Abstract
Sequence-specific endonucleases, such as zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas), allow simple generation of genetically modified animals. We utilized ZFNs and TALENs to generate several knockout rat models of human diseases. Furthermore, CRISPR/Cas9 used in conjunction with single-stranded oligodeoxyribonucleotides enabled us to generate several types of targeted knockin animal, such as single nucleotide polymorphism substitution, short DNA fragment integration, and large DNA fragment elimination. These powerful technologies have opened new doors for genome manipulation that enable the engineering of animal models of human disease and potential therapeutic applications.
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