Gene-editing researchers reduce cancer risk

A new and safer solution has been worked out by local researchers to tackle with the problem of off-target RNA mutations generated by DNA base editing.

Base editing can help in treatment of rare diseases, but off-target effects bring a risk of cancer.

The study published in “Nature” this week was performed by researchers in Dr. Yang Hui's Lab at the Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, Chinese Academy of Sciences (CAS) with the assistance of two other research teams led by Dr. Li Yixue and Dr. Guo Fan.

This work revealed a previously overlooked aspect of the risk of DNA base editors and provided a solution to the RNA off-target problem by engineering deaminases. 

Yang's team is working on applying DNA base editing to animal models.

Genome editing is one of the most important bioscience techniques. In 2012, scientists discovered that clustered regularly interspaced short palindromic repeats (CRISPR), a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea, are a key part of the immune system — for instance, when a virus infects a bacteria, the bacteria responds by cutting up the virus’s DNA. This discovery led to development of the CRISPR-Cas9 gene editing tool and its associated cancer risk.

Scientists then developed base editors (BEs). DNA base editor BE3 is considered safer than previous ones and became a popular tool in treating diseases like spinal muscular dystrophy and hereditary hearing loss. Following BE3, more DNA base editing methods, such as adenine base editors (ABEs), emerged.

Yang's team found these methods not to be completely safe. After reporting severe BE3 off-target mutations in March, the team noticed a huge amount of off-target RNA mutations as well.

To eliminate this risk, Yang's team engineered the deaminases and prevented them from binding to RNA, which can prevent off-target RNA mutations.