Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-Loaded Lipid Nanoparticles

Masaki Gomi; Yu Sakurai; Minami Sato; Hiroki Tanaka; Yumi Miyatake; Koichi Fujiwara; Mizuki Watanabe; Satoshi Shuto; Yuta Nakai; Kota Tange; Hiroto Hatakeyama; Hidetaka Akita

doi:10.1002/adhm.202202528

Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-Loaded Lipid Nanoparticles

Masaki Gomi, Yu Sakurai, Minami Sato, Hiroki Tanaka, Yumi Miyatake, Koichi Fujiwara, Mizuki Watanabe, Satoshi Shuto, Yuta Nakai, Kota Tange, Hiroto Hatakeyama, Hidetaka Akita

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

Abstract

Lipid nanoparticles (LNPs) are one of the most successful technologies in messenger RNA (mRNA) delivery. While the liver is the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, it is reported on the development of an LNP that targets secondary lymphoid tissues. New types of alcohol-soluble phosphatidylserine (PS) derivatives are designed as materials that target immune cells and then incorporated into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP is extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study will be a promising strategy for clinical applications that involve delivering mRNA to the spleen.

Original language	English
Journal	Advanced Healthcare Materials
DOIs	https://doi.org/10.1002/adhm.202202528
Publication status	Accepted/In press - 2022

Keywords

lipid nanoparticles
lymph nodes
mRNA delivery
phosphatidylserine
spleen

ASJC Scopus subject areas

Biomaterials
Biomedical Engineering
Pharmaceutical Science

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10.1002/adhm.202202528

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title = "Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-Loaded Lipid Nanoparticles",

abstract = "Lipid nanoparticles (LNPs) are one of the most successful technologies in messenger RNA (mRNA) delivery. While the liver is the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, it is reported on the development of an LNP that targets secondary lymphoid tissues. New types of alcohol-soluble phosphatidylserine (PS) derivatives are designed as materials that target immune cells and then incorporated into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP is extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study will be a promising strategy for clinical applications that involve delivering mRNA to the spleen.",

keywords = "lipid nanoparticles, lymph nodes, mRNA delivery, phosphatidylserine, spleen",

author = "Masaki Gomi and Yu Sakurai and Minami Sato and Hiroki Tanaka and Yumi Miyatake and Koichi Fujiwara and Mizuki Watanabe and Satoshi Shuto and Yuta Nakai and Kota Tange and Hiroto Hatakeyama and Hidetaka Akita",

note = "Funding Information: M.G., Y.S., and M.S. contributed equally to this work. This work was supported by the JST CREST grant (grant number JPMJCR17H1), JSPS KAKENHI (grant numbers 20H00657, 21J20728, 21K18320), and The Canon Foundation. This work was partly supported by Global Facility Center (GFC), Hokkaido University. M.G. was supported by a Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (grant number N‐201405). The authors also thank Dr. Milton S. Feather for helpful advice on the use of English in this manuscript. Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",

year = "2022",

doi = "10.1002/adhm.202202528",

language = "English",

journal = "Advanced healthcare materials",

issn = "2192-2640",

publisher = "John Wiley and Sons Ltd",

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TY - JOUR

T1 - Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-Loaded Lipid Nanoparticles

AU - Gomi, Masaki

AU - Sakurai, Yu

AU - Sato, Minami

AU - Tanaka, Hiroki

AU - Miyatake, Yumi

AU - Fujiwara, Koichi

AU - Watanabe, Mizuki

AU - Shuto, Satoshi

AU - Nakai, Yuta

AU - Tange, Kota

AU - Hatakeyama, Hiroto

AU - Akita, Hidetaka

N1 - Funding Information: M.G., Y.S., and M.S. contributed equally to this work. This work was supported by the JST CREST grant (grant number JPMJCR17H1), JSPS KAKENHI (grant numbers 20H00657, 21J20728, 21K18320), and The Canon Foundation. This work was partly supported by Global Facility Center (GFC), Hokkaido University. M.G. was supported by a Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan (grant number N‐201405). The authors also thank Dr. Milton S. Feather for helpful advice on the use of English in this manuscript. Publisher Copyright: © 2022 Wiley-VCH GmbH.

PY - 2022

Y1 - 2022

N2 - Lipid nanoparticles (LNPs) are one of the most successful technologies in messenger RNA (mRNA) delivery. While the liver is the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, it is reported on the development of an LNP that targets secondary lymphoid tissues. New types of alcohol-soluble phosphatidylserine (PS) derivatives are designed as materials that target immune cells and then incorporated into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP is extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study will be a promising strategy for clinical applications that involve delivering mRNA to the spleen.

AB - Lipid nanoparticles (LNPs) are one of the most successful technologies in messenger RNA (mRNA) delivery. While the liver is the most frequent target for LNP delivery of mRNA, technologies for delivering mRNA molecules to extrahepatic tissues are also important. Herein, it is reported on the development of an LNP that targets secondary lymphoid tissues. New types of alcohol-soluble phosphatidylserine (PS) derivatives are designed as materials that target immune cells and then incorporated into LNPs using a microfluidic technique with a high degree of scalability and reproducibility. The resulting LNP that contained the synthesized PS delivered mRNA to the spleen much more efficiently compared to a control LNP. A sub-organ analysis revealed that the PS-loaded LNP is extensively taken up by tissue-resident macrophages in the red pulp and the marginal zone of the spleen. Thus, the PS-loaded LNP reported in this study will be a promising strategy for clinical applications that involve delivering mRNA to the spleen.

KW - lipid nanoparticles

KW - lymph nodes

KW - mRNA delivery

KW - phosphatidylserine

KW - spleen

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DO - 10.1002/adhm.202202528

M3 - Article

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AN - SCOPUS:85145158233

SN - 2192-2640

JO - Advanced healthcare materials

JF - Advanced healthcare materials

ER -

Delivering mRNA to Secondary Lymphoid Tissues by Phosphatidylserine-Loaded Lipid Nanoparticles

Abstract

Keywords

ASJC Scopus subject areas

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