, Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 64, 435– 459 (2000). 10839822 PMC98999
  24. [27]Hirschey MD, Zhao Y, Metabolic Regulation by Lysine Malonylation, Succinylation, and Glutarylation. Mol Cell Proteomics 14, 2308– 2315 (2015). 25717114 PMC4563717
  25. [28]Kulkarni RA, Worth AJ, Zengeya TT, Shrimp JH, Garlick JM, Roberts AM, Montgomery DC, Sourbier C, Gibbs BK, Mesaros C, Tsai YC, Das S, Chan KC, Zhou M, Andresson T, Weissman AM, Linehan WM, Blair IA, Snyder NW, Meier JL, Discovering Targets of Non-enzymatic Acylation by Thioester Reactivity Profiling. Cell Chem Biol 24, 231– 242 (2017). 28163016 PMC5864104
  26. [29]Pougovkina O, te Brinke H, Wanders RJA, Houten SM, de Boer VCJ, Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism. Journal of Inherited Metabolic Disease 37, 709– 714 (2014). 24531926
  27. [30]Zhao SM, Xu W, Jiang WQ, Yu W, Lin Y, Zhang TF, Yao J, Zhou L, Zeng YX, Li H, Li YX, Shi J, An WL, Hancock SM, He FC, Qin LX, Chin J, Yang PY, Chen X, Lei QY, Xiong Y, Guan KL, Regulation of Cellular Metabolism by Protein Lysine Acetylation. Science 327, 1000– 1004 (2010). 20167786 PMC3232675
  28. [32]Manoli I, Sysol JR, Epping MW, Li L, Wang C, Sloan JL, Pass A, Gagne J, Ktena YP, Li L, Trivedi NS, Ouattara B, Zerfas PM, Hoffmann V, Abu-Asab M, Tsokos MG, Kleiner DE, Garone C, Cusmano-Ozog K, Enns GM, Vernon HJ, Andersson HC, Grunewald S, Elkahloun AG, Girard CL, Schnermann J, DiMauro S, Andres-Mateos E, Vandenberghe LH, Chandler RJ, Venditti CP, FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia. JCI Insight 3, (2018). PMC6328030 30518688
  29. [33]Crane AM, Martin LS, Valle D, Ledley FD, Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase. Hum Genet 89, 259– 264 (1992). 1351030
  30. [34]Froese DS, Fowler B, Baumgartner MR, Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis 42, 673– 685 (2019). 30693532
  31. [38]Rardin MJ, He WJ, Nishida Y, Newman JC, Carrico C, Danielson SR, Guo A, Gut P, Sahu AK, Li B, Uppala R, Fitch M, Riiff T, Zhu L, Zhou J, Mulhern D, Stevens RD, Ilkayeva OR, Newgard CB, Jacobson MP, Hellerstein M, Goetzman ES, Gibson BW, Verdin E, SIRT5 Regulates the Mitochondrial Lysine Succinylome and Metabolic Networks. Cell Metabolism 18, 920– 933 (2013). 24315375 PMC4105152
  32. [40]Hada K, Hirota K, Inanobe A, Kako K, Miyata M, Araoi S, Matsumoto M, Ohta R, Arisawa M, Daitoku H, Hanada T, Fukamizu A, Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans. J Biol Chem 294, 3091– 3099 (2019). 30606736 PMC6398127
  33. [42]Wagner GR, Hirschey MD, Nonenzymatic protein acylation as a carbon stress regulated by sirtuin deacylases. Mol Cell 54, 5– 16 (2014). 24725594 PMC4040445
  34. [43]Huang da W, Sherman BT, Lempicki RA, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4, 44– 57 (2009). 19131956
  35. [44]Huang da W, Sherman BT, Lempicki RA, Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37, 1– 13 (2009). 19033363 PMC2615629
  36. [45]Zhou G, Soufan O, Ewald J, Hancock REW, Basu N, Xia J, NetworkAnalyst 3.0: a visual analytics platform for comprehensive gene expression profiling and meta-analysis. Nucleic Acids Res 47, W234– W241 (2019). 30931480 PMC6602507
  37. [46]Xia J, Gill EE, Hancock RE, NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data. Nat Protoc 10, 823– 844 (2015). 25950236
  38. [47]Xia J, Benner MJ, Hancock RE, NetworkAnalyst--integrative approaches for protein-protein interaction network analysis and visual exploration. Nucleic Acids Res 42, W167– 174 (2014). 24861621 PMC4086107
