Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. The 3272–26AG and 3849+10kbCT CFTR mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and the Acidaminococcus sp. BV3L6, AsCas12a. This genetic repair strategy is highly precise, showing very strong discrimination between the wild-type and mutant sequence and a complete absence of detectable off-targets. The efficacy of this gene correction strategy is verified in intestinal organoids and airway epithelial cells derived from CF patients carrying the 3272–26AG or 3849+10kbCT mutations, showing efficient repair and complete functional recovery of the CFTR channel. These results demonstrate that allele-specific genome editing with AsCas12a can correct aberrant CFTR splicing mutations, paving the way for a permanent splicing correction in genetic diseases.

Expanded genetic alphabet could allow for the production of new protein-based drugs.

A study of 8,000 years of genetics from Spain and Portugal yields a surprisingly complex picture of the inhabitants’ ancestry.

Two known gene mutations induce pathways that enhance pancreatic cancer’s ability to invade tissues and evade the immune system. Researchers report the molecular details of this process, providing insights into druggable targets for immunotherapies.

Mutations in the genes KRAS and TP53 are closely linked to pancreatic ductal adenocarcinoma, by far the most common type of pancreatic cancer. Pancreatic cancers are often already malignant when diagnosed, making its five-year survival rate extremely low—less than ten percent. So, understanding how it evolves at the molecular level could help anti-cancer drug development.

Hisataka Sabe of Hokkaido University and colleagues in Japan conducted tests in human cancer cells and in mouse models of the disease to investigate the roles of KRAS and TP53 gene mutations in pancreatic ductal adenocarcinoma. The study was published in the journal Proceedings of the National Academy of Sciences (PNAS).