DISCOVER-Seq+ is a new method to improve in vivo CRISPR off-target detection sensitivity. Compared with previous methods, the technique can discover up to fivefold more CRISPR off-target sites in immortalised cell lines, primary human cells and mice. DISCOVER-Seq+ works by inhibition of DNA-dependent protein kinase catalytic subunit. This leads to the accumulation of the repair protein MRE11 at CRISPR-Cas-targeted sites, enabling high-sensitivity mapping of off-target sites to positions of MRE11 binding using chromatin immunoprecipitation followed by sequencing. You can read more about DISCOVER-Seq+ in this News & Views article.
In the business of base editors: Evolution from bench to bedside. This review provides an overview of the mechanics of base editing and its use in clinical trials. In addition, the piece elaborates on the recent developments around Vertex and CRISPR Therapeutics' first-in-modality genome-editor exa-cel for the treatment of two haemoglobinopathies that has entered the regulatory spotlight.
A review of CRISPR-based advances in dermatological diseases. This review introduces the adoption of CRISPR technology to study different skin disorders, including monogenic genodermatoses, inflammatory conditions, and cutaneous infections. It highlights the promising preclinical results of CRISPR-mediated treatment and important mechanic discoveries in investigative studies.
Gene therapy for paediatric homozygous familial hypercholesterolaemia. The review discusses this issue in the paediatric patient group with severe compound heterozygous or homozygous null variants associated with aggressive early-onset atherosclerosis and myocardial infarction, along with the critical preclinical studies that use genomic editing strategies to treat HoFH in place of apheresis and liver transplantation.
Last Wednesday, just before Easter, we brought the latest CRISPR clinical trial updates from Caribou Biosciences. The company's second gene-edited CAR-T cell therapy candidate, CB-011, has entered the clinic for multiple myeloma. At the same time, dose expansion is set to commence for its frontrunner candidate CB-010, which is being developed to treat non-Hodgkin lymphoma.
To get more of the CRISPR Medicine News delivered to your inbox, sign up to the free weekly CMN Newsletter here.