In Science this week, two research groups report data suggesting that cytosine base editors can trigger a significant number of off-target mutations. In the first paper, a group of US and Chinese scientists developed a method for detecting off-target mutations in mouse embryos following editing by either CRISPR-Cas9 or adenine or cytosine base editors. They discover a minimal number of single nucleotide variants (SNVs) in CRISPR and adenine base edited cells, but SNVs at 20-fold higher frequencies in cytosine base edited cells. In the second study, a different group of Chinese and US collaborators compared the effects of adenine and cytosine base editors in rice. They, too, find that cytosine base editors — but not adenine base editors — lead to increased genome-wide off-target mutations.
And in Science Translational Medicine, a pair of Stanford University School of Medicine researchers discuss the hurdles facing the widespread adoption of chimeric antigen receptor (CAR) T cell-based cancer immunotherapies. They state that, despite clinical successes with CAR-T cell therapies, issues such as toxicity, target antigen loss-driven relapse, and tumor selection remain key hurdles for the field. They also discuss efforts to use gene editing to design off-the-shelf CAR-T cell therapies with improved properties, which may also help drive down the high costs of such treatments.