In this week's Science, a multi-institute team publishes a study revealing new details about how the DNA-cutting protein used in the genome-editing technology CRISPR/Cas9 effectively ignores off-target sites. Although the protein's specificity was well known, the mechanisms behind its effect were not. The researchers used time-lapsed single-molecule imaging to track Cas9 in vivo, and used the data to calculate the likelihood that Cas9 would remain in one place. They found that the protein spends very little time on non-target gene sequences and that it travels more slowly through dense heterochromatic regions of DNA, although it retains the ability to bind to targets in these regions.
And in Science Translational Medicine, a research group led by scientists from the Institute of Cancer Research in London reports data showing that resistance to hormone therapy occurs in the later stages of breast cancer, not the earlier ones, suggesting that early treatment may help avoid resistance. Estrogen receptor-positive breast cancer can be treated with estrogen suppressors, but mutations in the estrogen receptor gene ESR1 could allow a tumor to resist such therapy. The investigators analyzed ESR1 mutations in circulating tumor DNA in blood samples from 171 women with advanced breast cancer, discovering that none of those who received hormone therapy had ESR1 mutations prior to treatment. Such mutations did not appear to develop in cases with hormonal therapy initiated during the first course of treatment, but appeared frequently in those treated once the cancer had already spread.