Enzyme replacement for GM1-gangliosidosis: Uptake, lysosomal activation, and cellular disease correction using a novel β-galactosidase:RTB lectin fusion

Molecular Genetics and Metabolism
Jose CondoriDavid N Radin

Abstract

New enzyme delivery technologies are required for treatment of lysosomal storage disorders with significant pathologies associated with the so-called "hard-to-treat" tissues and organs. Genetic deficiencies in the GLB1 gene encoding acid β-galactosidase lead to GM1-gangliosidosis or Morquio B, lysosomal diseases with predominant disease manifestation associated with the central nervous system or skeletal system, respectively. Current lysosomal ERTs are delivered into cells based on receptor-mediated endocytosis and do not effectively address several hard-to-treat organs including those critical for GM1-gangliosidosis patients. Lectins provide alternative cell-uptake mechanisms based on adsorptive-mediated endocytosis and thus may provide unique biodistribution for lysosomal disease therapeutics. In the current study, genetic fusions of the plant galactose/galactosamine-binding lectin, RTB, and the human acid β-galactosidase enzyme were produced using a plant-based bioproduction platform. β-gal:RTB and RTB:β-gal fusion products retained both lectin activity and β-galactosidase activity. Purified proteins representing both fusion orientations were efficiently taken up into GM1 patient fibroblasts and mediated the reduction of GM1...Continue Reading

References

Jan 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R D BroadwellM Salcman
Aug 15, 1994·Archives of Biochemistry and Biophysics·A V Pshezhetsky, M Potier
May 16, 1997·Carbohydrate Research·A E FrankelM C Willingham
Nov 20, 1998·Journal of Neuroscience Research·W A Banks, A J Kastin
Jun 22, 1999·FEBS Letters·K Sandvig, B van Deurs
Feb 15, 2001·The New England Journal of Medicine·E D KakkisE F Neufeld
Jan 28, 2003·Vaccine·Fabricio Medina-BolivarCarole L Cramer
Mar 4, 2003·The Journal of Biological Chemistry·Juliette Morlon-GuyotBruno Beaumelle
Feb 19, 2004·Advanced Drug Delivery Reviews·Christiane BiesJohn F Woodley
Mar 9, 2004·Current Opinion in Plant Biology·Véronique Gomord, Loïc Faye
Apr 17, 2004·Journal of Neurochemistry·Julie L KasperzykThomas N Seyfried
May 6, 2004·The Journal of Pediatrics·Paul HarmatzJohn J Hopwood
Nov 24, 2004·Lancet Neurology·Roscoe O Brady, Raphael Schiffmann
Apr 9, 2005·Gene Therapy·K Sandvig, B van Deurs
Nov 10, 2005·JAMA : the Journal of the American Medical Association·Jennifer AudiJohn Osterloh
Jul 15, 2006·Current Opinion in Pharmacology·William M Pardridge
Mar 7, 2008·Expert Opinion on Emerging Drugs·Gregory A Grabowski
Apr 5, 2008·Molecular Genetics and Metabolism·Elena Elliot-SmithFrances M Platt
Aug 30, 2008·The AAPS Journal·Françoise HervéJean-Michel Scherrmann
Aug 1, 2009·Journal of Human Genetics·Mizuki MoritaHitoshi Sakuraba
Dec 17, 2009·The Plant Journal : for Cell and Molecular Biology·Emmanuelle GracietFrank Wellmer
Aug 3, 2010·Expert Review of Vaccines·Tatiana V KomarovaYuri L Dorokhov
Feb 19, 2011·The Journal of Biological Chemistry·Shen ShenAravind Asokan
Mar 2, 2011·Human Vaccines·Kevin J WhaleyLarry Zeitlin
Apr 20, 2012·Journal of Virology·Christie L BellJames M Wilson

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Citations

Dec 8, 2016·Molecular Genetics and Metabolism·Gregory A Grabowski, Chester Whitley
Jun 22, 2017·Therapeutic Delivery·Scott N DeanScott A Walper
Sep 10, 2019·JIMD Reports·Luciana GiuglianiRoberto Giugliani
Feb 7, 2020·International Journal of Molecular Sciences·Walter Acosta, Carole L Cramer
Sep 24, 2020·International Journal of Molecular Sciences·Alex E RyckmanJagdeep S Walia
Dec 11, 2019·Scientific Reports·Ruben J BoadoWilliam M Pardridge
Dec 12, 2020·Frontiers in Molecular Biosciences·Mariola J Edelmann, Gustavo H B Maegawa
Apr 17, 2021·The Application of Clinical Genetics·Allisandra K RhaDouglas R Martin
Apr 16, 2021·Molecular Genetics and Metabolism Reports·Michael J PrzybillaChester B Whitley
May 14, 2021·Science Advances·Alexei GorelikMohammad T Mazhab-Jafari
Jun 3, 2021·International Journal of Molecular Sciences·Brianna M QuinvilleJagdeep S Walia
Nov 25, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Arnold E StützTanja M Wrodnigg

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