A recombinant polypeptide extends the in vivo half-life of peptides and proteins in a tunable manner View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-12

AUTHORS

Volker Schellenberger, Chia-Wei Wang, Nathan C Geething, Benjamin J Spink, Andrew Campbell, Wayne To, Michael D Scholle, Yong Yin, Yi Yao, Oren Bogin, Jeffrey L Cleland, Joshua Silverman, Willem P C Stemmer

ABSTRACT

Increasing the in vivo residence times of protein therapeutics could decrease their dosing frequencies. We show that genetic fusion of an unstructured recombinant polypeptide of 864 amino acids, called XTEN, to a peptide or protein provides an apparently generic approach to extend plasma half-life. Allometric scaling suggests that a fusion of XTEN to the exenatide peptide should increase exenatide half-life in humans from 2.4 h to a projected time of 139 h. We confirmed the biological activity of the exenatide-XTEN fusion in mice. As extended stability might exacerbate undesirable side effects in some cases, we show that truncating the XTEN sequence can regulate plasma half-life. XTEN lacks hydrophobic amino acid residues that often contribute to immunogenicity and complicate manufacture. Based on data on XTEN fusions to exenatide, glucagon, GFP and human growth hormone, we expect that XTEN will enable dosing of otherwise rapidly cleared protein drugs at up to monthly intervals in humans. More... »

PAGES

1186-1190

References to SciGraph publications

Journal

TITLE

Nature Biotechnology

ISSUE

12

VOLUME

27

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nbt.1588

    DOI

    http://dx.doi.org/10.1038/nbt.1588

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022421691

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19915550


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