Rapid, modular and reliable construction of complex mammalian gene circuits
We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonst...
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Veröffentlicht in: | Nucleic acids research 2013-09, Vol.41 (16), p.e156-e156 |
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container_title | Nucleic acids research |
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creator | Guye, Patrick Li, Yinqing Wroblewska, Liliana Duportet, Xavier Weiss, Ron |
description | We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction of synthetic gene circuits of up to 64 kb in size comprising 11 transcription units and 33 basic parts. We show robust gene expression control of multiple transcription units by small molecule inducers in human cells with transient transfection and stable chromosomal integration of these circuits. This framework enables development of complex gene circuits for engineering mammalian cells with unprecedented speed, reliability and scalability and should have broad applicability in a variety of areas including mammalian cell fermentation, cell fate reprogramming and cell-based assays. |
doi_str_mv | 10.1093/nar/gkt605 |
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Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction of synthetic gene circuits of up to 64 kb in size comprising 11 transcription units and 33 basic parts. We show robust gene expression control of multiple transcription units by small molecule inducers in human cells with transient transfection and stable chromosomal integration of these circuits. This framework enables development of complex gene circuits for engineering mammalian cells with unprecedented speed, reliability and scalability and should have broad applicability in a variety of areas including mammalian cell fermentation, cell fate reprogramming and cell-based assays.</description><subject>Bioengineering</subject><subject>Gene Regulatory Networks</subject><subject>Genetic Engineering - methods</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Methods Online</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkVtr3DAQRkVoyW62fekPKH5sQ5yMrrZfCiHkRhYCoX0Wsi67am1pK9kh-ff1ssmS9EmM5sw3DAehLxhOMTT0LKh0tvozCOAHaI6pICVrBPmA5kCBlxhYPUNHOf8GwAxzdohmhNaswgBzdPegNt6cFH00Y6dSoYIpku28ajtb6BjykEY9-BiK6Ka633T2qehV36uJCcXKhgnzSY9-yJ_QR6e6bD-_vAv06-ry58VNuby_vr04X5aaYTKUrtKmgco5UzliKwGuNdQw5qgwjDdME2014S0RxnKCGSOkBlCtaxunVI3pAv3Y5W7GtrdG2zAk1clN8r1KzzIqL993gl_LVXyUtBKUi23A913A-r-xm_Ol3P4BNETwpn7cst9elqX4d7R5kL3P2nadCjaOWWJGoea0buiEHu9QnWLOybp9Nga5NSUnU3JnaoK_vj1ij76qof8Ab8ORHA</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Guye, Patrick</creator><creator>Li, Yinqing</creator><creator>Wroblewska, Liliana</creator><creator>Duportet, Xavier</creator><creator>Weiss, Ron</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope></search><sort><creationdate>20130901</creationdate><title>Rapid, modular and reliable construction of complex mammalian gene circuits</title><author>Guye, Patrick ; Li, Yinqing ; Wroblewska, Liliana ; Duportet, Xavier ; Weiss, Ron</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-f7cd907ffd7f2e760fbd3d44f36d4594c2cec25b26de5214422800abfb9faa813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Bioengineering</topic><topic>Gene Regulatory Networks</topic><topic>Genetic Engineering - methods</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Methods Online</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guye, Patrick</creatorcontrib><creatorcontrib>Li, Yinqing</creatorcontrib><creatorcontrib>Wroblewska, Liliana</creatorcontrib><creatorcontrib>Duportet, Xavier</creatorcontrib><creatorcontrib>Weiss, Ron</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guye, Patrick</au><au>Li, Yinqing</au><au>Wroblewska, Liliana</au><au>Duportet, Xavier</au><au>Weiss, Ron</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid, modular and reliable construction of complex mammalian gene circuits</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2013-09-01</date><risdate>2013</risdate><volume>41</volume><issue>16</issue><spage>e156</spage><epage>e156</epage><pages>e156-e156</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. 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subjects | Bioengineering Gene Regulatory Networks Genetic Engineering - methods HEK293 Cells Humans Life Sciences Methods Online |
title | Rapid, modular and reliable construction of complex mammalian gene circuits |
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