ArticleProtein engineering, design & selection : PEDS2012
Improved drug-like properties of therapeutic proteins by directed evolution.
Article in Protein engineering, design & selection : PEDS, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 24 citations in OpenAlex.
- Determination of the optimal connector length to enhance stability of backbone-circularized granulocyte colony-stimulating factor.FEBS open bio · 2023Article
- An in vivo platform to select and evolve aggregation-resistant proteins.Nature communications · 2020Article
- Using protein engineering to understand and modulate aggregation.Current opinion in structural biology · 2020Review
- Surface patches on recombinant erythropoietin predict protein solubility: engineering proteins to minimise aggregation.BMC biotechnology · 2019Article
- Ribosome Display: A Potent Display Technology used for Selecting and Evolving Specific Binders with Desired Properties.Molecular biotechnology · 2019Review
- Calorimetric Study ofJournal of analytical methods in chemistry · 2018Article
- Inducing protein aggregation by extensional flow.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many natural human proteins have functional properties that make them useful as therapeutic drugs. However, not all these proteins are compatible with large-scale manufacturing processes or sufficiently stable to be stored for long periods prior to use. In this study, we focus on small four-helix bundle proteins and employ ribosome display in conjunction with three parallel selection pressures to favour the isolation of variant proteins with improved expression, solubility and stability. This in vitro evolution strategy was applied to two human proteins with known drug development issues, granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO). In the case of G-CSF, the soluble expression levels in Escherichia coli were improved 1000-fold, while for EPO the level of aggregation in an accelerated shelf-life study was reduced from over 80% to undetectable levels. These results exemplify the general utility of our in vitro evolution strategy for improving the drug-like properties of therapeutic proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.