Advances and applications of RNA vaccines in tumor treatment

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 9, 2024

Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives conventional vaccine therapy due their high efficiency, rapid development capability, and potential for low-cost manufacturing safe drug delivery. mainly include mRNA, circular (circRNA), Self-amplifying mRNA(SAM). Different platforms different tumors shown encouraging results in animal human models. This review comprehensively describes the advances applications antitumor therapy. Future directions extending this platform a wide range therapeutic uses are also discussed.

Language: Английский

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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 20, 2024

Abstract This study aimed to develop a pan-genotypic and multifunctional small interfering RNA (siRNA) against hepatitis B virus (HBV) with an efficient delivery system for treating chronic (CHB), explore combined interference (RNAi) immune modulatory modalities better viral control. Twenty synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed evaluated. The lipid nanoparticle (LNP) formulation was optimized by adopting HO-PEG 2000 -DMG modifying molar ratio of traditional polyethylene glycol (PEG) in LNP prescriptions. efficacy safety this delivering siHBV (tLNP/siHBV) along mouse IL-2 (mIL-2) mRNA (tLNP/siHBVIL2) evaluated rAAV-HBV1.3 model. A siRNA combination (terms “siHBV”) genotypic coverage 98.55% selected, chemically modified, encapsulated within (tLNP) high security fabricate therapeutic CHB. results revealed that tLNP/siHBV significantly reduced expression antigens DNA (up 3log 10 reduction; vs PBS) dose- time-dependent manners at single-dose or multi-dose frequencies, satisfactory profiles. Further studies showed tLNP/siHBVIL2 enables additive antigenic control virus, via introducing potent HBsAg clearance through RNAi triggering strong HBV-specific CD4 + CD8 T cell responses expressed mIL-2 protein. By tLNP as nucleic acid nanocarriers, co-delivery synergistic HBV, thus offering promising translational strategy

Language: Английский

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Optimizing mRNA-Loaded Lipid Nanoparticles as a Potential Tool for Protein-Replacement Therapy

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 771 - 771

Published: June 6, 2024

Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform treating metabolic diseases. Four distinct lipid mixes (LMs) formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability homogeneity with mean size of 75 90 nm, confirmed cryo-TEM SAXS studies. High encapsulation (95–100%) was achieved. effectively delivered EGFP-encoding HepG2 DC2.4 cell lines. induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs), revealing that LM1, LM2, 1.5- 4-fold increases in IL-8, TNF-α, MCP-1 levels, while showed minimal changes. Reporter expression observed LNP-treated PBMCs. Hemotoxicity studies formulation biocompatibility values below 2%. In vivo biodistribution mice post intramuscular injection significant expression, mainly the liver. The modification LNP components influenced reactogenicity, inflammatory response, offering promising selecting less reactogenic carriers suitable repetitive dosing disease treatment.

Language: Английский

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Current landscape of mRNA technologies and delivery systems for new modality therapeutics

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Sept. 10, 2024

Abstract Realizing the immense clinical potential of mRNA-based drugs will require continued development methods to safely deliver bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized improve mRNA delivery protect cargo from extracellular degradation. Encapsulation in was an essential factor successful application vaccines, which conclusively demonstrated technology's yield approved medicines. review, we begin by describing current advances modifications, design novel lipids nanoparticle components for drugs. Then, summarize key points pertaining preclinical therapeutics. Finally, cover topics related targeted systems, including endosomal escape targeting immune cells, tumors organs use vaccines new treatment modalities human diseases.

Language: Английский

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Opportunities in Therapeutic mRNA Stabilization: Sequence, Structure, Adjuvants and Vectors

Advanced Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract The reliance of current COVID‐19 mRNA lipid nanoparticles on cold storage increases the cost and reduces access to vaccines. As therapeutic expands other clinical opportunities, better methods stabilize medicines during shipping, storage, delivery are needed. This work reviews advances in design with a focus codon optimization, chemical modifications, RNA structures. Additionally, technologies promoting nanoparticle stabilization including ionizable lipids, excipients, lyophilization, inorganic systems reviewed. Application emerging improve may produce stable, “off‐the‐shelf” therapeutics that can be accessed worldwide.

