Genome Editing of Structural Variations: Modeling and Gene Correction

Chul-Yong Park, Jin Jea Sung, Dong-Wook Kim, Trends in Biotechnology, Available online 23 March 2016, ISSN 0167-7799, doi:10.1016/j.tibtech.2016.02.011.

Although in vivo gene correction using genetic scissor technology (Meganucleases, ZFNs, TALENs and CRISPR/Cas9) may be available and desirable in the future, effective and cell-specific delivery systems should be developed. These technologies promise to expand our understanding of the mechanism of SVs and our ability to treat SV-related diseases.

For Friedreich's ataxia (FRDA), regions containing GAA repeats from frataxin(FXN) intron 1 were removed by expressing ZFNs targeting 334bp and 896bp upstream of GAA repeats in FRDA fibroblasts and lymphoblasts. The FRDA phenotype was reversed, with increased frataxin expression, when corrected FRDA fibroblasts were converted to iPSCs and differentiated into neurons (Li, Y. et al. (2015)).