Introduction

Genome engineering via programmable nucleases including the CRISPR-Cas system

• - Genome editing in plants, animals, and cultured human cells including iPS/ES cells
• - Engineered nuclease-mediated gene and cell therapy
• - Functional genomics using genome-scale libraries of programmable nucleases

Main research activities

We focus on developing programmable nucleases that enable genome editing in plants, animals, and cultured cells including human pluripotent stem cells. These nucleases cleave chromosomal DNA in a targeted manner, producing DNA double-strand breaks (DSBs), whose repair via endogenous mechanisms gives rise to targeted genome modification in cells and whole organisms. For the last ten years or so, we have developed three different types of programmable nucleases, namely, zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) derived from the type II CRISPR/Cas prokaryotic adaptive immune system. These nucleases are now used widely in almost every discipline in biology, biotechnology, and molecular medicine. We have opened websites to help researchers choose unique RGEN target sites suitable for gene disruption (www.rgenome.net) and TALEN sites in 18,740 protein-coding genes and 274 miRNA sequences in the human genome (www.talenlibrary.net).

We will continue our efforts to improve and expand genome editing technologies. In addition, we plan to use these powerful tools to discover new genes associated with various disease phenotypes such as viral replication and cancer and to develop methods of gene/cell therapy for the treatment of both acquired and genetic diseases. We also focus on developing genome-engineered pigs appropriate for organ transplantation and value-added crops.