Engineering genetic medicines and spatial multiomics for immune discovery
My work spans lipid nanoparticles, hydrogel composites, gene editing, immune modulation, and spatial multiomics, connecting translational biomaterials with systems-level studies of tissue immunity.
Research library
Publications.
Up-to-date publication links and citation counts.
Spatial profiling of pooled mRNA-LNP delivery in vivo with NanoSTAMP
- NanoSTAMP combines barcoded pooled LNP screening with spatial-omics readouts to connect formulation identity with cell-type-specific uptake, cargo expression, and neighboring multicellular tissue responses in vivo.
Engineering age-adaptive mRNA lipid nanoparticle cancer vaccines via reprogramming systemic gene expression
- Age-related loss of systemic mRNA expression limits vaccine-induced T cell immunity, while an optimized LNP restores distal antigen expression and therapeutic antitumor efficacy in aged mice.
Lipid nanoparticle composition directs systemic trafficking and tissue-specific T cell immunity after intramuscular injection
- Lipid nanoparticle composition governs their movement from muscle to distant organs, enabling organ-specific antigen expression and driving the formation of tissue-resident cytotoxic T cells.
Crosslinking of lipid nanoparticles enhances the delivery efficiency and efficacy of mRNA vaccines
- A reversible post-assembly crosslinking strategy enhances LNP-mediated mRNA delivery while preserving intracellular release, enabling improved endosomal escape, sustained in vivo expression, and robust immune and antitumor responses.
Engineering Lipid Nanoparticles through Integrated Compositional and Ligand Targeting Enhances β Cell-Directed RNA Delivery
- An integrated strategy combines high-throughput LNP compositional screening with β cell-specific surface ligands to enable selective RNA delivery to pancreatic β cells in mouse and human models.
Imidazolium lipid-based nanoparticles enable effective mRNA delivery and cellular immune response
- Screening 1,944 formulations identified LipidBrickÂŽ LNPs that outperform the clinical benchmark ALC-0315, producing stronger antigen-specific T-cell responses while maintaining low cytotoxicity.
An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy
- An mRNA LNP-incorporated microgel matrix recruits immune cells, supports antigen expression and presentation, and elicits potent antitumor efficacy with a single administration.
A multistep platform identifies spleen-tropic lipid nanoparticles for in vivo T cell-targeted delivery of gene-editing proteins
- A multistep in vivo screening platform identified LNPs that preferentially target the spleen and deliver CRISPR-Cas9 ribonucleoproteins directly to T cells, enabling efficient gene editing without ex vivo manipulation.
Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity
- An LNP screening strategy optimized helper lipid identity and component ratios to enhance dendritic cell delivery of tumour-antigen-encoding mRNA and improve immune activation toward stronger antitumour responses.
Tuning extracellular fluid viscosity to enhance transfection efficiency
- Matching cell culture viscosity to that of biological fluids substantially improves transfection efficiency across multiple gene delivery platforms and cell types.
Optimization of lipid nanoparticles for gene editing of the liver via intraduodenal delivery
- A multi-step screening strategy identified pDNA LNP formulations for intraduodenal delivery and non-viral gene editing in mouse liver, reducing PCSK9 and ANGPTL3 to lower LDL cholesterol.
Multi-step screening of DNA/lipid nanoparticles and co-delivery with siRNA to enhance and prolong gene expression
- A multi-step platform identified optimized plasmid DNA LNPs for liver-targeted delivery and prolonged transgene expression, addressing a major gap in systematic pDNA LNP design.
Size-controlled and shelf-stable DNA particles for production of lentiviral vectors
- Size-controlled pDNA/PEI particles improved lentiviral vector production, with an optimal particle size of 400-500 nm linked to enhanced cellular uptake and transfection efficiency.
Albumin-biomineralized nanoparticles to synergize phototherapy and immunotherapy against melanoma
- Albumin-biomineralized nanoparticles co-delivering a photosensitizer and immunoadjuvant were engineered to couple tumor ablation with immune activation for melanoma therapy.
Y Su, J Choy, X Liu, Y Zhu, J Lin, C Wei, KD Goodier, D Yu, L Cheng, M Patel, X Lu, J Ma, J Wang, HQ Mao*. Stabilizing Anionic mRNA Lipid Nanoparticles by Cleavable Crosslinking of Cholesterol. ACS Applied Materials & Interfaces, 2026.
M Patel, J Choy, L Cheng, E Ariail, M Jain, SR Shannon, D Antov, I Cozzone, X Huang, M Cheng, S Li, J Sun, D Yang, JP Popev, BA Biggs, CJ Erb, BC Chang, T Tian, M Mullaney, G Glenn, Y Zhu, et al., HQ Mao*. Cytokine co-presentation on targeted lipid nanoparticles enhances in vivo T cell engineering. Biomaterials, 2026.
