Abstract：
:Evolution of eukaryotes is mediated by sexual recombination of parental genomes. Crossovers occur in random, but homologous, positions at a frequency that depends on DNA length. As exons occupy only 1% of the human genome and introns about 24%, by far most of the crossovers occur between exons, rather than inside. The natural process of creating new combinations of exons by intronic recombination is called exon shuffling. Our group is developing in vitro formats for exon shuffling and applying these to the directed evolution of proteins. Based on the splice frame junctions, nine classes of exons and three classes of introns can be distinguished. Splice frame diagrams of natural genes show how the splice frame rules govern exon shuffling. Here, we review various approaches to constructing libraries of exon-shuffled genes. For example, exon shuffling of human pharmaceutical proteins can generate libraries in which all of the sequences are fully human, without the point mutations that raise concerns about immunogenicity.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Kolkman JA,Stemmer WPdoi
10.1038/88084subject
Has Abstractpub_date
2001-05-01 00:00:00pages
423-8issue
5eissn
1087-0156issn
1546-1696pii
88084journal_volume
19pub_type
杂志文章,评审abstract：:We describe protein interaction quantitation (PIQ), a computational method for modeling the magnitude and shape of genome-wide DNase I hypersensitivity profiles to identify transcription factor (TF) binding sites. Through the use of machine-learning techniques, PIQ identified binding sites for >700 TFs from one DNase ...
journal_title：Nature biotechnology
pub_type： 杂志文章
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abstract：:Purging of tumor cells and selection of stem cells are key technologies for enabling stem cell transplantation and stem cell gene therapy. Here we report a strategy for cell selection based on physical properties of the cells. Exposing cells to an external pulsed electric field (PEF) increases the natural potential di...
journal_title：Nature biotechnology
pub_type： 杂志文章
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journal_title：Nature biotechnology
pub_type： 杂志文章
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journal_title：Nature biotechnology
pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：1999-07-01 00:00:00
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更新日期：2002-04-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2000-11-01 00:00:00
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更新日期：2013-04-01 00:00:00
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doi：10.1038/nbt.2768
更新日期：2013-12-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2195
更新日期：2012-05-13 00:00:00
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journal_title：Nature biotechnology
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doi：10.1038/nbt0396-303
更新日期：1996-03-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1300
更新日期：2007-05-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-020-0412-8
更新日期：2020-04-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/74531
更新日期：2000-04-01 00:00:00
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更新日期：2003-02-01 00:00:00
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pub_type：
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更新日期：2003-03-01 00:00:00
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journal_title：Nature biotechnology
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更新日期：2001-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：1998-07-01 00:00:00
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更新日期：2012-06-24 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
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更新日期：2007-11-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 杂志文章
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更新日期：2017-09-01 00:00:00
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journal_title：Nature biotechnology
pub_type： 评论,社论
doi：10.1038/nbt0909-777
更新日期：2009-09-01 00:00:00
