Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09-26

AUTHORS

Philip M Zakas, Harrison C Brown, Kristopher Knight, Shannon L Meeks, H Trent Spencer, Eric A Gaucher, Christopher B Doering

ABSTRACT

Optimization of a protein's pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability, and biosynthesis potential and reduced inhibition by anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence. More... »

PAGES

35-37

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.3677

DOI

http://dx.doi.org/10.1038/nbt.3677

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021422818

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27669166


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