This paper identifies age-related impairment in systemic mRNA translation as a barrier to mRNA vaccine efficacy and develops an LNP formulation to restore transgene expression and T cell immunity in aged hosts.

bioRxiv · Apr 12, 2026 · PreprintBioengineering

Crosslinking of Lipid Nanoparticles Enhances the Delivery Efficiency and Efficacy of mRNA Vaccines

Xiang Liu, Yining Zhu, Christine Y. Wei, Jinghan Lin, Di Yu, Jiayuan Kong, Fangchi Shao, Jingyao Ma, T. Xu, Xiaoya Lu, Yunhe Su, Kailei D. Goodier, Leonardo Cheng, Wu Han Toh, Christopher J. Erb, , Hai‐Quan Mao

This paper introduces a crosslinking method to improve mRNA LNP stability and delivery efficiency, showing enhanced structural integrity and transfection performance in vitro and in vivo.

Nature Chemical Engineering · Feb 16, 2026Peer-reviewedBioengineering

Controlling Payload Heterogeneity in Lipid Nanoparticles for RNA-Based Therapeutics

Turash Haque Pial, Sixuan Li, Jinghan Lin, Tza-Huei Wang, Hai‐Quan Mao, Tine Curk

This study identifies the causes of payload heterogeneity in lipid nanoparticles and proposes methods to improve RNA distribution uniformity.

Advanced Functional Materials · Jan 16, 2026Peer-reviewedBioengineering

Buffer Valency Engineering Enables High-concentration and Shelf-stable DNA Transfection Particles for Viral Vector Production

Jinghan Lin, Yizong Hu, Turash Haque Pial, Kailei D. Goodier, Di Yu, Marine Guise, Paetra Brailsford, Maria Choi-Ali, Sixuan Li, Yining Zhu, Jingyao Ma, Leonardo Cheng, Xiaoya Lu, Nicole Korinetz, Jeff Wang, , Hai‐Quan Mao

This paper develops a method to create high-concentration, shelf-stable DNA transfection particles for AAV production, achieving tenfold higher pDNA concentration and reduced dosing volume.

bioRxiv · Jul 2, 2025 · PreprintBiochemistry

Systemic trafficking of mRNA lipid nanoparticle vaccine following intramuscular injection generates potent tissue-specific T cell response

Christine Y. Wei, Yining Zhu, Xiaoya Lu, Kailei D. Goodier, Di Yu, Xiang Liu, Joseph Choy, Alejandro Téllez Calderón, Jingyao Ma, Yunhe Su, Jinghan Lin, S.-H. Li, Jonathan P. Schneck, Sean C. Murphy, Hai‐Quan Mao

This study shows that mRNA lipid nanoparticles (LNPs) can be tailored to traffic to specific organs, enhancing tissue-specific T cell responses and vaccine efficacy.

bioRxiv · Apr 21, 2025 · PreprintBioengineering

mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy

Yining Zhu, Zhi‐Cheng Yao, S.-H. Li, Jingyao Ma, Christine Y. Wei, Di Yu, Jessica L. Stelzel, Bobby Y.X. Ni, Yang Miao, Kyra Van Batavia, Xiaoya Lu, Jinghan Lin, Yifan Dai, Jiayuan Kong, Ruochen Shen, , Hai‐Quan Mao

The paper develops a nanofiber-hydrogel composite incorporating mRNA lipid nanoparticles to create a local immunostimulatory niche for cancer immunotherapy, showing enhanced immune responses with a single dose.

bioRxiv · Jan 27, 2025 · PreprintBioengineering