CRISPR: No Sign of Slowing Down

Just 5 years after its first demonstration as a genome editing tool, CRISPR is pretty much a household name. From its humble beginnings as a way for bacteria to chop up invading viral DNA, CRISPR has taken over our discussions of animal models, high-throughput screens, GMOs, and gene therapy—even biomedical ethics and scientific patent law—all at breakneck speed. While CRISPR is not without its drawbacks, it has major advantages in that it is programmable and applicable to countless organisms, cell types, and research questions. With over 2,500 CRISPR papers published already in 2018, it’s easy to wonder whether there is anything truly new left under the sun. With CRISPR-mediated genome editing, the CRISPR enzyme makes a cut at the site specified by its guide RNA, and cellular repair processes take over to fix the DNA lesion, often introducing small insertions and deletions or stimulating homologous recombination at the site. This process leads to editing of the DNA sequence, allowing scientists to create point mutations; engineer nucleotide substitutions in regulatory regions; insert tags or reporter genes; or delete exons, genes, or sets of genes, for example. Now, two studies from the labs of Zhongjun Qin and Jef Boeke push the technology to its limits by using CRISPR to fuse entire yeast chromosomes together. Qin and colleagues took advantage of yeast’s superior homologous recombination efficiency to create one single, fused chromosome out of the native 16. Remarkably, the single-chromosome yeast cells had very similar cell growth and transcriptome to wild-type yeast (Shao et al., 2018). In the study by Boeke and colleagues, the authors fused yeast chromosomes to create a two-chromosome yeast strain that is reproductively isolated from wild-type yeast, opening up the question of whether it can be classified as a separate species. Similar to the related paper, they also observed that the yeast cells with this drastically altered karyotype were viable with only slightly reduced growth rate (Luo et al., 2018). Moving CRISPR technology from gene editing to karyotype engineering