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RESEARCH

More than 7,000 orphan diseases have been reported, with approximately 80% caused by mutations in a single gene. Beyond rare disorders, monogenic defects also contribute to common conditions such as familial hypercholesterolemia, cystic fibrosis, and certain forms of diabetes and cancer. Growing evidence demonstrates that selectively correcting key disease-driving genes can offer profound therapeutic benefits. However, clinical translation remains limited due to challenges such as undruggable protein targets, acquired drug resistance, and a lack of efficient strategies for gene-specific intervention. To address these unmet needs, our lab develops gene-selective chemical approaches that directly target DNA and RNA to modulate transcription and translation, offering new avenues for precision therapeutics. Our research is guided by the following key questions:

Which genes drive disease?

How can we control gene expression by chemically targeting DNA and RNA?

How can innovative designs and strategies enhance nucleic acid binders?

By designing novel nucleic acid binders—such as small molecules and antisense oligonucleotides—we aim to achieve selective gene regulation, paving the way for rational drug discovery. Leveraging advanced chemical design, structural biology, next-generation sequencing technologies, and computational approaches, we strive to validate DNA and RNA as precise, druggable therapeutic targets. Our research ultimately seeks to pioneer transcriptome- and genome-targeting strategies, enabling breakthroughs in the treatment of complex diseases such as cancer, infectious diseases, and neurodegenerative disorders.

For more information, please visit our lab website: and .

Selected publications:

Zhang X, Dhir S, Melidis L, Chen Y, Yu Zutao, Simeone A, Spiegel J, Adhikari S, & Balasubramanian S. (2025). Optical control of gene expression using a DNA G-quadruplex targeting reversible photoswitch. Nat. Chem. https://doi.org/10.1038/s41557-025-01792-1