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  • Kinetics of RNA-LNP delivery and protein expression
    Kinetics of RNA-LNP delivery and protein expression 2025-07-18
    Review Eur J Pharm Biopharm. 2024 Apr:197:114222. doi: 10.1016/j.ejpb.2024.114222. Epub 2024 Feb 20. Kinetics of RNA-LNP delivery and protein expression Abstract Lipid nanoparticles (LNPs) employing ionizable lipids are the most advanced technology for delivery of RNA, most notably mRNA, to cells. LNPs represent well-defined core-shell particles with efficient nucleic acid encapsulation, low immunogenicity and enhanced efficacy. While much is known about the structure and activity of LNPs, less attention is given to the timing of LNP uptake, cytosolic transfer and protein expression. However, LNP kinetics is a key factor determining delivery efficiency. Hence quantitative insight into the multi-cascaded pathway of LNPs is of interest to elucidate the mechanism of delivery. Here, we review experiments as well as theoretical modeling of the timing of LNP uptake, mRNA-release and protein expression. We describe LNP delivery as a sequence of stochastic transfer processes and review a mathematical model of subsequent protein translation from mRNA. We compile probabilities and numbers obtained from time resolved microscopy. Specifically, live-cell imaging on single cell arrays (LISCA) allows for high-throughput acquisition of thousands of individual GFP reporter expression time courses. The traces yield the distribution of mRNA life-times, expression rates and expression onset. Correlation analysis reveals an inverse dependence of gene expression efficiency and transfection onset-times. Finally, we discuss why timing of mRNA release is critical in the context of codelivery of multiple nucleic acid species as in the case of mRNA co-expression or CRISPR/Cas gene editing. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com
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  • Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety
    Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety 2025-07-15
    Review Biomedicines. 2021 May 10;9(5):530. doi: 10.3390/biomedicines9050530. Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety Abstract Lipid nanoparticle (LNP) formulated messenger RNA-based (LNP-mRNA) vaccines came into the spotlight as the first vaccines against SARS-CoV-2 virus to be applied worldwide. Long-known benefits of mRNA-based technologies consisting of relatively simple and fast engineering of mRNA encoding for antigens and proteins of interest, no genomic integration, and fast and efficient manufacturing process compared with other biologics have been verified, thus establishing a basis for a broad range of applications. The intrinsic immunogenicity of LNP formulated in vitro transcribed (IVT) mRNA is beneficial to the LNP-mRNA vaccines. However, avoiding immune activation is critical for therapeutic applications of LNP-mRNA for protein replacement where targeted mRNA expression and repetitive administration of high doses for a lifetime are required. This review summarizes our current understanding of immune activation induced by mRNA, IVT byproducts, and LNP. It gives a comprehensive overview of the present status of preclinical and clinical studies in which LNP-mRNA is used for protein replacement and treatment of rare diseases with an emphasis on safety. Moreover, the review outlines innovations and strategies to advance pharmacology and safety of LNP-mRNA for non-immunotherapy applications. Keywords: LNP-mRNA; RNA protein replacement therapy; cytokines; efficacy; in vitro transcription (IVT); innate immunity; lipid nanoparticle; non-immunotherapy applications; rare disease; safety. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com
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  • The role of lipid components in lipid nanoparticles for vaccines and gene therapy
    The role of lipid components in lipid nanoparticles for vaccines and gene therapy 2025-07-11
    Review Adv Drug Deliv Rev. 2022 Sep:188:114416. doi: 10.1016/j.addr.2022.114416. Epub 2022 Jul 3. The role of lipid components in lipid nanoparticles for vaccines and gene therapy Abstract Lipid nanoparticles (LNPs) play an important role in mRNA vaccines against COVID-19. In addition, many preclinical and clinical studies, including the siRNA-LNP product, Onpattro®, highlight that LNPs unlock the potential of nucleic acid-based therapies and vaccines. To understand what is key to the success of LNPs, we need to understand the role of the building blocks that constitute them. In this Review, we discuss what each lipid component adds to the LNP delivery platform in terms of size, structure, stability, apparent pKa, nucleic acid encapsulation efficiency, cellular uptake, and endosomal escape. To explore this, we present findings from the liposome field as well as from landmark and recent articles in the LNP literature. We also discuss challenges and strategies related to in vitro/in vivo studies of LNPs based on fluorescence readouts, immunogenicity/reactogenicity, and LNP delivery beyond the liver. How these fundamental challenges are pursued, including what lipid components are added and combined, will likely determine the scope of LNP-based gene therapies and vaccines for treating various diseases. Keywords: Drug delivery; Helper lipid; Ionizable lipid; LNP; Lipid nanoparticles; Nucleic acid; PEGylated lipid; Physicochemical properties; Targeting; pK(a). For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com
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  • Chemistry of Lipid Nanoparticles for RNA Delivery
    Chemistry of Lipid Nanoparticles for RNA Delivery 2025-07-08