Language: Английский

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Self-assembly of paclitaxel derivative and fructose as a potent inducer of immunogenic cell death to enhance cancer immunotherapy

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101793 - 101793

Published: April 23, 2025

Immunotherapy shows promise for tumor control but is limited by low response rates. Paclitaxel (PTX) induces immunogenic cell death (ICD), yet conventional delivery systems face challenges like drug loading and insufficient intracellular accumulation, reducing ICD efficacy. Small-molecule self-assembled PTX nanoparticles offer a promising solution due to high dose delivery. In this study, was conjugated with phenylboronic acid (PBA) form the derivative PTX-PBA, which spontaneously fructose into (PTX-PBA-Fru NPs). These exhibited uniform size of 107.8 ± 2.9 nm, PDI 0.064 0.042, zeta potential -12.2 0.9 mV, spherical morphology. 4T1 tumor-bearing mice, PTX-PBA-Fru NPs significantly enhanced inhibition (p < 0.001) increased body weight 0.05). No allergic reactions in healthy Balb/c mice maximum tolerated intravenous reached 200 mg/kg, underscoring its favorable safety profile NPs. The effects induced NPs, when combined immunomodulator resiquimod (R848), elicited robust anti-tumor immune response. This combination therapy effectively remodeled immunosuppressive microenvironment achieved 37.5 % eradication rate. Moreover, it established long-term memory, providing protection against re-challenge. novel formulation demonstrates strong effects, safety, clinical R848-based immunotherapy.

Language: Английский

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Replacing PEG-Lipid with Amphiphilic Polycarbonates in mRNA-Loaded Lipid Nanoparticles: Impact of Polycarbonate Structure on Physicochemical and Transfection Properties

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: May 10, 2025

Since the remarkable breakthrough of COVID-19 mRNA vaccines, lipid nanoparticles (LNPs) have gained substantial attention as most cutting-edge clinical formulations for delivery. PEGylated (PEG-lipid) has been regarded an essential constituent LNPs that helps to prolong their systemic circulation by preventing particle aggregation in blood and sequestration mononuclear phagocyte system. Herein, we synthesized a series mRNA-loaded replacing ALC-0159 (a PEG-lipid used Comirnaty formulation) with amphiphilic PEG-polycarbonate diblock copolymers (PC-HNPs). Interestingly, variations polycarbonate block length structure significantly influenced encapsulation efficiency, transfection potency, colloidal stability, PEG shedding rate PC-HNPs. In vivo ex bioluminescence imaging revealed upon subcutaneous administration mice, leading candidate PC3-HNP achieved lymph node accumulation comparable conventional ALC-0159-based LNP formulation while avoiding undesirable liver accumulation. Our findings may provide valuable information construction next-generation nanocarriers effective

Language: Английский

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The benefits of emerging alternatives to PEG for lipid nanoparticle RNA delivery systems

Nanomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 3

Published: May 10, 2025

Language: Английский

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Effect of Anti-PEG Antibody on Immune Response of mRNA-Loaded Lipid Nanoparticles

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccines have been approved for use to combat coronavirus disease 2019 (COVID-19). The mRNA-LNPs contain PEG-conjugated lipids. Clinical studies reported that induce the production of anti-PEG antibodies, but antibodies do not affect neutralizing antibodies. However, detailed influence on mRNA-LNP remains unclear. Therefore, in this study, we prepared ovalbumin (OVA) as a model antigen-encoding mRNA-loaded LNP (mRNA-OVA-LNP), and determined whether could antigen-specific immune response mRNA-OVA-LNP vaccination mice pretreated with PEG-modified liposomes After intramuscular (i.m.) injection mRNA-LNP, did change expression protein or induction cytokine cellular slightly increase Furthermore, repeated i.m. induced IgM IgG. Our results suggest induces priming is notably affected by

Language: Английский

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Microparticle and nanoparticle-based influenza vaccines

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 880 - 898

Published: Nov. 6, 2024

Language: Английский

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