Sidi Chen

Typically, many genetic changes are required before cancer develops. Approximately 5%–10% of cancers are due to inherited genetic defects from a person's parents, and it is completely random. A single base change can create a devastating genetic disorder or a beneficial adaptation, or it might have no effect at all. How do mutations happen, how do they influence human health, and which one would lead to cancer? These are the key unanswered questions in cancer research.

Sidi Chen, an assistant professor from the Department of Genetics & Systems Biology Institute at Yale University, has been challenging existing paradigms with highly innovative work. Recently, he and his team performed the first in vivo CRISPR screening to discover metastasis drivers, and developed an AAV-based direct in vivo autochthonous CRISPR screening system to identify causative co-drivers in deadly cancers such as glioblastoma and hepatocellular carcinoma. His research can help to develop personalized cancer drugs and treatments, as well as support research into the way cancer develops and spreads. This would be vital to developing precision-based treatment methods.

Chen and his team also developed a system for efficient generation of chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) with considerably enhanced features using streamlined genome engineering. By leveraging trans-activating CRISPR RNA-independent CRISPR–Cpf1 systems with adeno-associated virus (AAV), they were able to build a stable CAR-T cell with homology-directed-repair knock-in and immune-checkpoint knockout at high efficiency in one step. The modularity of the AAV–Cpf1 KIKO system enables a flexible and highly efficient generation of double knock-in of two different CARs in the same T cell. This versatile system opens new capabilities of T-cell engineering with simplicity and precision.

In the future, Chen and his team at Yale will strive to create new and potentially transformative tools and research to tackle cancer and improve treatment methods. They also plan to delve deeper into gene editing, cancer genetics, and high throughput screening to advance transformative science and technology, with the long-term goal of making breakthroughs that can benefit patients.