Our Projects
Recent advances in CRISPR-based technologies have revolutionized gene editing and modulation, but their clinical translation is hindered by delivery challenges, off-target effects, and immunogenicity. Small molecules (SMs) and oligonucleotides (ODNs) offer promising alternatives due to their cell permeability, scalability, and potential for precise temporal control. However, achieving selective gene activation or repression using chemical approaches remains a significant unmet challenge. This project aims to develop innovative small-molecule tools to target DNA and RNA for selective gene modulation
RNA Targeting Therapeutic Design
More than 90% of the human genome is transcribed into RNA, which provides vast druggable space compared with protein targeting. RNA’s druggable features include both its single-stranded primary sequence and its complex 3D structures. Though RNA has been involved in various diseases and regarded as a key drug target, however, realizing the full therapeutic potential of RNA requires an in-depth understanding of RNA-drug interactions and the development of novel drug designs for targeting RNA with precision. This project aims to develop novel RNA binders, bifunctional binders and RNA editing approaches for therapeutic applications.
DNA Sequence-Specific Binder Design
Targeting DNA at the genomic level holds promise for gene regulation and disease treatment. Pyrrole-Imidazole Polyamides (PIPs) are leading candidates for sequence-selective DNA binding, but achieving high specificity at the whole-genome scale remains challenging. This project integrates chemical biology, computational chemistry, and AI-driven approaches to design new DNA-binding oligomers, optimizing monomer interactions and flexible linker strategies to achieve precise gene targeting.