A team of researchers from Massachusetts General Hospital have developed a new Cas9 variant that virtually eliminates the reliance on protospacer adjacent motifs (PAM) in CRISPR-based genome editing. The recognition of PAM sequences by Cas enzymes is required for successful cleavage of target DNA in CRISPR systems, but constrains targeting and affects editing efficiency and flexibility. To address this limitation, the scientists engineered variants of the canonical Streptococcus pyogenes Cas9 to create a variant capable of targeting an expanded set of PAM sequences, which they optimized into a near-PAMless variant dubbed SpRY. SpRY can target almost all PAMs, they write, and is used to generate previously inaccessible disease-relevant genetic variants. GenomeWeb has more on this, here.
A genome-scale, open-source atlas of human metabolism is presented in Science Signaling this week. An international team led by scientists from the Chalmers University of Technology integrated and curated recent genome-scale metabolic models to create a consensus model called Human1. They use their model to compare metabolic network structure and function across different healthy tissue and tumor types, and to predict genes essential for metabolic tasks in human cells, among other things. The researchers also built an accompanying web portal to facilitate further exploration and visualization of Human1 content.