Lipid nanoparticle-mediated lymph node–targeting delivery of mRNA cancer vaccine elicits robust CD8 ⁺ T cell response

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(34)

Published: Aug. 15, 2022

The targeted delivery of messenger RNA (mRNA) to desired organs remains a great challenge for in vivo applications mRNA technology. For vaccines, the lymph node (LN) is predicted reduce side effects and increase immune response. In this study, we explored an endogenously LN-targeting lipid nanoparticle (LNP) without modification any active targeting ligands developing cancer vaccine. LNP named 113-O12B showed increased specific expression LN compared with formulated ALC-0315, synthetic used COVID-19 vaccine Comirnaty. CD8 + T cell response encoded full-length ovalbumin (OVA) model antigen. As result, protective therapeutic effect OVA-encoding on OVA-antigen–bearing B16F10 melanoma was also improved. Moreover, encapsulated TRP-2 peptide (TRP2 180–188 )–encoding exhibited excellent tumor inhibition, complete 40% regular when combined anti–programmed death-1 (PD-1) therapy, revealing broad application from protein antigens. All treated mice long-term memory, hindering occurrence metastatic nodules lung rechallenging experiments that followed. enhanced antitumor efficacy system shows potential as universal platform next generation vaccines.

Language: Английский

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

ACS Materials Au, Journal Year: 2023, Volume and Issue: 3(6), P. 600 - 619

Published: Aug. 21, 2023

Over the past decade, 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 outcomes, thus gaining substantial interest in preclinical clinical research. In this review, we introduce main types LNPs used formulations such liposomes, nanoemulsions, solid lipid nanoparticles, nanostructured carriers, polymer hybrid focusing on their physicochemical properties potential. We discuss computational studies modeling techniques to enhance understanding how interact with cargo predict effectiveness interactions applications. also analyze benefits drawbacks various LNP production nanoprecipitation, emulsification, evaporation, thin film hydration, microfluidic-based methods, an impingement jet mixer. Additionally, major challenges associated industrial development, including stability sterilization, storage, regulatory compliance, reproducibility, quality control. Overcoming facilitating compliance represent key steps toward LNP's successful commercialization translation into settings.

Language: Английский

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mRNA-based therapeutics: looking beyond COVID-19 vaccines

The Lancet, Journal Year: 2024, Volume and Issue: 403(10432), P. 1192 - 1204

Published: March 1, 2024

Language: Английский

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Recent Advances in the Lipid Nanoparticle-Mediated Delivery of mRNA Vaccines

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 658 - 658

Published: March 14, 2023

Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for highly efficient in vivo delivery exogenous mRNA, particularly COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent advances insights design LNPs, well their composition properties, with a subsequent discussion on development vaccines. particular, are critical drivers complexing mRNA delivery, role vaccines is discussed detail. Furthermore, use effective vehicles vaccination, genome editing, protein replacement therapy explained. Finally, expert opinion discussed, which may address future challenges developing using based novel set lipids. Developing systems improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.

Language: Английский

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Recent Advancement in mRNA Vaccine Development and Applications

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(7), P. 1972 - 1972

Published: July 18, 2023

Messenger RNA (mRNA) vaccine development for preventive and therapeutic applications has evolved rapidly over the last decade. The mRVNA proven efficacy in various applications, including infectious disease, immunotherapy, genetic disorders, regenerative medicine, cancer. Many mRNA vaccines have made it to clinical trials, a couple obtained FDA approval. This emerging approach several advantages conventional methods: safety; efficacy; adaptability; bulk production; cost-effectiveness. However, is worth mentioning that delivery target site vivo degradation thermal stability are boundaries can alter their outcomes. In this review, we shed light on different types of vaccines, mode action, process optimize overcome limitations. We also explored systems focusing nanoparticle-mediated vaccine. Generally, system plays vital role enhancing stability, biocompatibility, homing desired cells tissues. addition function as vehicle, they serve compartment shields protects molecules against physical, chemical, biological activities efficiency. Finally, focused future considerations should be attained safer more efficient application underlining disadvantages current vaccines.

Language: Английский

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Knife’s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(7), P. 1305 - 1313

Published: July 10, 2023

Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in development therapeutics and vaccines. During COVID-19 pandemic, two mRNA vaccines were developed approved record-breaking time, revolutionizing vaccine landscape. Although first-generation demonstrated over 90% efficacy, alongside strong immunogenicity humoral cell-mediated immune responses, their durability has lagged compared long-lived vaccines, such as yellow fever vaccine. worldwide vaccination campaigns saved lives estimated tens millions, side effects, ranging from mild reactogenicity rare severe diseases, reported. This review provides an overview mechanistic insights into responses adverse effects documented primarily for Furthermore, we discuss perspectives this promising platform challenges balancing effects.