    Review Acc Chem Res. 2022 Jan 4;55(1):2-12. doi: 10.1021/acs.accounts.1c00544. Epub 2021 Dec 1. Chemistry of Lipid Nanoparticles for RNA Delivery Abstract Lipid nanoparticles (LNPs) are a type of lipid vesicles that possess a homogeneous lipid core. These vesicles are widely used in small-molecule drug and nucleic acid delivery and recently gained much attention because of their remarkable success as a delivery platform for COVID-19 mRNA vaccines. Nonetheless, the utility of transient protein expression induced by mRNA extends far beyond vaccines against infectious diseases─they also hold promise as cancer vaccines, protein replacement therapies, and gene editing components for rare genetic diseases. However, naked mRNA is inherently unstable and prone to rapid degradation by nucleases and self-hydrolysis. Encapsulation of mRNA within LNPs protects mRNA from extracellular ribonucleases and assists with intracellular mRNA delivery.In this Account, we discuss the core features of LNPs for RNA delivery. We focus our attention on LNPs designed to deliver mRNA; however, we also include examples of siRNA-LNP delivery where appropriate to highlight the commonalities and the dissimilarities due to the nucleic acid structure. First, we introduce the concept of LNPs, the advantages and disadvantages of utilizing nucleic acids as therapeutic agents, and the general reasoning behind the molecular makeup of LNPs. We also briefly highlight the most recent clinical successes of LNP-based nucleic acid therapies. Second, we describe the theory and methods of LNP self-assembly. The common idea behind all of the preparation methods is inducing electrostatic interactions between the nucleic acid and charged lipids and promoting nanoparticle growth via hydrophobic interactions. Third, we break down the LNP composition with special attention to the fundamental properties and purposes of each component. This includes the identified molecular design criteria, commercial sourcing, impact on intracellular trafficking, and contribution to the properties of LNPs. One of the key components of LNPs is ionizable lipids, which initiate electrostatic binding with endosomal membranes and facilitate cytosolic release; however, the roles of other lipid components should not be disregarded, as they are associated with stability, clearance, and distribution of LNPs. Fourth, we review the attributes of LNP constructs as a whole that can heavily influence RNA delivery. These attributes are LNP size, charge, internal structure, lipid packing, lipid membrane hydration, stability, and affinity toward biomacromolecules. We also discuss the specific techniques used to examine these attributes and how they can be adjusted. Finally, we offer our perspective on the future of RNA therapies and some questions that remain in the realm of LNP formulation and optimization. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: ...
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  • Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies
    Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies 2025-07-04
    Review Research (Wash D C). 2024 Jun 18:7:0370. doi: 10.34133/research.0370. eCollection 2024. Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies Abstract Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety of diseases. The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences the unlimited medical and therapeutic potential of mRNA technology. Overcoming challenges related to mRNA stability, immunogenicity, and precision targeting has been made possible by recent advancements in lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, and screening principles. Additionally, we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions, cancer immunotherapy, gene editing, and rare-disease medicine. Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics. We explore concerns in the aspects of inadequate extrahepatic targeting efficacy, elevated doses, safety concerns, and challenges of large-scale production procedures. This discussion may offer insights and perspectives on near- and long-term clinical development prospects for LNP-mRNA therapeutics. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com
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  • Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain
    Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain 2025-07-01
    J Control Release. 2022 Aug:348:34-41. doi: 10.1016/j.jconrel.2022.05.042. Epub 2022 Jun 1. Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain Abstract Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA-LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm2, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening. Keywords: Blood-brain barrier (BBB); Focused ultrasound (FUS); Lipid nanoparticles (LNP); Messenger RNA (mRNA); Microbubble. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com
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  • SINOEPG's invitation | CPHI China 2025
    SINOEPG's invitation | CPHI China 2025 June 6,2025.
    Join Us at CPHI China 2025! SINOPEG's booth no. W4F66 Exciting news! CPHI China 2025 is just around the corner, taking place June 24–26 at the Shanghai New International Expo Centre. SINOPEG will be showcasing cutting-edge drug delivery system (DDS) solutions at Booth W4F66. As your trusted partner in specialty chemicals and advanced drug delivery systems, we’re eager to share innovations that drive industry progress. Why visit us? Explore our latest portfolio of PEG derivatives, lipids, and custom synthesis services Discuss tailored solutions for your R&D and manufacturing challenges Connect face-to-face with our technical experts We warmly welcome friends, partners, and industry peers from around the globe to drop by! Let’s collaborate to shape the future of pharma.  Dates: June 24–26, 2025 Venue: Shanghai New International Expo Centre Our Booth: W4F66 (Hall W4) Ready to meet? Simply stop by! 
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  • SINOEPG's invitation | TIDES USA 2025
    SINOEPG's invitation | TIDES USA 2025 May 19,2025.
    Monday Motivation: Let's Kickstart TIDES USA 2025! The wait is almost over—TIDES USA 2025 begins! As the leading event for oligonucleotide and peptide innovation, this is the place to connect with industry pioneers and explore breakthroughs shaping the future of therapeutics. SINOPEG is excited to join the conversation at Booth #613! Whether you're looking to discuss cutting-edge PEGylation technologies, lipid technologies, explore customized solutions, or simply network with our team, we're here to collaborate and inspire. Why stop by? Discover our latest advancements in drug delivery systems. Connect with experts driving precision and innovation. Explore partnerships to accelerate your next-gen therapies. Pro tip: Book a meeting with us in advance or drop by anytime—we'd love to brainstorm how we can support your goals! Let's make this week transformative. See you at Booth #613! https://lnkd.in/gpSNd5si #TIDESUSA2025 #Oligonucleotides #PeptideTherapeutics #DrugDelivery #PEGylation #SINOPEG #InnovationInHealthcare
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