Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction.
basic_science · Level V
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- Record sourced from PubMed, PMID 27669166.
- Also identified by DOI 10.1038/nbt.3677 and PMC identifier 5225049.
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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.
Medical subject headings
- Conserved Sequence
- Drug Discovery
- Drug Synergism
- Factor VIII
- Protein Engineering
- Proteins