Wensheng Wei - Gene Editing and Beyond

The Wei lab focuses on developing novel gene editing tools，investigating high-throughput functional genomics and establishing novel platforms for nucleic acid therapeutics. Based on gene editing technology, they pioneered a series of novel high-throughput functional screening platforms to systematically analyze the function of protein-coding genes, non-coding RNAs, non-coding regulatory elements, and critical amino acids. These platforms include: (1) the CRISPR-based high-throughput screening technology, (2) lncRNA screening methods based on the large-fragment deletion and splice site-targeting strategies, (3) the iBAR strategy and the following BARBEKO method that enhance the efficiency and cost-effectiveness of genome-wide functional screening, (4) the PASTMUS method for scanning and identifying functional sites of proteins at amino acid resolution, and (5) the genome-wide functional amino acid mapping using ABE system. In the field of developing gene editing tools, they firstly developed a novel RNA editing technology named LEAPER and an optimized version LEAPER 2.0, which only requires the introduction of a specially designed "guide" RNA that can recruit the endogenous deaminase ADAR to achieve efficient and precise editing of specific adenosine residues on the target RNA. They further developed an efficient mitochondrial base editor called mitoBE, which has the potential to correct the majority of mitochondrial pathogenic mutations, offering an efficient and precise DNA editing tool for the treatment of mitochondrial genetic diseases. Moreover, they established an efficient in vitro technology platform for the production of high-purity circular RNA, and developed the first circular RNA vaccine against SARS-CoV-2 and its variants.