S Schiffersâ , BW Nelsonâ , M Prigge, S Krishna, L Watkins, Y Zhu, N Tyagi, H Beiki, S Das, A Raman, J Ma, T Andresson, HQ Mao, B Wu*, S Oberdoerffer*. N4-Acetylcytidine enhances synthetic mRNA translation yield and fidelity. Nature, 2026.
J Linâ , Y Huâ *, TH Pial, KD Goodier, D Yu, P Brailsford, M Choi-Ali, JT Feng, S Li, Y Zhu, et al., HQ Mao*. Trivalent ions kinetic-gating for producing high-concentration and shelf-stable plasmid DNA/PEI particles. Nature Communications, 2026.
J Choy, L Cheng, M Patel, Y Zhu, J Ma, SS Kang, M Jain, et al., HQ Mao*. Class II peptide-major histocompatibility complex lipid nanoparticles enable in vivo mRNA delivery to antigen-specific CD4+ T cells. ACS Applied Materials & Interfaces, 2026.
J Choy, S Shannon, Y Zhang, SS Kang, Y Zhu, et al., J Schneck*. Nanoscale artificial antigen-presenting cells reveal metabolic interventions modulate clonal composition of CD8+ T cells. Cell Biomaterials, 2026.
B Torkzaban, Y Zhu, C Lopez, JM Alexander, J Ma, Y Sun, KR Maschhoff, et al., J Coller*. Use of poly adenosine tail mimetics to enhance mRNA expression from genes associated with haploinsufficiency disorders. Molecular Therapy Nucleic Acids, 2025.
A Greco, L Cheng, KD Goodier, Y Zhu, J Kong, S Gong, C Erb, J Lin, X Lu, et al., HQ Mao*. Adipocyte-selective mRNA lipid nanoparticles for cell programming with machine learning analysis. Journal of Controlled Release, 2025.
Z Guo, F Wu, C Guo, R Hu, Y Ou, Y Zhu, S Luo, Y Song, P He, C He, Y Xu, et al., X Sun*. Metalloparticle-Engineered Pickering Emulsion Displaying AAV-Vectored Vaccine for Enhancing Antigen Expression and Immunogenicity Against Pathogens. Advanced Materials, 2025.
L Cheng, Y Zhu, J Ma, A Aggarwal, WH Toh, C Shin, et al., HQ Mao*. Machine learning elucidates design features of plasmid deoxyribonucleic acid lipid nanoparticles for cell type-preferential transfection. ACS nano, 2024.
Y Hu, B Eder, J Lin, S Li, Y Zhu, et al., HQ Mao*. Liter-scale manufacturing of shelf-stable plasmid DNA/PEI transfection particles for viral vector production. Molecular Therapy Methods & Clinical Development, 2024.
Y Hu, S Tzeng, L Cheng, J Lin, A Rueda, S Yu, S Li, Z Schneiderman, Y Zhu, et al., HQ Mao*. Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming. Proceedings of the National Academy of Sciences of the United States of America, 2024.
J. Kong, Z.-C. Yao, J. L. Stelzel, Y.-H. Yang, J. Chen, H. Feng, C. Schmidt, C. Zhang, K. Krishnan, L. Chen, J. Pan, K. Ding, Y. Zhu, X. Li, J. C. Doloff, H.-Q. Mao, S. K. Reddy. Granular Nanofiber-Hydrogel Composite-Programmed Regenerative Inflammation and Adipose Tissue Formation. Advanced Healthcare Materials, 2024.
W Chen, Y Song, S Bai, C He, G Zhao, Y Zhu, et al., X Sun*. Cloaking mesoporous polydopamine with bacterial membrane vesicles to amplify local and systemic antitumor immunity. ACS nano, 2023.
W Chen, Y Zhu, J Chen, X Jing, Y Xiong, L Zou, J Li, Q Liu, Y Li, Y Huang, et al., J He*. Potentiating the systemic immunity by bacteria-delivered STING activation in a tumor microenvironment. Advanced Functional Materials, 2023.
Z Guo, Y Zhu, G Du, M Qin, C He, P He, Y Song, W Chen, S Bai, F Wu, et al., X Sun*. Rapid development of a subunit nano-vaccine against drug-resistant Pseudomonas aeruginosa with effective cross-protection. Nano Today, 2022.
J Xue, Y Zhu, S Bai, C He, G Du, Y Zhang, Y Zhong, W Chen, H Wang, et al., X Sun*. Nanoparticles with rough surface improve the therapeutic effect of photothermal immunotherapy against melanoma. Acta Pharmaceutica Sinica B, 2022.