  39. [48]Xia J, Lyle NH, Mayer ML, Pena OM, Hancock RE, INVEX--a web-based tool for integrative visualization of expression data. Bioinformatics 29, 3232– 3234 (2013). 24078684 PMC3842763
  40. [49]Xia J, Fjell CD, Mayer ML, Pena OM, Wishart DS, Hancock RE, INMEX--a web-based tool for integrative meta-analysis of expression data. Nucleic Acids Res 41, W63– 70 (2013). 23766290 PMC3692077
  41. [51]Pierson DL, A rapid colorimetric assay for carbamyl phosphate synthetase I. J Biochem Biophys Methods 3, 31– 37 (1980). 7451805
  42. [52]Amaral AU, Cecatto C, Castilho RF, Wajner M, 2-Methylcitric acid impairs glutamate metabolism and induces permeability transition in brain mitochondria. J Neurochem 137, 62– 75 (2016). 26800654
  43. [53]Aleshin VA, Mkrtchyan GV, Kaehne T, Graf AV, Maslova MV, Bunik VI, Diurnal regulation of the function of the rat brain glutamate dehydrogenase by acetylation and its dependence on thiamine administration. J Neurochem 153, 80– 102 (2020). 31886885
  44. [54]Caterino M, Chandler RJ, Sloan JL, Dorko K, Cusmano-Ozog K, Ingenito L, Strom SC, Imperlini E, Scolamiero E, Venditti CP, Ruoppolo M, The proteome of methylmalonic acidemia (MMA): the elucidation of altered pathways in patient livers. Mol Biosyst 12, 566– 574 (2016). 26672496 PMC4858437
  45. [55]King GA, Hashemi Shabestari M, Taris KH, Pandey AK, Venkatesh S, Thilagavathi J, Singh K, Krishna Koppisetti R, Temiakov D, Roos WH, Suzuki CK, Wuite GJL, Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms. Nucleic Acids Res 46, 3633– 3642 (2018). 29897602 PMC5909435
  46. [56]Minczuk M, He J, Duch AM, Ettema TJ, Chlebowski A, Dzionek K, Nijtmans LG, Huynen MA, Holt IJ, TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res 39, 4284– 4299 (2011). 21278163 PMC3105396
  47. [57]Chandler RJ, Zerfas PM, Shanske S, Sloan J, Hoffmann V, DiMauro S, Venditti CP, Mitochondrial dysfunction in mut methylmalonic acidemia. FASEB J 23, 1252– 1261 (2009). 19088183 PMC2660647
  48. [58]Manoli I, Sysol JR, Li L, Houillier P, Garone C, Wang C, Zerfas PM, Cusmano-Ozog K, Young S, Trivedi NS, Cheng J, Sloan JL, Chandler RJ, Abu-Asab M, Tsokos M, Elkahloun AG, Rosen S, Enns GM, Berry GT, Hoffmann V, DiMauro S, Schnermann J, Venditti CP, Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia. Proc Natl Acad Sci U S A 110, 13552– 13557 (2013). 23898205 PMC3746875
  49. [59]Luciani A, Denley MCS, Govers LP, Sorrentino V, Froese DS, Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia. Cell Mol Life Sci 78, 6851– 6867 (2021). 34524466 PMC8558192
  50. [60]Childs B, Nyhan WL, Borden M, Bard L, Cooke RE, Idiopathic hyperglycinemia and hyperglycinuria: a new disorder of amino acid metabolism. I. Pediatrics 27, 522– 538 (1961). 13693094
  51. [61]Childs B, Nyhan WL, Further Observations of a Patient with Hyperglycinemia. Pediatrics 33, 403– 412 (1964). 14129085
  52. [62]Hommes FA, Kuipers JR, Elema JD, Jansen JF, Jonxis JH, Propionicacidemia, a new inborn error of metabolism. Pediatr Res 2, 519– 524 (1968). 5727920
  53. [63]Hsia YE, Scully KJ, Rosenberg LE, Defective propionate carboxylation in ketotic hyperglycinaemia. Lancet 1, 757– 758 (1969). 4180220
  54. [66]Shimazu T, Hirschey MD, Hua L, Dittenhafer-Reed KE, Schwer B, Lombard DB, Li Y, Bunkenborg J, Alt FW, Denu JM, Jacobson MP, Verdin E, SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production. Cell Metab 12, 654– 661 (2010). 21109197 PMC3310379
  55. [67]Choi JE, Mostoslavsky R, Sirtuins, metabolism, and DNA repair. Curr Opin Genet Dev 26, 24– 32 (2014). 25005742 PMC4254145
