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This Week in Cell: Sep 12, 2013

The Massachusetts Institute of Technology's Rudolf Jaenisch and colleagues report on a genome editing approach that takes advantage of a type II bacterial CRISPR/CAS system. By directing messenger RNA from the Cas9 gene to genomic sequences of interest with the help of single-guided RNAs, the researchers demonstrated that they could generate mice carrying fluorescent tags or conditional mutations at several genes in a single step. Their follow-up experiments in engineered mice or embryonic stem cell lines suggest the type II CRISPR/CAS method infrequently introduces off-target alterations.

In another Cell study, an independent team led by investigators at the Broad Institute describes a CRISPR/CAS-based genome editing strategy that involves a mutant version of Cas9 as well as so-called double nicking at targeted DNA sites. In their own cell line and mouse zygote experiments, authors of this study saw dips in off-target activity that ranged from around 50-fold to around 1,000-fold. "Because individual nicks in the genome are repaired with high fidelity," they say, "simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and thus effectively extends the number of specifically recognized bases for target cleavage."

Finally, researchers from the Broad Institute, Vanderbilt University, and Columbia University introduce an interactive, online resource for targeting small molecules to specific cancer lines or mutations. The team developed the Cancer Therapeutics Response Portal, or CTRP, site by looking at the sensitivity of 242 cancer cell lines with known genomic profiles treated with more than 350 small molecules. In the process, investigators uncovered a range of interactions, including genetic glitches that could serve as possible small molecule targets in cancer. "The resource can be used to develop novel therapeutic hypotheses," they note, "and to accelerate discovery of drugs matched to patients by their cancer genotype and lineage."