ZC Yao, YH Yang, J Kong, Y Zhu, L Li, C Chang, C Zhang, J Yin, J Chao, et al., HQ Mao*. Biostimulatory micro-fragmented nanofiber-hydrogel composite improves mesenchymal stem cell delivery and soft tissue remodeling. Small, 2022.
S Bai, H Jiang, Y Song, Y Zhu, M Qin, C He, G Du, X Sun*. Aluminum nanoparticles deliver a dual-epitope peptide for enhanced anti-tumor immunotherapy. Journal of Controlled Release, 2022.
S Li, Y Hu, A Li, J Lin, K Hsieh, Z Schneiderman, P Zhang, Y Zhu, et al., HQ Mao*. Payload distribution and capacity of mRNA lipid nanoparticles. Nature Communications, 2022.
X Zhong, G Du, X Wang, Y Ou, H Wang, Y Zhu, X Hao, Z Xie, Y Zhang, et al., X Sun*. Nanovaccines mediated subcutis-to-intestine cascade for improved protection against intestinal infections. Small, 2022.
W Chen, Z Guo, Y Zhu, N Qiao, Z Zhang, X Sun*. Combination of bacterialâphotothermal therapy with an antiâPDâ1 peptide depot for enhanced immunity against advanced cancer. Advanced Functional Materials, 2020.
X Ke, L Shelton, Y Hu, Y Zhu, E Chow, H Tang, JL Santos, HQ Mao*. Surface-functionalized PEGylated nanoparticles deliver messenger RNA to pulmonary immune cells. ACS Applied Materials & Interfaces, 2020.
C Li, X Chen, X Luo, H Wang, Y Zhu, G Du, W Chen, Z Chen, X Hao, et al., X Sun*. Nanoemulsions target to ectopic lymphoids in inflamed joints to restore immune tolerance in rheumatoid arthritis. Nano Letters, 2020.
Review articles 3
W Chen, Y Zhu, J He, X Sun*. Path towards mRNA delivery for cancer immunotherapy from bench to bedside. Theranostics, 2024.
W Chen, Y Zhu, Z Zhang, X Sun*. Advances in Salmonella Typhimurium-based drug delivery system for cancer therapy. Advanced Drug Delivery Reviews, 2022.
S Huang, Y Zhu, L Zhang, Z Zhang*. Recent advances in delivery systems for genetic and other novel vaccines. Advanced Materials, 2022.
Translation
Patents.
Y Zhu, X Liu, H Mao. Compositions and methods of preparing RNA lipid nanoparticles with enhanced stability and transfection efficiency. US Provisional Patent Application; Filed 7/19/2025.
Y Zhu, C Wei, H Mao. Lipid nanoparticles with integrated glycolipid adjuvant to promote tissue-specific cellular immunity. US Provisional Patent Application; Filed 2/18/2025.
Y Zhu, C Wei, D Yu, H Mao. Lipid nanoparticle formulations capable of migrating to systemic organs following intramuscular administration. US Provisional Patent Application; Filed 1/28/2025.
Y Zhu, X Lu, H Mao. Composition screening of lipid nanoparticle for intracellular delivery of gene-editing proteins. PCT/US2025/023531; Filed 4/7/2025.
Y Zhu, C Wei, J Ma, H Mao, et al. A mRNA lipid nanoparticle incorporated nanofiber-hydrogel composite to generate a local immunostimulatory niche for immunotherapy. PCT/US2025/023530; Filed 4/7/2025.
Y Zhu, J Ma, H Mao, et al. Composition of media with defined fluid viscosity for enhancing intracellular delivery of nanoparticles and viral vectors, and methods of use. PCT/US2024/039036; Filed 7/22/2024.
Y Zhu, H Mao, et al. Compositions of Lipid Nanoparticles for Plasmid DNA Delivery to the Liver and Methods for Preparing the Same. PCT/US2023/016938; Filed 3/30/2023.
Y Zhu, Y Hu, H Mao. Methods for preparation of plasmid DNA/lipid particles with defined size for in vitro and in vivo transfection. PCT/US2023, 18/546,221; Filed 8/11/2023.
Y Zhu, Y Hu, H Mao. Composition of shelf-stable plasmid DNA/PEI particles with defined sizes for virus production and method for preparation of the same. PCT/US2023, 18/546,222, Filed 8/11/2023.
Y Zhu, Y Hu, H Mao. Methods for preparation of shelf-stable plasmid DNA/polycation particles with defined sizes for cell transfection. PCT/US2022, 18/261,944; Filed 7/18/2023.
Scientific community
Academic services.
Currently, I am serving as a reviewer for journals across biomaterials, gene delivery, nanomedicine, and translational therapeutics.
Sharing the work
Conference talk moments.
