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Article: Reprogramming cells with synthetic proteins

TitleReprogramming cells with synthetic proteins
Authors
Keywordsprotein design
cellular reprogramming
protein engineering
synthetic transcription factors
transactivation
Issue Date2015
Citation
Asian Journal of Andrology, 2015, v. 17, n. 3, p. 394-402 How to Cite?
Abstract© 2015 AJA, SIMM & SJTU. All rights reserved 1008-682X. Conversion of one cell type into another cell type by forcibly expressing specific cocktails of transcription factors (TFs) has demonstrated that cell fates are not fixed and that cellular differentiation can be a two-way street with many intersections. These experiments also illustrated the sweeping potential of TFs to "read" genetically hardwired regulatory information even in cells where they are not normally expressed and to access and open up tightly packed chromatin to execute gene expression programs. Cellular reprogramming enables the modeling of diseases in a dish, to test the efficacy and toxicity of drugs in patient-derived cells and ultimately, could enable cell-based therapies to cure degenerative diseases. Yet, producing terminally differentiated cells that fully resemble their in vivocounterparts in sufficient quantities is still an unmet clinical need. While efforts are being made to reprogram cells nongenetically by using drug-like molecules, defined TF cocktails still dominate reprogramming protocols. Therefore, the optimization of TFs by protein engineering has emerged as a strategy to enhance reprogramming to produce functional, stable and safe cells for regenerative biomedicine. Engineering approaches focused on Oct4, MyoD, Sox17, Nanog and Mef2c and range from chimeric TFs with added transactivation domains, designer transcription activator-like effectors to activate endogenous TFs to reprogramming TFs with rationally engineered DNA recognition principles. Possibly, applying the complete toolkit of protein design to cellular reprogramming can help to remove the hurdles that, thus far, impeded the clinical use of cells derived from reprogramming technologies.
Persistent Identifierhttp://hdl.handle.net/10722/253165
ISSN
2023 Impact Factor: 3.0
2023 SCImago Journal Rankings: 0.689
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, Xiaoxiao-
dc.contributor.authorMalik, Vikas-
dc.contributor.authorJauch, Ralf-
dc.date.accessioned2018-05-11T05:38:47Z-
dc.date.available2018-05-11T05:38:47Z-
dc.date.issued2015-
dc.identifier.citationAsian Journal of Andrology, 2015, v. 17, n. 3, p. 394-402-
dc.identifier.issn1008-682X-
dc.identifier.urihttp://hdl.handle.net/10722/253165-
dc.description.abstract© 2015 AJA, SIMM & SJTU. All rights reserved 1008-682X. Conversion of one cell type into another cell type by forcibly expressing specific cocktails of transcription factors (TFs) has demonstrated that cell fates are not fixed and that cellular differentiation can be a two-way street with many intersections. These experiments also illustrated the sweeping potential of TFs to "read" genetically hardwired regulatory information even in cells where they are not normally expressed and to access and open up tightly packed chromatin to execute gene expression programs. Cellular reprogramming enables the modeling of diseases in a dish, to test the efficacy and toxicity of drugs in patient-derived cells and ultimately, could enable cell-based therapies to cure degenerative diseases. Yet, producing terminally differentiated cells that fully resemble their in vivocounterparts in sufficient quantities is still an unmet clinical need. While efforts are being made to reprogram cells nongenetically by using drug-like molecules, defined TF cocktails still dominate reprogramming protocols. Therefore, the optimization of TFs by protein engineering has emerged as a strategy to enhance reprogramming to produce functional, stable and safe cells for regenerative biomedicine. Engineering approaches focused on Oct4, MyoD, Sox17, Nanog and Mef2c and range from chimeric TFs with added transactivation domains, designer transcription activator-like effectors to activate endogenous TFs to reprogramming TFs with rationally engineered DNA recognition principles. Possibly, applying the complete toolkit of protein design to cellular reprogramming can help to remove the hurdles that, thus far, impeded the clinical use of cells derived from reprogramming technologies.-
dc.languageeng-
dc.relation.ispartofAsian Journal of Andrology-
dc.subjectprotein design-
dc.subjectcellular reprogramming-
dc.subjectprotein engineering-
dc.subjectsynthetic transcription factors-
dc.subjecttransactivation-
dc.titleReprogramming cells with synthetic proteins-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4103/1008-682X.145433-
dc.identifier.pmid25652623-
dc.identifier.scopuseid_2-s2.0-84928998150-
dc.identifier.volume17-
dc.identifier.issue3-
dc.identifier.spage394-
dc.identifier.epage402-
dc.identifier.eissn1745-7262-
dc.identifier.isiWOS:000354130800007-
dc.identifier.issnl1008-682X-

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