Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery
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Abstract Polysarcosine (pSar) is a polypeptoid based on the endogenous amino acid sarcosine (N-methylated glycine), which has previously shown potent stealth properties. Here, lipid nanoparticles (LNPs) for therapeutic application of messenger RNA were assembled using pSarcosinylated lipids as a tool for particle engineering. Using pSar lipids with different polymeric chain lengths and molar fractions enabled the control of the physicochemical characteristics of the LNPs, such as particle size, morphology, and internal structure. In combination with a suited ionizable lipid, LNPs were assembled, which displayed high RNA transfection potency with an improved safety profile after intravenous injection. Notably, a higher protein secretion with a reduced immunostimulatory response was observed when compared to systems based on polyethylene glycol (PEG) lipids. pSarcosinylated nanocarriers showed a lower proinflammatory cytokine secretion and reduced complement activation compared to PEGylated LNPs. In summary, the described pSar-based LNPs enable safe and potent delivery of mRNA, thus signifying an excellent basis for the development of PEG-free RNA therapeutics.
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Polysarcosine-modified lipids stabilized lipid-based systems against aggregation while reducing the immunostimulatory response.
“Introduction of polysarcosine-modified lipids stabilized lipid-based systems against aggregation while reducing the immunostimulatory response (Nogueira et al., 2020).”
From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Nogueira et al., 2020
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- Authors
- Nogueira, S. S., Schlegel, A., Maxeiner, K., Weber, B., Barz, M., Schroer, M. A., Blanchet, C. E., Svergun, D. I., Ramishetti, S., Peer, D., Langguth, P., Sahin, U., & Haas, H.
- Affiliations
- BioNTech (Germany) (DE)
- Johannes Gutenberg University Mainz (DE)
- Leiden University (NL)
- Deutsches Elektronen-Synchrotron DESY (DE)
- Tel Aviv University (IL)
- BioNTech RNA Pharmaceuticals GmbH , ,
- Corresponding author
- Haas, Heinrich
- ORCID
- Venue
- ACS Applied Nano Materials
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-09-25
- Volume
- 3
- Issue
- 11
- Pages
- 10634-10645
- ISSN
- 2574-0970 (ISSN-L)
- OpenAlex
- W3088467904
- Cited by
- 252
- References
- 55
- Citations by year
- 2026: 47 · 2025: 52 · 2024: 56 · 2023: 47 · 2022: 33 · 2021: 16 · 2020: 1
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- ACS Applied Nano Materials (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (Collaborative Research Center 1066)
- Lewis Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- polysarcosine, polypeptoids, lipid nanoparticles, mRNA delivery, ionizable lipids, stealth nanoparticles, particle engineering, intravenous injection, complement activation, inflammatory cytokines, RNA transfection
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