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227 results on '"Gong, Ningqiang"'

3. High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models

Author

Xue, Lulu, Hamilton, Alex G., Zhao, Gan, Xiao, Zebin, El-Mayta, Rakan, Han, Xuexiang, Gong, Ningqiang, Xiong, Xinhong, Xu, Junchao, Figueroa-Espada, Christian G., Shepherd, Sarah J., Mukalel, Alvin J., Alameh, Mohamad-Gabriel, Cui, Jiaxi, Wang, Karin, Vaughan, Andrew E., Weissman, Drew, and Mitchell, Michael J.

Published
2024
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16. Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy

Author

Metzloff, Ann E., primary, Padilla, Marshall S., additional, Gong, Ningqiang, additional, Billingsley, Margaret M., additional, Han, Xuexiang, additional, Merolle, Maria, additional, Mai, David, additional, Figueroa‐Espada, Christian G., additional, Thatte, Ajay S., additional, Haley, Rebecca M., additional, Mukalel, Alvin J., additional, Hamilton, Alex G., additional, Alameh, Mohamad‐Gabriel, additional, Weissman, Drew, additional, Sheppard, Neil C., additional, June, Carl H., additional, and Mitchell, Michael J., additional

Published
2024
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18. TGF-βR2 signaling coordinates pulmonary vascular repair after viral injury in mice and human tissue

Author

Zhao, Gan, primary, Xue, Lulu, additional, Weiner, Aaron I., additional, Gong, Ningqiang, additional, Adams-Tzivelekidis, Stephanie, additional, Wong, Joanna, additional, Gentile, Maria E., additional, Nottingham, Ana N., additional, Basil, Maria C., additional, Lin, Susan M., additional, Niethamer, Terren K., additional, Diamond, Joshua M., additional, Bermudez, Christian A., additional, Cantu, Edward, additional, Han, Xuexiang, additional, Cao, Yaqi, additional, Alameh, Mohamad-Gabriel, additional, Weissman, Drew, additional, Morrisey, Edward E., additional, Mitchell, Michael J., additional, and Vaughan, Andrew E., additional

Published
2024
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22. In Vivo mRNA CAR T Cell Engineering via Targeted Ionizable Lipid Nanoparticles with Extrahepatic Tropism

Author

Billingsley, Margaret M., primary, Gong, Ningqiang, additional, Mukalel, Alvin J., additional, Thatte, Ajay S., additional, El‐Mayta, Rakan, additional, Patel, Savan K., additional, Metzloff, Ann E., additional, Swingle, Kelsey L., additional, Han, Xuexiang, additional, Xue, Lulu, additional, Hamilton, Alex G., additional, Safford, Hannah C., additional, Alameh, Mohamad‐Gabriel, additional, Papp, Tyler E., additional, Parhiz, Hamideh, additional, Weissman, Drew, additional, and Mitchell, Michael J., additional

Published
2023
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25. Proton-driven transformable nanovaccine for cancer immunotherapy

Author

Gong, Ningqiang, Zhang, Yuxuan, Teng, Xucong, Wang, Yongchao, Huo, Shuaidong, Qing, Guangchao, Ni, Qiankun, Li, Xianlei, Wang, Jinjin, Ye, Xiaoxia, Zhang, Tingbin, Chen, Shizhu, Wang, Yongji, Yu, Jie, Wang, Paul C., Gan, Yaling, Zhang, Jinchao, Mitchell, Michael J., Li, Jinghong, and Liang, Xing-Jie

Published
2020
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31. Lonizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering

Author

Hamilton, Alex G., primary, Swingle, Kelsey L., additional, Joseph, Ryann A., additional, Mai, David, additional, Gong, Ningqiang, additional, Billingsley, Margaret M., additional, Alameh, Mohamad‐Gabriel, additional, Weissman, Drew, additional, Sheppard, Neil C., additional, June, Carl H., additional, and Mitchell, Michael J., additional

Published
2023
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35. In vivo bone marrow microenvironment siRNA delivery using lipid–polymer nanoparticles for multiple myeloma therapy

Author

Guimarães, Pedro P. G., primary, Figueroa-Espada, Christian G., additional, Riley, Rachel S., additional, Gong, Ningqiang, additional, Xue, Lulu, additional, Sewastianik, Tomasz, additional, Dennis, Peter S., additional, Loebel, Claudia, additional, Chung, Amanda, additional, Shepherd, Sarah J., additional, Haley, Rebecca M., additional, Hamilton, Alex G., additional, El-Mayta, Rakan, additional, Wang, Karin, additional, Langer, Robert, additional, Anderson, Daniel G., additional, Carrasco, Ruben D., additional, and Mitchell, Michael J., additional

Published
2023
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41. Combinatorial design of siloxane-incorporated lipid nanoparticles augments intracellular processing for tissue-specific mRNA therapeutic delivery

Author

Xue, Lulu, Zhao, Gan, Gong, Ningqiang, Han, Xuexiang, Shepherd, Sarah J., Xiong, Xinhong, Xiao, Zebin, Palanki, Rohan, Xu, Junchao, Swingle, Kelsey L., Warzecha, Claude C., El-Mayta, Rakan, Chowdhary, Vivek, Yoon, Il-Chul, Xu, Jingcheng, Cui, Jiaxi, Shi, Yi, Alameh, Mohamad-Gabriel, Wang, Karin, Wang, Lili, Pochan, Darrin J., Weissman, Drew, Vaughan, Andrew E., Wilson, James M., and Mitchell, Michael J.

