Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines

Kim, Byungji; Hosn, Ryan R.; Remba, Tanaka; Yun, Dongsoo; Li, Na; Abraham, Wuhbet; Melo, Mariane B.; Cortés, Manuel; Li, Bridget; Zhang, Yuebao; Dong, Yizhou; Irvine, Darrell J.

doi:10.1016/j.jconrel.2022.11.022

Cited by 29 publications

(20 citation statements)

References 63 publications

(92 reference statements)

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“…Existing LNP-formulated drugs often necessitate ultracold storage temperatures . For instance, during the COVID-19 pandemic, mRNA-LNP vaccines like Comirnaty (BNT162b2) and Spikevax (mRNA-1273) require storage at ultracold temperatures (−80 and −20 °C, respectively) to ensure their safety and efficacy as per regulatory guidelines .…”

Section: Main Challenges Associated With the Industrial Development O...mentioning

confidence: 99%

“…In conclusion, optimizing the long-term storage of LNPs requires careful consideration and fine-tuning of storage conditions and packaging to ensure their enduring stability and effectiveness. , Moreover, special attention should be devoted to shelf life during formulation design to facilitate the widespread use of LNP products, such as mRNA-LNP vaccines . While challenges related to LNP storage persist, ongoing research and innovation are essential to surmounting these hurdles and making LNP-formulated drugs more accessible and efficacious.…”

Section: Main Challenges Associated With the Industrial Development O...mentioning

confidence: 99%

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Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

Mehta,

Bui,

Yang

et al. 2023

ACS Mater. Au

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Over the past decade, the therapeutic potential of nanomaterials as novel drug delivery systems complementing conventional pharmacology has been widely acknowledged. Among these nanomaterials, lipid-based nanoparticles (LNPs) have shown remarkable pharmacological performance and promising therapeutic outcomes, thus gaining substantial interest in preclinical and clinical research. In this review, we introduce the main types of LNPs used in drug formulations such as liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, and lipid polymer hybrid nanoparticles, focusing on their main physicochemical properties and therapeutic potential. We discuss computational studies and modeling techniques to enhance the understanding of how LNPs interact with therapeutic cargo and to predict the potential effectiveness of such interactions in therapeutic applications. We also analyze the benefits and drawbacks of various LNP production techniques such as nanoprecipitation, emulsification, evaporation, thin film hydration, microfluidic-based methods, and an impingement jet mixer. Additionally, we discuss the major challenges associated with industrial development, including stability and sterilization, storage, regulatory compliance, reproducibility, and quality control. Overcoming these challenges and facilitating regulatory compliance represent the key steps toward LNP’s successful commercialization and translation into clinical settings.

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Section: Main Challenges Associated With the Industrial Development O...mentioning

confidence: 99%

Section: Main Challenges Associated With the Industrial Development O...mentioning

confidence: 99%

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

Mehta,

Bui,

Yang

et al. 2023

ACS Mater. Au

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“…Darrell J. Irvine's team stored LNPs in PBS containing 10% (w/v) sucrose at −20 °C for 30 days and still maintained the stability and in vivo potency of the vaccine. [ 169 ] mRNA‐LNPs can also be lyophilized by adding a lyophilization protectant to maintain its long‐term stability. For example, lyophilization provides at least 18 months of stability at 5 °C for Moderna's Phase II mRNA‐LNPs CMV vaccine (mRNA‐1647).…”

Section: Other Clinical Issuesmentioning

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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“…There are a limited number of published studies on freezing iLNPs. Sugar‐based cryoprotectants, such as sucrose, mannitol and trehalose have been reported, and the selection of buffers and freezing conditions have been investigated (Ball et al., 2017; Henderson et al, 2022; Kafetzis et al., 2023; Kim et al., 2023; Zhao et al., 2020). The optimal conditions reported for freezing mRNA‐iLNPs appears to be variable, depending on the ionizable lipid or lipidoid and RNA cargo.…”

Section: Commentarymentioning

confidence: 99%

mRNA Synthesis and Encapsulation in Ionizable Lipid Nanoparticles

McKenzie,

Minnell,

Ganley

et al. 2023

Current Protocols

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AbstractmRNA vaccines have recently generated significant interest due to their success during the COVID‐19 pandemic. Their success is due to advances in mRNA design and encapsulation into ionizable lipid nanoparticles (iLNPs). This has highlighted the potential for the use of mRNA‐iLNPs in other settings such as cancer, gene therapy, or vaccines for different infectious diseases. Here, we describe the production of mRNA‐iLNPs using commercially available reagents that are suitable for use as vaccines and therapeutics. This article contains detailed protocols for the synthesis of mRNA by in vitro transcription with enzymatic capping and tailing and the encapsulation of the mRNA into iLNPs using the ionizable lipid DLin‐MC3‐DMA. DLin‐MC3‐DMA is often used as a benchmark for new formulations and provides an efficient delivery vehicle for screening mRNA design. The protocol also describes how the formulation can be adapted to other lipids. Finally, a stepwise methodology is presented for the characterization and quality control of mRNA‐iLNPs, including measuring mRNA concentration and encapsulation efficiency, particle size, and zeta potential. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Synthesis of mRNA by in vitro transcription and enzymatic capping and tailingBasic Protocol 2: Encapsulation of mRNA into ionizable lipid nanoparticlesAlternate Protocol: Small‐scale encapsulation of mRNA using preformed vesiclesBasic Protocol 3: Characterization and quality control of mRNA ionizable lipid nanoparticles

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Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines

Cited by 29 publications

References 63 publications

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

Lipid-Based Nanoparticles for Drug/Gene Delivery: An Overview of the Production Techniques and Difficulties Encountered in Their Industrial Development

Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid

mRNA Synthesis and Encapsulation in Ionizable Lipid Nanoparticles

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