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.
Keywords: DNA repair, double strand break, exonuclease, genome engineering, homing endonuclease, meganuclease, nuclease,
TALEN, ZFN, zinc finger nuclease.
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