Engineering the Future of Medicine.

Authors
Zhu Y*, Miao Y*, Anderson IJ, Li Y, Aghnatios B, No J, Ma J, Yu D, Wei C, Lu X, Wang J, van de Klashorst J, Mao HQ, Hickey JW#.

• 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.

Authors
Zhu Y*, Wei C*, Ma J, Yu D, Wang J, Lu X, Goodier KD, Lin J, Liu X, Su Y, Jiang Z, Greco AH, Cheng L, Toh WH, Miao Y, Schneck JP, Doloff JC, Hickey JW, Mao HQ.

• 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.

Authors
Wei C*, Zhu Y*#, Lu X, Goodier KD, Yu D, Liu X, Choy J, Téllez Calderón A, Su Y, Ma J, Lin J, Li S, Schneck JP, Murphy SC#, Mao HQ#.

• 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.

Authors
Liu X*, Zhu Y*, Wei C, Lin J, Yu D, Kong J, Shao F, Ma J, Xu T, Lu X, Su Y, Goodier KD, Cheng L, Toh WH, Erb CJ, Li S, Wang TH, Mao HQ#.

• 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.

Authors
Yu D*, Zhu Y*, Roca-Rivada A, Guo Z, Cheng L, Weng G, Toh WH, Martin-Vazquez E, Buemi A, Mourad NI, Kasinathan D, Ma J, Lin J, Kong J, Quiroz VM, Tzeng SY, Lu X, Su Y, Liu X, Shen Z, Goodier KD, Wei C, Greco AH, Doloff JC, Eizirik DL#, Mao HQ#.

• 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.

Authors
Lin J*, Zhu Y*, Cheng L, Wei C, Kong J, Choy J, Lu X, Yu D, Ma J, Liu X, Su Y, Naganand S, Gueguen C, Huaulme Q, Urguia P, Mao HQ#.

• Screening 1,944 formulations identified LipidBrick® LNPs that outperform the clinical benchmark ALC-0315, producing stronger antigen-specific T-cell responses while maintaining low cytotoxicity.

Authors
Zhu Y*, Yao ZC*, Li S*, Ma J, Wei C, Yu D, Stelzel JL, Ni BYX, Miao Y, Van Batavia K, Lu X, Lin J, Dai Y, Kong J, Shen R, Goodier KD, Liu X, Cheng L, Vuong I, Howard GP, Livingston NK, Choy J, Schneck JP, Doloff JC, Reddy SK, Hickey JW, Mao HQ#.

• An mRNA LNP-incorporated microgel matrix recruits immune cells, supports antigen expression and presentation, and elicits potent antitumor efficacy with a single administration.

Authors
Lu X*, Zhu Y*, Wei C, Cheng L, Goodier KD, Kong J, Gao X, Yu D, Liu X, Long Y, Lin J, Ma J, Su Y, Mao HQ#.

• 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.

Authors
Zhu Y, Ma J, Shen R, Lin J, Li S, Lu X, Stelzel JL, Kong J, Cheng L, Vuong I, Yao ZC, Wei C, Korinetz NM, Toh WH, Choy J, Reynolds RA, Shears MJ, Cho WJ, Livingston NK, Howard GP, Hu Y, Tzeng SY, Zack DJ, Green JJ, Zheng L, Doloff JC, Schneck JP, Reddy SK, Murphy SC#, Mao HQ#.

• 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.

Authors
Ma J*, Zhu Y*, Kong J, Yu D, Toh WH, Jain M, Ni Q, Ge Z, Lin J, Choy J, Cheng L, Konstantopoulos K, Konig M, Sun S#, Mao HQ#.

• Matching cell culture viscosity to that of biological fluids substantially improves transfection efficiency across multiple gene delivery platforms and cell types.

Authors
Zhu Y*, Cai SS*, Ma J, Cheng L, Wei C, Aggarwal A, Toh WH, Shin C, Shen R, Kong J, Mao SA, Lao YH, Leong KW#, Mao HQ#.

• 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.

Authors
Zhu Y, Shen R, Vuong I, Reynolds RA, Shears MJ, Yao ZC, Hu Y, Cho WJ, Kong J, Reddy SK, Murphy SC#, Mao HQ#.

• 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.

Authors
Hu Y*, Zhu Y*, Sutherland ND, Wilson DR, Pang M, Liu E, Staub JR, Berlinicke CA, Zack DJ, Green JJ, Reddy SK, Mao HQ#.

• 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.

Authors
Zhu Y*, Xue J, Chen W, Bai S, Zheng T, He C, Guo Z, Jiang M, Du G, Sun X#.

• Albumin-biomineralized nanoparticles co-delivering a photosensitizer and immunoadjuvant were engineered to couple tumor ablation with immune activation for melanoma therapy.