Engineering LNPs with polysarcosine lipids for mRNA delivery

Diana D. Kang; Xucheng Hou; Leiming Wang; Yonger Xue; Haoyuan Li; Yichen Zhong; Siyu Wang; Binbin Deng; David W. McComb; Yizhou Dong

Bioactive Materials (Jul 2024)

Engineering LNPs with polysarcosine lipids for mRNA delivery

Diana D. Kang,
Xucheng Hou,
Leiming Wang,
Yonger Xue,
Haoyuan Li,
Yichen Zhong,
Siyu Wang,
Binbin Deng,
David W. McComb,
Yizhou Dong

Affiliations

Diana D. Kang: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA
Xucheng Hou: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Corresponding author.
Leiming Wang: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Yonger Xue: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA
Haoyuan Li: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Yichen Zhong: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Siyu Wang: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
Binbin Deng: Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA
David W. McComb: Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, 43212, USA; Department of Materials Science and Engineering, The Ohio State University, Columbus, OH, 43210, USA
Yizhou Dong: Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA; Corresponding author. Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

Journal volume & issue: Vol. 37
pp. 86 – 93

Abstract

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Since the approval of the lipid nanoparticles (LNP)-mRNA vaccines against the SARS-CoV-2 virus, there has been an increased interest in the delivery of mRNA through LNPs. However, current LNP formulations contain PEG lipids, which can stimulate the generation of anti-PEG antibodies. The presence of these antibodies can potentially cause adverse reactions and reduce therapeutic efficacy after administration. Given the widespread deployment of the COVID-19 vaccines, the increased exposure to PEG may necessitate the evaluation of alternative LNP formulations without PEG components. In this study, we investigated a series of polysarcosine (pSar) lipids as alternatives to the PEG lipids to determine whether pSar lipids could still provide the functionality of the PEG lipids in the ALC-0315 and SM-102 LNP systems. We found that complete replacement of the PEG lipid with a pSar lipid can increase or maintain mRNA delivery efficiency and exhibit similar safety profiles in vivo.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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