ArticleNature biotechnology2002
Growth factor engineering by degenerate homoduplex gene family recombination.
Article in Nature biotechnology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 73 citations in OpenAlex.
- Improved CRISPR genome editing using small highly active and specific engineered RNA-guided nucleases.Nature communications · 2021Article
- From nature to nurture: Essence and methods to isolate robust methanotrophic bacteria.Synthetic and systems biotechnology · 2020Article
- Engineering growth factors for regenerative medicine applications.Acta biomaterialia · 2016Review
- Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently.Chemical Society reviews · 2015Review
- Vector design Tour de Force: integrating combinatorial and rational approaches to derive novel adeno-associated virus variants.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Engineered epidermal growth factor mutants with faster binding on-rates correlate with enhanced receptor activation.FEBS letters · 2011Article
- Golden gate shuffling: a one-pot DNA shuffling method based on type IIs restriction enzymes.PloS one · 2009Article
- GLUE-IT and PEDEL-AA: new programmes for analyzing protein diversity in randomized libraries.Nucleic acids research · 2008Article
- Revealing biases inherent in recombination protocols.BMC biotechnology · 2007Article
- Development of innovative pediocin PA-1 by DNA shuffling among class IIa bacteriocins.Applied and environmental microbiology · 2007Article
- Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Laboratory-directed protein evolution.Microbiology and molecular biology reviews : MMBR · 2005Review
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is great interest in engineering human growth factors as potential therapeutic agonists and antagonists. We approached this goal with a synthetic DNA recombination method. We aligned a pool of "top-strand" oligonucleotides incorporating polymorphisms from mammalian genes encoding epidermal growth factor (EGF) using multiple polymorphic "scaffold" oligonucleotides. Top strands were then linked by gap filling and ligation. This approach avoided heteroduplex annealing in the linkage of highly degenerate oligonucleotides and thus achieved completely random recombination. Cloned genes from a human-mouse chimeric library captured every possible permutation of the parental polymorphisms, creating an apparently complete recombined gene-family library, which has not been previously described. This library yielded a chimeric protein whose agonist activity was enhanced 123-fold. A second library from five mammalian EGF homologs possessed the highest reported recombination density (1 crossover per 12.4 bp). The five-homolog library yielded the strongest-binding hEGF variant yet reported. In addition, it contained strongly binding EGF variants with antagonist properties. Our less biased approach to DNA shuffling should be useful for the engineering of a wide variety of 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.