Programmable nucleases for genome editing

Programmable nucleases for genome editing. From Carroll (2014) Annu. Rev. Biochem. 83: 409.

Model of a pair of ZFNs bound to DNA.

Model of a pair of ZFNs bound to DNA. From Smith et al. (2000) Nucleic Acids Res. 28: 3361.

Illustration of the consequences of targeted genome cleavage

Illustration of the consequences of targeted genome cleavage. After nuclease cleavage at a unique site (red lightning bolt), cells repair the break, sometimes inaccurately (NHEJ), or by copying a template (HDR). From Carroll and Charo (2015) Genome Biol. 16: 242.


Genome Editing

We work with the powerful, exciting and relatively new tools of precise genome engineering, using the ZFN, TALEN and CRISPR-Cas platforms. This technology, also called genome editing or gene editing, allows researchers to make specific, targeted changes at unique sites in the genomic DNA of essentially any cell or organism. To date the nuclease platforms have been used successfully to modify the genomes of more than 60 different organisms, from model species to crop plants to primates.

Much of our past work involved evaluating how nuclease-mediated genome modification works, with the goal of optimizing procedures and enhancing desired. Currently we are interested in other aspects of how the nucleases function and how the repair outcomes may be limited. In addition, we are collaborating with other groups on applications to human cells and potential clinical uses. We remain open to additional collaborations where our expertise and experience may be useful. 

I am personally interested in the broader uses of genome editing and the societal implications of such uses. For example, this powerful technology offers many opportunities for improving food organisms, both crop plants and livestock. Medical applications of genome editing are in their infancy, but also have great promise. We want to ensure that such uses are developed safely and their benefits are distributed appropriately. Complex ethical and societal issues are raised by these prospects, particularly when modifications to the human germline are considered.