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• W2799720186 endingPage "20170077" @default.
• W2799720186 startingPage "20170077" @default.
• W2799720186 abstract "The ability to target DNA specifically at any given position within the genome allows many intriguing possibilities and has inspired scientists for decades. Early gene-targeting efforts exploited chemicals or DNA oligonucleotides to interfere with the DNA at a given location in order to inactivate a gene or to correct mutations. We here describe an example towards correcting a genetic mutation underlying Pompe's disease using a nucleotide-fused nuclease (TFO-MunI). In addition to the promise of gene correction, scientists soon realized that genes could be inactivated or even re-activated without inducing potentially harmful DNA damage by targeting transcriptional modulators to a particular gene. However, it proved difficult to fuse protein effector domains to the first generation of programmable DNA-binding agents. The engineering of gene-targeting proteins (zinc finger proteins (ZFPs), transcription activator-like effectors (TALEs)) circumvented this problem. The disadvantage of protein-based gene targeting is that a fusion protein needs to be engineered for every locus. The recent introduction of CRISPR/Cas offers a flexible approach to target a (fusion) protein to the locus of interest using cheap designer RNA molecules. Many research groups now exploit this platform and the first human clinical trials have been initiated: CRISPR/Cas has kicked off a new era of gene targeting and is revolutionizing biomedical sciences. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’." @default.
• W2799720186 created "2018-05-17" @default.
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• W2799720186 date "2018-04-23" @default.
• W2799720186 modified "2023-09-27" @default.
• W2799720186 title "The past and presence of gene targeting: from chemicals and DNA via proteins to RNA" @default.
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• W2799720186 doi "https://doi.org/10.1098/rstb.2017.0077" @default.

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