Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction

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 molecu...

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Detalles Bibliográficos
Autores principales: Zakas, Philip M., Brown, Harrison C., Knight, Kristopher, Meeks, Shannon L., Spencer, H. Trent, Gaucher, Eric A., Doering, Christopher B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225049/
https://www.ncbi.nlm.nih.gov/pubmed/27669166
http://dx.doi.org/10.1038/nbt.3677
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author Zakas, Philip M.
Brown, Harrison C.
Knight, Kristopher
Meeks, Shannon L.
Spencer, H. Trent
Gaucher, Eric A.
Doering, Christopher B.
author_facet Zakas, Philip M.
Brown, Harrison C.
Knight, Kristopher
Meeks, Shannon L.
Spencer, H. Trent
Gaucher, Eric A.
Doering, Christopher B.
author_sort Zakas, Philip M.
collection PubMed
description 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. biosynthesis potential, and reduced inhibition by clinical anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence.
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spelling pubmed-52250492017-03-26 Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction Zakas, Philip M. Brown, Harrison C. Knight, Kristopher Meeks, Shannon L. Spencer, H. Trent Gaucher, Eric A. Doering, Christopher B. Nat Biotechnol Article 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. biosynthesis potential, and reduced inhibition by clinical anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence. 2016-09-26 2017-01 /pmc/articles/PMC5225049/ /pubmed/27669166 http://dx.doi.org/10.1038/nbt.3677 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Zakas, Philip M.
Brown, Harrison C.
Knight, Kristopher
Meeks, Shannon L.
Spencer, H. Trent
Gaucher, Eric A.
Doering, Christopher B.
Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title_full Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title_fullStr Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title_full_unstemmed Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title_short Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
title_sort enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225049/
https://www.ncbi.nlm.nih.gov/pubmed/27669166
http://dx.doi.org/10.1038/nbt.3677
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