In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA

Medjmedj, Ayoub; Ngalle-Loth, Albert; Clemençon, Rudy; Hamacek, Josef; Pichon, Chantal; Perche, Federico

doi:10.3390/nano12142446

Cited by 9 publications

(4 citation statements)

References 64 publications

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“…While there are a handful of methods to characterize encapsulation efficiency of an LNP formulation for its cargo, modified RiboGreen assay is by far the most common [25][26][27][28][29][30] . RiboGreen is a dye developed for quantitation of RNA in which fluorescence is produced upon nucleic acid binding 31 .…”

Section: Encapsulation Efficiency Based On Input Rna Concentrationmentioning

confidence: 99%

A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient

Schober,

Story,

Arya

2024

Sci Rep

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With the recent success of lipid nanoparticle (LNP) based SARS-CoV-2 mRNA vaccines, the potential for RNA therapeutics has gained widespread attention. LNPs are promising non-viral delivery vectors to protect and deliver delicate RNA therapeutics, which are ineffective and susceptible to degradation alone. While food and drug administration (FDA) approved formulations have shown significant promise, benchmark lipid formulations still require optimization and improvement. In addition, the translatability of these formulations for several different RNA cargo sizes has not been compared under the same conditions. Herein we analyze “gold standard” lipid formulations for encapsulation efficiency of various non-specific RNA cargo lengths representing antisense oligonucleotides (ASO), small interfering RNA (siRNA), RNA aptamers, and messenger RNA (mRNA), with lengths of 10 bases, 21 base pairs, 96 bases, 996 bases, and 1929 bases, respectively. We evaluate encapsulation efficiency as the percentage of input RNA encapsulated in the final LNP product (EEinput%), which shows discrepancy with the traditional calculation of encapsulation efficiency (EE%). EEinput% is shown to be < 50% for all formulations tested, when EE% is consistently > 85%. We also compared formulations for LNP size (Z-average) and polydispersity index (PDI). LNP size does not appear to be strongly influenced by cargo size, which is a counterintuitive finding. Thoughtful characterization of LNPs, in parallel with consideration of in vitro or in vivo behavior, will guide design and optimization for better understanding and improvement of future RNA therapeutics.

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Section: Encapsulation Efficiency Based On Input Rna Concentrationmentioning

confidence: 99%

A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient

Schober,

Story,

Arya

2024

Sci Rep

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“…As an emerging cancer therapy, mRNA vaccines face multiple challenges [ 86 , 87 , 88 ]. The stability of mRNA vaccines is a major concern.…”

Section: Mrna Vaccines and Tumor Immunitymentioning

confidence: 99%

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

Wu,

Li,

Qian

et al. 2024

Vaccines

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In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells in cancer therapy has become a strategy of great research interest. mRNA vaccines are a potential choice for tumor immunotherapy, due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery carrier, and their structural stability and biocompatibility make them an effective means for delivering mRNA to specific targets. This study summarizes the research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity, and targeting is discussed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy, as well as to provide more effective treatment plans for patients.

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“…It has been found that replacing cholesterol in the LNPs formula with natural phytosterols (such as β‐sitosterol and cholesterol oxide derivatives, 20α‐hydroxycholesterol, and 7α‐hydroxycholesterol) can significantly improve the delivery of mRNA because of its structural branched chain. [ 33 ] Their multilayer structure and shape polymorphism may alter the endomembrane shape or prolong the nucleic acid release time frame.…”

Section: Development Of Lipid Nanoparticlesmentioning

confidence: 99%

Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid

Jia,

Wang,

et al. 2023

Advanced Materials

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Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent the degradation of cargo nucleic acids during blood circulation. Upon entry into the cell, specific components of the lipid nanoparticles can promote the endosomal escape of nucleic acids. These are the basic properties of lipid nanoparticles as nucleic acid carriers. As LNPs exhibit hepatic aggregation characteristics, enhancing targeting out of the liver is a crucial way to improve LNPs administrated in vivo. Meanwhile, endosomal escape of nucleic acids loaded in LNPs is often considered inadequate, and therefore, much effort is devoted to enhancing the intracellular release efficiency of nucleic acids. Here, we concluded different strategies to efficiently deliver nucleic acid delivery from LNPs and investigated their mechanisms. In addition, based on the information on LNPs that are in clinical trials or have completed clinical trials, we discussed the issues that are necessary to be approached in the clinical translation of LNPs, which we hope will shed light on the development of LNP nucleic acid drugs.This article is protected by copyright. All rights reserved

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In Cellulo and In Vivo Comparison of Cholesterol, Beta-Sitosterol and Dioleylphosphatidylethanolamine for Lipid Nanoparticle Formulation of mRNA

Cited by 9 publications

References 64 publications

A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient

A careful look at lipid nanoparticle characterization: analysis of benchmark formulations for encapsulation of RNA cargo size gradient

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity

Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid

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