Asst Prof HOU Xucheng

Biomacromolecules such as antibodies and RNA therapeutics hold tremendous promise to transform the treatment of human disease. However, their clinical translation is often constrained by complex biological barriers, including inefficient delivery to target tissues and cells, and restricted intracellular trafficking. These challenges diminish therapeutic efficacy and can lead to off-target effects. At the Hou Lab, we integrate chemistry, biomaterials science, and molecular bioengineering to understand and overcome these biological barriers. By coupling mechanistic insights with rational design, we aim to translate fundamental discoveries into enabling technologies that enhance precision and efficiency. Our goal is to develop next-generation biomacromolecular therapeutics for genetic disorders, infections, cancer, and central nervous system disorders.

Development of next-generation lipid nanoparticles (LNPs) for the efficient and targeted delivery of RNA therapeutics, including mRNA, circular RNA (circRNA), and self-amplifying RNA (saRNA).

Rational engineering of RNA molecules, leveraging expanded structural and topological designs to improve translation efficiency, tissue selectivity, stability, and programmable control of gene expression.

Discovery of novel small-molecule ligands to enable targeted delivery of siRNAs and antisense oligonucleotides.

Chemical synthesis and modification of siRNAs and oligonucleotides to enhance gene-silencing potency, specificity, and durability.

1. Xue, Y.#, Hou, X.#*, Wang, S., Zhang, Y., Zhong, Y., Kang, D. D., Wang C., Li, H., Yu, C., Liu, Z., Tian, M., Cao, D., Zheng Y.Y., Deng, B., Hamon, P., Merad, M., Dong. Y.* Antimicrobial peptide delivery to lung as peptibody mRNA in antinflammatory lipids treats multidrug-resistant bacterial pneumonia. Nature Biotechnology (2025). DOI: 10.1038/s41587-025-02928-x
2. Xue, Y.#, Hou, X.#*, Zhong, Y.#, Zhang. Y., Du, S., Kang, D. D., Wang, L., Wang, C., L, H., Wang, S., Liu, Z., Tian, M., Guo, K., Cao, D., Deng, B., McComb, D. W., Purisic, E., Dai,J., Hamon, P., Brown, B. D., Tsankova, N., M, Merad, M., Irvine, D. J., Weiss, R., Dong, Y*. LNP-RNA-mediated antigen presentation leverages SARS-CoV-2-specific immunity for cancer treatment. Nature Communications (2025). DOI: 10.1038/s41467-025-57149-2
3. Cao, D.#, Hou, X.#, Wang, C.#, Wang, S.#, Liu, Z., Tian, M., Guo, K., Li, H., Kang, D. D., Zhong, Y., Xue, Y., Yu. C., Deng, B., Dong, Y.* Lipid nanoparticles for mRNA delivery in brain via systemic administration. Science Advances (2025). DOI: 10.1126/sciadv.adw0730
4. Zhang, Y.#, Hou, X.#, Du, S., Xue, Y., Yan, J., Kang, D., Zhong, Y., Wang, C., Deng, B., McComb, D., Dong, Y.* Close the cancer-immunity cycle by integrating lipid nanoparticle-mRNA formulations and dendritic cell therapy. Nature Nanotechnology (2023). DOI: 10.1038/s41565-023-01453-9
5. Hou, X., Zaks, T.*, Langer, R.*, Dong, Y.* Lipid nanopartices for mRNA delivery. Nature Reviews Materials (2021). DOI: 10.1038/s41578-021-00358-0
6. Hou, X.#, Zhang. X.#, Zhao, W., Zeng, C., Deng B., McComb, D. W., Du, S., Zhang, C., Li, W., Dong. Y.* Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nature Nanotechnology (2020). DOI: 10.1038/s41565-019-0600-1