DataVXACS Applied Nano MaterialsPaper
journal article·2020-11-25Open access

Polysarcosine-Functionalized Lipid Nanoparticles for Therapeutic mRNA Delivery

Sara S. Nogueira, Anne Schlegel, Konrad Maxeiner, Benjamin Weber, Matthias Barz, Martin A. Schroer, Clement E. Blanchet, Dmitri I. Svergun, Srinivas Ramishetti, Dan Peer, Peter Langguth, Ugur Sahin, Heinrich Haas

ACS Applied Nano Materials· Volume 3· Issue 11
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Source abstract

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.
Source: openalex_inverted_index · Quality: baseline

Research context

PolymersNanomaterials

OpenAlex topics: RNA Interference and Gene Delivery · Advanced biosensing and bioanalysis techniques · Nanopore and Nanochannel Transport Studies

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

BioNTech RNA Pharmaceuticals GmbH, 55131 Mainz, Germany

Institute of Organic Chemistry, Johannes Gutenberg University Mainz, 55128 Mainz, Germany

Leiden Academic Center for Drug Research, Leiden University, 2333 CC Leiden, Netherlands

European Molecular Biology Laboratory (EMBL) Hamburg c/o DESY, 22607 Hamburg, Germany

Laboratory of Precision NanoMedicine, The Shmunis School of Biomedicine and Cancer Research and Dept. of Materials Sciences and Engineering, Tel Aviv University, Tel Aviv 69978, Israel

Department of Pharmaceutics and Biopharmaceutics, Johannes Gutenberg University Mainz, 55099 Mainz, Germany

TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz gGmbH, 55099 Mainz, Germany

Research Center for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University Mainz, 55099 Mainz, Germany

Funding

Deutsche Forschungsgemeinschaft · Lewis Trust

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