Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing.

Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions.

Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing.

Prime editing recently emerged as a next-generation approach for precise genome editing. Here we exploit DNA double-strand break (DSB) repair to develop two strategies that install precise genomic insertions using an SpCas9 nuclease-based prime editor (PEn). We first demonstrate that PEn coupled to a regular prime editing guide RNA (pegRNA) efficiently promotes short genomic insertions through a homology-dependent DSB repair mechanism.

Interleukin-19 blockade attenuates collagen-induced arthritis in rats.

Objectives: RA is the most common form of inflammatory arthritis. IL-19 acts as a pro-inflammatory cytokine involved in the pathogenesis of RA. We investigated whether anti-IL-19 antibody treatment would modulate the severity of the disease in a CIA rat model.