Abstract:
:RNA-interference (RNAi) is a potent mechanism, conserved from plants to humans for specific silencing of genes, which holds promise for functional genomics and gene-targeted therapies. Here we show that bacteria engineered to produce a short hairpin RNA (shRNA) targeting a mammalian gene induce trans-kingdom RNAi in vitro and in vivo. Nonpathogenic Escherichia coli were engineered to transcribe shRNAs from a plasmid containing the invasin gene Inv and the listeriolysin O gene HlyA, which encode two bacterial factors needed for successful transfer of the shRNAs into mammalian cells. Upon oral or intravenous administration, E. coli encoding shRNA against CTNNB1 (catenin beta-1) induce significant gene silencing in the intestinal epithelium and in human colon cancer xenografts in mice. These results provide an example of trans-kingdom RNAi in higher organisms and suggest the potential of bacteria-mediated RNAi for functional genomics, therapeutic target validation and development of clinically compatible RNAi-based therapies.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Xiang S,Fruehauf J,Li CJdoi
10.1038/nbt1211subject
Has Abstractpub_date
2006-06-01 00:00:00pages
697-702issue
6eissn
1087-0156issn
1546-1696pii
nbt1211journal_volume
24pub_type
杂志文章abstract::Organophosphorus hydrolase (OPH) was displayed and anchored onto the surface of Escherichia coli using an Lpp-OmpA fusion system. Production of the fusion proteins in membrane fractions was verified by immunoblotting with OmpA antisera. Inclusion of the organophosphorus hydrolase signal sequence was necessary for achi...
journal_title:Nature biotechnology
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pub_type: 杂志文章,评审
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abstract::We present a technology to screen millions of B cells for natively paired human antibody repertoires. Libraries of natively paired, variable region heavy and light (VH:VL) amplicons are expressed in a yeast display platform that is optimized for human Fab surface expression. Using our method we identify HIV-1 broadly ...
journal_title:Nature biotechnology
pub_type: 杂志文章
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更新日期:2018-02-01 00:00:00
abstract::L-Ascorbic acid (vitamin C) in fruits and vegetables is an essential component of human nutrition. Surprisingly, only limited information is available about the pathway(s) leading to its biosynthesis in plants. Here, we report the isolation and characterization of GalUR, a gene from strawberry that encodes an NADPH-de...
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更新日期:2003-02-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章,已发布勘误
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更新日期:2000-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/nbt.1611
更新日期:2010-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/nbt0697-564
更新日期:1997-06-01 00:00:00
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