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Ltd."},{"name":"Nonhuman Primates-Associates, Cooperative Research Program of Primate Research Institute, Kyoto University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder (LSD) caused by recessive mutations in the \u03b1-L-iduronidase (\n                      <jats:italic>IDUA<\/jats:italic>\n                      ) gene. Enzyme replacement therapy (ERT) utilizing terminal mannose-6-phosphate (M6P)-carrying\n                      <jats:italic>N<\/jats:italic>\n                      -glycans attached to therapeutic enzymes produced by mammalian cell lines has been clinically applied to several LSDs. Recent studies suggested an unidentified delivery pathway mediated by sialic acid-containing\n                      <jats:italic>N<\/jats:italic>\n                      -glycans. However, more economical platform development is required to produce large quantities of recombinant enzymes. Transgenic silkworms have been established as low-cost systems for expressing recombinant glycoproteins. Microbial endo-\u03b2-\n                      <jats:italic>N<\/jats:italic>\n                      -acetylglucosaminidases (ENGases) enable the transglycosylation of\n                      <jats:italic>N<\/jats:italic>\n                      -glycans to other types.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We purified recombinant human IDUA from\n                      <jats:italic>IDUA<\/jats:italic>\n                      transgenic silkworm cocoons and performed ENGase-mediated transglycosylation. Furthermore, we performed intravenous enzyme replacement therapy in a Japanese macaque MPS I non-human primate model carrying a homozygous\n                      <jats:italic>IDUA<\/jats:italic>\n                      missense mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Here we show the establishment of\n                      <jats:italic>IDUA<\/jats:italic>\n                      transgenic silkworms and purification of recombinant human IDUA from cocoons. As M6P- and sialic acid-containing\n                      <jats:italic>N<\/jats:italic>\n                      -glycans are not attached to purified hIDUA, we perform ENGase-mediated transglycosylation to obtain hIDUAs with M6P- and sialic acid-containing\n                      <jats:italic>N<\/jats:italic>\n                      -glycans (neoglyco-hIDUAs). Furthermore, we perform intravenous neoglyco-hIDUA replacement therapy in MPS I non-human primate model and succeed in improving the clinical signs and reducing the urinary glycosaminoglycan (GAG) levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These glycotechnologies using transgenic silkworms and ENGases are expected to serve as platforms for developing therapeutic glycoproteins.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-025-00841-7","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T14:06:27Z","timestamp":1744985187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["N-glycan-modified \u03b1-L-iduronidase produced by transgenic silkworms ameliorates clinical signs in a Japanese macaque with 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