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Ancestral lysosomal...
Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
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- Hendrikse, Natalie (author)
- KTH,Ytbehandlingsteknik,Science for Life Laboratory, SciLifeLab,Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Sandegren, Anna (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Andersson, Tommy (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Blomqvist, Jenny (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Makower, Asa (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Possner, Dominik (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Su, Chao (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Thalén, Niklas (author)
- KTH,Proteinteknologi
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- Tjernberg, Agneta (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Westermark, Ulrica (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Rockberg, Johan (author)
- KTH,Proteinteknologi
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- Gelius, Stefan Svensson (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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- Syrén, Per-Olof (author)
- KTH,Science for Life Laboratory, SciLifeLab,Ytbehandlingsteknik,Proteinvetenskap
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- Nordling, Erik (author)
- Swedish Orphan Biovitrum AB, S-11276 Stockholm, Sweden.
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
- Related links:
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https://doi.org/10.1...
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http://www.cell.com/...
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Abstract
Subject headings
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- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
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- ref (subject category)
- art (subject category)
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ISCIENCE
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- By the author/editor
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Hendrikse, Natal ...
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Sandegren, Anna
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Andersson, Tommy
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Blomqvist, Jenny
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Makower, Asa
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Possner, Dominik
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Su, Chao
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Thalén, Niklas
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Tjernberg, Agnet ...
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Westermark, Ulri ...
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Rockberg, Johan
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Gelius, Stefan S ...
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Syrén, Per-Olof
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Nordling, Erik
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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ISCIENCE
- By the university
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Royal Institute of Technology