The functional exploration of genes has always been an important part of the research in the field of life science. When the human genome project decoded the genetic information of all genomes, it was very necessary to establish an efficient high-throughput functional screening platform to quickly establish the relationship between genes and functions. In recent years, genome-editing techniques like CRISPR-Cas9 have made functional screening based on gene knockout possible.
During his Ph.D., Shiyou Zhu first established a high-throughput functional screening methodology for protein-coding and non-coding gene RNA based on the CRISPR-Cas9 system. His predecessors, Zhang Feng and George Church, in the field of gene editing, established the first gene knockout functional screening in mammalian cells in the same period. This genetic tool completely changed gene function research. The process used to screen targets, biomarkers, and other genes that play important roles in drug development. In addition, he collaborated with Xiaole Shirley Liu's group at Harvard University to develop the world ’s first reported one screening methodology about knockout of non-coding RNA.
After that, Shiyou Zhu completed the optimization and application of the high-throughput functional screening methodology based on the CRISPR-Cas9 system. The iBAR-based CRISPR screening methodology developed by Zhu has the same number of cells required to achieve the same effect and data quality. Reducing the original to 1/35, for the first time, he changed the traditional technical route of CRISPR screening.
In July 2019, Shiyou Zhu published his research paper titled "Programmable RNA editing by recruiting proven ADAR using engineered RNAs" online in Nature Biotechnology as the co-first author; reporting, for the first time, a new RNA single-base editing technology called LEAPER.
Using this technique, the researchers were able to edit transcripts of a range of disease-related genes efficiently and accurately. The establishment of LEAPER gene-editing technology provides a new tool for the basic research of life science, and also shows great potential in the field of gene repair and disease treatment.
Regarding his plans for the next stage, Shiyou Zhu said that he will continue his studies at MIT. The goal is to continue to develop new and safer genome editing tools and a high-throughput omics research platform combining genome editing. "I hope that my research results will lead to clinical trials of complex diseases in the future."