Future perspectivePreviously we also successfully replaced the terminal sialic acid-containing glycan (SG) with N-glycans attached to cocoon-derived IDUA while retaining the IDUA activity using Endo-CC N180H and egg yolk-derived terminal sialic acid-containing glycopeptide (SGP) as a homogeneous N-glycan donor in a one-pot reaction. We are planning to perform iv ERT for MPS1 Japanese macaque animal using purified SG-type IDUA under the same administration protocol. NeoglycoIDUA carrying sialylglycans will be expected to exhibit novel biodistribution and functions to have further therapeutic effects on MPS1 monkeys.Our approach to producing “Neoglycoenzymes” by transglycosylation technology using ENGases and biofunctional homogeneous N-glycans will be helpful for clinical application to treat neurovisceral symptoms of LSDs and other diseases caused by enzyme dysfunction.Development of neoglycobiologics using transglycosylation technologyKohji ItohReferences1) Wang, J et al. Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment. Nat Biotechnol (26):901-908, 2008.2) Tamura, T et al. Germline transformation of the silkworm Bombyx mori L. using a piggyBac transposon-derived vector. Nat Biotechnol (18):81-84, 2000.3) Kuroguchi, M et al. Glycoengineered monoclonal antibodies with homogeneous glycan (M3, G0, G2, and A2) using a chemoenzymatic approach have different affinities for FcγRIIIa and variable antibody-dependent cellular cytotoxicity activities. PLoS One (10):e0132848, 2015.4) Kiyoshi, M et al. Structural insight and stability of TNFR-Fc fusion protein (Etanercept) produced by using transgenic silkworms. J Biochem (169):25-33, 2021.5) Yamamoto, K. Recent advances in glycotechnology for glycoconjugate synthesis using microbial endoglycosidases. Biotechnol Lett (35):1733-1743, 2013.6) Eshima, Y et al. Transglycosylation activity of glycosynthase mutants of endo-β-N-acetylglucosaminidase from Coprinopsis cinerea. PLoS One (10):e0132859, 2015.7) Itoh, K et al. Recent progress in development of transgenic silkworms overexpressing recombinant human proteins with therapeutic potential in silk glands. Drug Discoveries & Therapeutics (10):34–39, 2016.8) Kakkis, ED et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med (344):182-188, 2001.9) Kiriyama, K & Itoh, K. Glycan recognition and application of P-type lectins. Methods Mol Biol (2132):267–276, 2020.90
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