  56. [68]Schneller JL, Lee CM, Chandler RJ, Venturoni LE, Li A, Myung S, Cradick TJ, Hurley AE, Lagor WR, Bao G, Venditti CP, In Vivo Genome Editing at the Albumin Locus to TreatMethylmalonic Acidemia (MMA). Molecular Therapy-Methods and Clinical Development, (2021). PMC8634044 34901307
  57. [69]Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis M, Guarente LP, Farese RV Jr., Weissman S, Verdin E, Schwer B, Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27, 8807– 8814 (2007). 17923681 PMC2169418
  58. [70]Sanderson S, Green A, Preece MA, Burton H, The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 91, 896– 899 (2006). 16690699 PMC2082934
  59. [71]Gueant JL, Gueant-Rodriguez RM, Kosgei VJ, Coelho D, Causes and consequences of impaired methionine synthase activity in acquired and inherited disorders of vitamin B12 metabolism. Crit Rev Biochem Mol Biol, 1– 23 (2021). 34608838
  60. [72]Wu J, Liu J, Lapenta K, Desrouleaux R, Li MD, Yang X, Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. J Mol Cell Biol, (2022). PMC9254885 35285892
  61. [74]Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S, Madden TL, NCBI BLAST: a better web interface. Nucleic Acids Res 36, W5– 9 (2008). 18440982 PMC2447716
  62. [75]Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E, PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res 43, D512– 520 (2015). 25514926 PMC4383998
  63. [76]Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR, A method and server for predicting damaging missense mutations. Nat Methods 7, 248– 249 (2010). 20354512 PMC2855889
  64. [78]Crooks GE, Hon G, Chandonia JM, Brenner SE, WebLogo: a sequence logo generator. Genome Res 14, 1188– 1190 (2004). 15173120 PMC419797
  65. [79]Schneider TD, Stephens RM, Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18, 6097– 6100 (1990). 2172928 PMC332411
  66. [80]Chandler RJ, Venditti CP, Long-term rescue of a lethal murine model of methylmalonic acidemia using adeno-associated viral gene therapy. Mol Ther 18, 11– 16 (2010). 19861951 PMC2839224
  67. [81]Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM, Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A 99, 11854– 11859 (2002). 12192090 PMC129358

Cited by

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Authors
Head, P. E., Myung, S., Chen, Y., Schneller, J. L., Wang, C., Duncan, N., Hoffman, P., Chang, D., Gebremariam, A., Gucek, M., Manoli, I., & Venditti, C. P.
Affiliations
  • National Institutes of Health (US)
  • National Heart Lung and Blood Institute, NIH, 31 Center Drive, Building 31, Bethesda, MD 20892, USA.
Corresponding author
Venditti, Charles P.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-05-25
Volume
14
Issue
646
Pages
eabn4772-eabn4772
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.abn4772
PMC
PMC10468269
OpenAlex
W4281487571
Cited by
52
References
9
Citations by year
2026: 8 · 2025: 14 · 2024: 12 · 2023: 13 · 2022: 5
FWCI
7.65
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute
  • National Human Genome Research Institute (ZIAHG200318)
  • National Institute of General Medical Sciences (FI2GM137781)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
methylmalonic acidemia, SIRT5, post-translational modification, methylmalonyl-CoA mutase deficiency, organic aciduria, inborn errors of metabolism, urea cycle, gene therapy, adeno-associated virus vectors, hyperammonemia
MeSH terms
Amino Acid Metabolism, Inborn Errors, Animals, Humans, Methylmalonyl-CoA Mutase, Genetic Therapy, Sirtuins, Mice

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