In this week's Nature Medicine, an international research team presents a metagenomic analysis of colorectal cancer datasets, uncovering microbiome biomarkers with clinical potential. The work — which covered 969 fecal metagenomes — revealed a greater richness in the gut microbiome of colorectal cancer patients versus controls and uncovered a number of predictive microbiome signatures. The scientists also find the choline trimethylamine-lyase gene to be overabundant in colorectal cancer, pointing to a relationship between microbiome choline metabolism and the disease. Their findings, the authors write, can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies. GenomeWeb has more on this, here.
And in Nature, a group from the University of Massachusetts Medical School describes a method for therapeutic gene correction that requires a simple nuclease-induced DNA double-strand break. While other nuclease-based gene-editing approaches such as CRISPR-Cas9 require the co-delivery of an exogenous DNA donor to recode a disease-causing sequence, the research team shows that pathogenic frameshift mutations resulting from microduplications can be efficiently reverted to the wildtype sequence by generating a DNA double-stranded break near the centre of the duplication. They demonstrate their finding in patient-derived cell lines for two diseases — limb-girdle muscular dystrophy type 2G and Hermansky–Pudlak syndrome type 1 — and state that their approach is broadly applicable to a wide range of microduplication lengths and can be initiated by a variety of nucleases.
Meanwhile, in Nature Structural & Molecular Biology, a University of California, Berkeley-led team reports the identification of enzymes that can block CRISPR-Cas12a genome editing. The three so-called anti-CRISPRs (Acrs), which bacteria use to defeat CRISPR-based adaptive immune systems, were shown to work in different ways: two of them by inhibiting the recognition of double-stranded DNA, and the other triggering cleavage of the target-recognition sequence of the Cas12a-bound guide RNA to irreversibly inactivate the Cas12a complex. "These mechanistic insights reveal vulnerabilities in the modes of Cas12a targeting, providing scope for greater control of a rapidly expanding landscape of Cas12a and Acr applications," the authors say.