People--Hangzhou Institute of Medicine Chinese Academy of Sciences

Biography

Dr. Yajun Wang obtained her Ph.D. in Chemistry from the University of British Columbia, Canada. She then completed her Postdoctoral training under the supervision of Dr. John Chapat from the University of California, Irvine. She started her own lab in Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, in May 2022.

Research Interests

My major interest of research has been focused at the interface of chemical and synthetic biology to (1) fundamentally explore the chemical biology of non-natural nucleic acids, which include nucleobase modified nucleic acids with expanded functionalities, Xeno Nucleic Acids (XNA) with artificial sugar backbones, and modified mRNA molecules with non-canonical nucleobases, and (2) to promote the development of non-natural nucleic acid based medicines and biotechnologies. Specifically, we have been intensively working on these projects:

o Exploring the fundamental chemical biology of non-natural nucleic acids

o Expanding the catalytic repertoire of XNA enzymes beyond RNA cleavage and ligation by in vitro selection and evolution.

o Exploring the transition of life’s primitive genetic polymers through the possible mechanism of genetic takeover. We undertake parallel selections for the same RNA cleavage reaction using DNA, RNA, FANA, and threose nucleic acid (TNA): enriched libraries with activities have been sequenced, gene-array based high-throughput activity characterization, bioinformatics and AI facilitated comprehensive sequence analysis are underway

o Improving the functional repertoire, activity, and biostability of functional non-natural nucleic acids through the combinatorial use of chemical modification of nucleobase and sugar backbone

o Molecular design of ASO-like DNAzymes for potent gene silencing of high target and site specificity

o Exploring the intracellular gene silencing activity of intensively modified RNase A mimic DNAzymes

o Developing chemically modified aptamers with covalent ligand binding activities via post-SELEX modification and modified-SELEX

o Screening, synthetic evolution and engineering of nucleic acid processing protein enzymes for the efficient manipulation of non-natural nucleic acids

o Evolving T7 RNA polymerase (T7 RNAP) for highly efficient in vitro transcription of modified mRNA comprising multiple non-canonical nucleotides for alleviated immune stimulation and enhanced translation

Selected Publications

1. Liu, Y., Wang, J., Wu, Y. & Wang, Y. Advancing the enzymatic toolkit for 2′-fluoro arabino nucleic acid (FANA) manipulation: phosphorylation, ligation, replication, and templating RNA transcription. Chem. Sci. 15, 12534–12542 (2024).

Liu, Y. & Wang, Y. Making nucleic acid monomers. Nat. Chem. 14, 725–727 (2022).

Wang, Y., Nguyen, K., Spitale, R. C. & Chaput, J. C. A biologically stable DNAzyme that efficiently silences gene expression in cells. Nat Chem 13, 319–326 (2021).

Nguyen, K., Wang, Y., England, W. E., Chaput, J. C. & Spitale, R. C. Allele-Specific RNA Knockdown with a Biologically Stable and Catalytically Efficient XNAzyme. J. Am. Chem. Soc. 143, 4519–4523 (2021).