Language: Английский

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Nanocarriers for cancer nano-immunotherapy

Drug Delivery and Translational Research, Journal Year: 2022, Volume and Issue: 13(7), P. 1936 - 1954

Published: Oct. 3, 2022

Language: Английский

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Nanomaterials for mRNA‐based therapeutics: Challenges and opportunities

Bioengineering & Translational Medicine, Journal Year: 2023, Volume and Issue: 8(3)

Published: Jan. 29, 2023

Abstract Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into host need to enter nucleus for transfection, it can be expressed even nondividing cells. Therefore, mRNA‐based therapeutics provide a promising strategy clinical treatment. However, efficient safe delivery remains crucial constraint application therapeutics. Although stability tolerability enhanced by directly retouching structure, there is still an urgent improve mRNA. Recently, significant progress has been made nanobiotechnology, providing tools nanocarriers. Nano‐drug system used loading, protecting, releasing biological microenvironment stimulate translation develop effective intervention strategies. present review, we summarized concept emerging nanomaterials latest enhancing function mRNA, primarily focusing on role exosomes delivery. Moreover, outlined its applications so far. Finally, key obstacles nanocarriers are emphasized, strategies overcome these proposed. Collectively, nano‐design materials exert functions specific applications, new perception next‐generation nanomaterials, thus revolution technology.

Language: Английский

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The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 690 - 690

Published: March 17, 2023

This Review initiates a wide-ranging discussion over 2023 by selecting and exploring core themes to be investigated more deeply in papers submitted the Vaccines Special Issue on “Future of Epidemic Pandemic Serve Global Public Health Needs”. To tackle SARS-CoV-2 pandemic, an acceleration vaccine development across different technology platforms resulted emergency use authorization multiple vaccines less than year. Despite this record speed, many limitations surfaced including unequal access products technologies, regulatory hurdles, restrictions flow intellectual property needed develop manufacture vaccines, clinical trials challenges, that did not curtail or prevent transmission, unsustainable strategies for dealing with variants, distorted allocation funding favour dominant companies affluent countries. Key future epidemic pandemic responses will sustainable, global-public-health-driven manufacturing based equitable platform decentralised localised innovation, developers manufacturers, especially low- middle-income countries (LMICs). There is talk flexible, modular preparedness, pools non-exclusive global licensing agreements exchange fair compensation, WHO-supported transfer hubs spokes, creation prototypes ready phase I/II trials, etc. However, all these concepts face extraordinary challenges shaped current commercial incentives, unwillingness pharmaceutical governments share know-how, precariousness building capacity solely COVID-19 focus large-scale rather small-scale rapid-response innovation stop outbreaks when where they occur, inability resource-limited afford next-generation their national programmes. Once high subsidies are gone interest has waned, sustaining capability interpandemic periods require capabilities regions world just “pandemic vaccines”. philanthropic investments need leverage enforceable commitments critical so everywhere can establish scale up capability. only happen if we question prior assumptions learn lessons offered pandemic. We invite submissions special issue, which hope help guide towards research, development, ecosystem better balances integrates scientific, trial, regulatory, interests puts public health needs first.

Language: Английский

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Vaccines’ New Era-RNA Vaccine

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1760 - 1760

Published: Aug. 18, 2023

RNA vaccines, including conventional messenger (mRNA) circular (circRNA) and self-amplifying (saRNA) have ushered in a promising future revolutionized vaccine development. The success of mRNA vaccines combating the COVID-19 pandemic caused by SARS-CoV-2 virus that emerged 2019 has highlighted potential vaccines. These possess several advantages, such as high efficacy, adaptability, simplicity antigen design, ability to induce both humoral cellular immunity. They also offer rapid cost-effective manufacturing, flexibility target emerging or mutant pathogens approach for clearing immunotolerant microbes targeting bacterial parasitic survival mechanisms. self-adjuvant effect mRNA-lipid nanoparticle (LNP) formulations further enhances However, some challenges need be addressed. include technology’s immaturity, research expenses, limited duration antibody response, instability, low efficiency circRNA cyclization, production double-stranded side product. factors hinder widespread adoption utilization particularly developing countries. This review provides comprehensive overview mRNA, circRNA, saRNA infectious diseases while discussing their development, current applications, challenges.

Language: Английский

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