Efficient mRNA delivery using lipid nanoparticles modified with fusogenic coiled-coil peptides

Zeng, Ye; Shen, Mengjie; Pattipeiluhu, Roy; Zhou, Xuequan; Zhang, Yun; Bakkum, Thomas; Sharp, Thomas H.; Boyle, Aimee L.; Kros, Alexander

doi:10.1039/d3nr02175k

Cited by 6 publications

(5 citation statements)

References 74 publications

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“…Finally, a cytotoxicity assay revealed no significant differences in the cytotoxicity between CPE4- and unfunctionalized LNPs. Altogether, these results showed that poor endosomal escape can be avoided by LNP internalization through CPE4/CPK4-induced membrane fusion, resulting in high transfection efficiency and enhanced mRNA expression in vitro …”

Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 76%

“…The lipopeptide-based fusion system CPE/CPK has already been used in many applications, such as cell sorting, liposome fusion, ,, liposome cell fusion, ,, lipid nanoparticle cell fusion, cell–cell fusion, and anion transporter delivery to membranes …”

Section: Fusogenic Peptidesmentioning

confidence: 99%

“… Schematic representation of the nonviral lipid nanoparticles (LNPs) that induce efficient mRNA delivery within cells when modified with fusogenic coiled-coil peptides. Reproduced from ref ( 32 ) with permission from the Royal Society of Chemistry. …”

Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 99%

“…Altogether, these results showed that poor endosomal escape can be avoided by LNP internalization through CPE4/CPK4-induced membrane fusion, resulting in high transfection efficiency and enhanced mRNA expression in vitro . 32 …”

Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 99%

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Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Aschmann,

Knol,

Kros

2024

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: For the delivery of drugs, different nanosized drug carriers (e.g., liposomes, lipid nanoparticles, and micelles) have been developed in order to treat diseases that afflict society. Frequently, these vehicles are formed by the self-assembly of small molecules to encapsulate the therapeutic cargo of interest. Over decades, nanoparticles have been optimized to make them more efficient and specific to fulfill tailor-made tasks, such as specific cell targeting or enhanced cellular uptake. In recent years, lipid-based nanoparticles in particular have taken center stage; however, off-targeting side effects and poor endosomal escape remain major challenges since therapies require high efficacy and acceptable toxicity.To overcome these issues, many different approaches have been explored to make drug delivery more specific, resulting in reduced side effects, to achieve an optimal therapeutic effect and a lower required dose. The fate of nanoparticles is largely dependent on size, shape, and surface charge. A common approach to designing drug carriers with targeting capability is surface modification. Different approaches to functionalize nanoparticles have been investigated since the attachment of targeting moieties plays a significant role in whether they can later interact with surface-exposed receptors of cells. To this end, various strategies have been used involving different classes of biomolecules, such as small molecules, nucleic acids, antibodies, aptamers, and peptides. Peptides in particular are often used since there are many receptors overexpressed in different specific cell types. Furthermore, peptides can be produced and modified at a low cost, enabling high therapeutic screening. Cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs) are frequently used for this purpose. Less studied in this context are fusogenic coiled-coil peptides.Lipid-based nanoparticles functionalized with these peptides are able to avoid the endolysosomal pathway; instead such particles can be taken up by membrane fusion, resulting in increased delivery of payload. Furthermore, they can be used for targeting cells/organs but are not directed at surface-exposed receptors. Instead, they recognize complementary peptide sequences, facilitating their uptake into cells.In this Account, we will discuss peptides as moieties for enhanced cytosolic delivery, targeted uptake, and how they can be attached to lipid-based nanoparticles to alter their properties. We will discuss the properties imparted to the particles by peptides, surface modification approaches, and recent examples showing the power of peptides for in vitro and in vivo drug delivery. The main focus will be on the functionalization of lipid-based nanoparticles by fusogenic coiled-coil peptides, highlighting the relevance of this concept for the development of future therapeutics.

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Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 76%

Section: Fusogenic Peptidesmentioning

confidence: 99%

Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 99%

Section: Lipid-based Nanoparticles Functionalized With Fusogenic Pept...mentioning

confidence: 99%

See 2 more Smart Citations

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Aschmann,

Knol,

Kros

2024

Acc. Chem. Res.

Self Cite

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“…There are several biomaterial designs and modifications that show promise for the safe delivery of mRNA, including lipids, lipid-like materials, polymers, and inorganic nanoparticles . Currently, lipid nanoparticles (LNPs) are the state-of-the-art vector for packaging, protecting, and releasing mRNA molecules within cells, as evidenced by the success of two COVID-19 mRNA-LNP vaccine formulations that received FDA approval in 2020. − LNPs are typically composed of four lipid componentsan ionizable lipid, cholesterol, a helper lipid, and a poly(ethylene glycol)-lipid conjugate, which can be varied to produce distinct formulations with desired physicochemical properties. − However, the efficacy of LNPs in transfecting cells is limited by their ability to induce endo/lysosomal escape since they enter cells through endocytosis and are subjected to endolysosomal trafficking . Typically, less than 5% of the intracellularly delivered dose of mRNA by LNPs is able to reach the cytoplasm .…”

Section: Introductionmentioning

confidence: 99%

Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Zeng,

Estapé Senti,

Labonia

et al. 2023

ACS Nano

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Strategies for Organ‐Targeted mRNA Delivery by Lipid Nanoparticles

Liao,

Zeng

et al. 2024

WIREs Nanomed Nanobiotechnol

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Messenger RNA (mRNA) technology has rapidly evolved, significantly impacting various therapeutic applications, including vaccines, protein replacement, and gene editing. Lipid nanoparticles (LNPs) have emerged as a pivotal nonviral vector for mRNA delivery, crucial for organ‐targeted therapies. Despite their success, most LNP formulations predominantly target the liver, limiting their use in nonliver diseases. This review explores strategies to achieve organ‐specific mRNA delivery using LNPs, including the discovery of new lipid structures, modification of targeting ligands, incorporation of additional components, and optimization of LNP formulations. These advancements aim to enhance the precision and efficacy of mRNA therapeutics across a broader range of diseases.

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Efficient mRNA delivery using lipid nanoparticles modified with fusogenic coiled-coil peptides

Abstract: Gene delivery has great potential in modulating protein expression in specific cells to treat diseases. Such therapeutic gene delivery demands sufficient cellular internalization and endosomal escape. Of the various nonviral...

Cited by 6 publications

References 74 publications

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

Fusogenic Coiled-Coil Peptides Enhance Lipid Nanoparticle-Mediated mRNA Delivery upon Intramyocardial Administration

Strategies for Organ‐Targeted mRNA Delivery by Lipid Nanoparticles

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