title: Genome engineering with TAL-effector nucleases and alternative modular nuclease technologies.
abstract: Over three years following the discovery of the TAL code, artificial TAL effector DNA binding domains have emerged as the premier platform for building site-specific DNA binding polypeptides for use in biological research. Here, we provide an overview of TAL effector and alternative modular DNA binding domain (mDBD) technologies, focusing on their use in established and emerging architectures for building site-specific endonucleases for genome engineering applications. We also discuss considerations for choosing TAL effector/mDBD or alternative nuclease technologies for genome engineering projects ranging from basic laboratory gene editing of cultured cell lines to therapeutics. Finally, we highlight how the rapid pace of development of mDBD-based, such as monomeric TALENs (I-TevI-TAL), and more recently RNA-guided nucleases (CRISPR-Cas9) has led to a transition in the field of genome engineering towards development of the next generation of technologies aimed at controlling events that occur after targeted DNA breaks are made.
authors.affiliation: University of Washington School of Medicine, Seattle Children's Research Institute, Seattle, WA, USA. scharenberg@cellectis.com.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scharenberg
authors.forename: Philippe
authors.initials: P
authors.lastname: Duchateau
authors.forename: Julianne
authors.initials: J
authors.lastname: Smith
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D000076987:CRISPR-Associated Protein 9; D064130:CRISPR-Associated Proteins / Q000235:genetics*; D064113:CRISPR-Cas Systems; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005818:Genetic Engineering / Q000379:methods*; D015316:Genetic Therapy; D006801:Humans; D015202:Protein Engineering; D000071336:Transcription Activator-Like Effectors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D064130:CRISPR-Associated Proteins; D000071336:Transcription Activator-Like Effectors; D000076987:CRISPR-Associated Protein 9; C000606107:Cas9 endonuclease Streptococcus pyogenes