Abstract

Systemic delivery of messenger RNA (mRNA) for tissue-specific targeting using lipid nanoparticles (LNPs) holds great therapeutic potential. Nevertheless, how the structural characteristics of ionizable lipids (lipidoids) impact their capability to target cells and organs remains unclear. Here we engineered a class of siloxane-based ionizable lipids with varying structures and formulated siloxane-incorporated LNPs (SiLNPs) to control in vivo mRNA delivery to the liver, lung and spleen in mice. The siloxane moieties enhance cellular internalization of mRNA-LNPs and improve their endosomal escape capacity, augmenting their mRNA delivery efficacy. Using organ-specific SiLNPs to deliver gene editing machinery, we achieve robust gene knockout in the liver of wild-type mice and in the lungs of both transgenic GFP and Lewis lung carcinoma (LLC) tumour-bearing mice. Moreover, we showed effective recovery from viral infection-induced lung damage by delivering angiogenic factors with lung-targeted Si5-N14 LNPs. We envision that our SiLNPs will aid in the clinical translation of mRNA therapeutics for next-generation tissue-specific protein replacement therapies, regenerative medicine and gene editing.

Published
2024
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42. Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo

Author

Han, Xuexiang, Alameh, Mohamad-Gabriel, Gong, Ningqiang, Xue, Lulu, Ghattas, Majed, Bojja, Goutham, Xu, Junchao, Zhao, Gan, Warzecha, Claude C., Padilla, Marshall S., El-Mayta, Rakan, Dwivedi, Garima, Xu, Ying, Vaughan, Andrew E., Wilson, James M., Weissman, Drew, and Mitchell, Michael J.

Abstract

Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine–thiol–acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure–activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine–ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.

Published
2024
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46. Rational Design of Bisphosphonate Lipid-like Materials for mRNA Delivery to the Bone Microenvironment

Author

Xue, Lulu, primary, Gong, Ningqiang, additional, Shepherd, Sarah J., additional, Xiong, Xinhong, additional, Liao, Xueyang, additional, Han, Xuexiang, additional, Zhao, Gan, additional, Song, Chao, additional, Huang, Xisha, additional, Zhang, Hanwen, additional, Padilla, Marshall S., additional, Qin, Jingya, additional, Shi, Yi, additional, Alameh, Mohamad-Gabriel, additional, Pochan, Darrin J., additional, Wang, Karin, additional, Long, Fanxin, additional, Weissman, Drew, additional, and Mitchell, Michael J., additional

Published
2022
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47. Physical & Chemical Microwave Ablation (MWA) Enabled by Nonionic MWA Nanosensitizers Repress Incomplete MWA-Arised Liver Tumor Recurrence

Author

Hou, Qidi, primary, Zhang, Kun, additional, Chen, Sitong, additional, Chen, Jie, additional, Zhang, Yan, additional, Gong, Ningqiang, additional, Guo, Weisheng, additional, Fang, Chao, additional, Wang, Luo, additional, Jiang, Jian, additional, Dou, Jianping, additional, Liang, Xingjie, additional, Yu, Jie, additional, and Liang, Ping, additional

Published
2022
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48. Lipid Nanoparticle Delivery of Small Proteins for Potent In VivoRAS Inhibition

Author

Haley, Rebecca M., Chan, Alexander, Billingsley, Margaret M., Gong, Ningqiang, Padilla, Marshall S., Kim, Emily H., Wang, Hejia, Yin, Dingzi, Wangensteen, Kirk J., Tsourkas, Andrew, and Mitchell, Michael J.

Abstract

Mutated RAS proteins are potent oncogenic drivers and have long been considered “undruggable”. While RAS-targeting therapies have recently shown promise, there remains a clinical need for RAS inhibitors with more diverse targets. Small proteins represent a potential new therapeutic option, including K27, a designed ankyrin repeat protein (DARPin) engineered to inhibit RAS. However, K27 functions intracellularly and is incapable of entering the cytosol on its own, currently limiting its utility. To overcome this barrier, we have engineered a lipid nanoparticle (LNP) platform for potent delivery of functional K27-D30─a charge-modified version of the protein─intracellularly in vitroand in vivo. This system efficiently encapsulates charge-modified proteins, facilitates delivery in up to 90% of cells in vitro, and maintains potency after at least 45 days of storage. In vivo, these LNPs deliver K27-D30 to the cytosol of cancerous cells in the liver, inhibiting RAS-driven growth and ultimately reducing tumor load in an HTVI-induced mouse model of hepatocellular carcinoma. This work shows that K27 holds promise as a new cancer therapeutic when delivered using this LNP platform. Furthermore, this technology has the potential to broaden the use of LNPs to include new cargo types─beyond RNA─for diverse therapeutic applications.

Published
2023
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