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."