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Biomedical Engineering Research Seminar

Zongjie (Daniel) Wang, Ph.D.

Biohub Chicago

Abstract

Lipid nanoparticles (LNPs) have enabled a new generation of in vivo mRNA therapeutics, yet delivery and functional expression remain suboptimal in many tissues even after extensive lipid optimization. Here, we show that this gap is strongly shaped by cellular metabolism: the physiologic metabolome imposes constraints that suppress LNP uptake and downstream expression. Guided by multi-omics profiling, we identify downregulated amino acid–related pathways as a major limiting axis and develop an amino acid supplement (AAS) that restores these metabolic programs. In this talk, Dr. Wang will present evidence that metabolic state is a dominant, and tunable, determinant of LNP performance. Co-administration of AAS markedly increases mRNA expression across multiple cell types and lipid formulations, achieving ~5–20-fold gains in vitro. In vivo, AAS enhances reporter expression across administration routes and improves therapeutic outcomes in an acetaminophen-induced liver injury model. Finally, I will describe how AAS potentiates lung-targeted LNP gene editing, increasing editing from ~20–30% to ~85–90% in a single dose. Collectively, these findings advance a framework in which nanoparticle efficacy reflects not only vector chemistry but also the metabolic microenvironment of target cells. By engineering this microenvironment, we introduce an orthogonal and broadly applicable lever for improving RNA delivery and genome editing in vivo.

Bio

Zongjie (Daniel) Wang is a Group Leader and Principal Investigator at Biohub Chicago (formerly Chan Zuckerberg Biohub Chicago). His lab develops microsystems and multi-omics approaches for high-throughput screening and therapeutic translation at the intersection of immunotherapy and precision medicine. He earned his Ph.D. in Biomedical Engineering from the University of Toronto and trained as a postdoctoral scholar at Northwestern University. Daniel has published widely across microtechnologies and nanomedicine, including Science Translational Medicine (2026), Nature Reviews Drug Discovery (2026), Nature Biomedical Engineering (2025, 2024, 2023, 2022), and Nature Chemistry (2023), with more than 6,000 citations to date. His honors include Crain’s Chicago Business “40 Under 40” (2024), the President’s Award for Excellence (ISAC, 2025), the Young Alumni Achievement Award (UBC, 2025), and the Dimitris N. Chorafas Foundation Prize (Weizmann Institute, 2023). He is a co-founder of CTRL Therapeutics.