Abstract

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

Highlights

  • Messenger RNA-based vaccines have shown promise as techniques for the development of vaccines against infectious diseases and several types of cancer since the2000s

  • Hassett et al assessed a group of proprietary biodegradable ionizable lipids in addition to distearoylphosphatidylcholine (DSPC), cholesterol, and polyethylene glycol (PEG) lipid to develop lipid nanoparticles encapsulating Messenger RNA (mRNA) encoding firefly luciferase and the H10N8 influenza hemagglutinin antigen

  • Core/lipid-shell nanoparticle was developed as a delivery system. This delivery system allows for efficient adjuvant loading of hydrophobic Toll-like receptor 7 (TLR7) adjuvants such as gardiquimod into the poly(lactic-co-glycolic acid) (PLGA) core, while the lipid shell allows the complexation of mRNA

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Summary

Introduction

Messenger RNA (mRNA)-based vaccines have shown promise as techniques for the development of vaccines against infectious diseases and several types of cancer since the. Local intranodal injection of RNA leads to the effective activation of a specific immune response [17,18,19], delivery systems are crucial for successful in vivo delivery of mRNA to the site of action and for large-scale preventive vaccinations. Non-viral victors include nanodelivery systems (Figure 3, Table 2): lipid-based, polymer-based, and lipid–polymer hybrid nanoparticles [28,29,30,31,32,33,34] These are currently the most favored methods for delivering mRNA, as they are considered safe, stable, and low-cost, and provide highly efficient transfection. The aim of the rest of this review is to discuss the recent applications of biodegradable nanoparticles that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases. MRNA: messenger RNA; SAM RNA: self-amplifying RNA; DSPC: distearoylphosphatidylcholine; PEG: polyethylene glycol; COVID-19: coronavirus disease 2019; DC-Chol: 3ß-[N-(N’,N’-dimethylaminoethane)carbamoyl]cholesterol; DDA: dimethyldioctadecylammonium; DOTAP: 1,2-dioleoyl-3-trimethylammonium-propane; DMTAP: 1,2-dimyristoyl-3-trimethylammonium-propane; DSTAP: 1,2-stearoyl-3trimethylammonium-propane; DOBAQ: N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis (oleoyloxy)propan-1-aminium; DMG-PEG2000: 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; DSPE-mPEG2000: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy (polyethylene glycol)-2000); OVA: ovalbumin

Lipid-Based Nanodelivery Systems
Lipid-Nanoparticle-Based Nanodelivery Systems
Lipoplex-Based Nanodelivery Systems
Polymer-Based Nanodelivery Systems
Polyplex-Based Nanodelivery Systems
Cationic Micelle-Based Nanodelivery Systems
Dendrimer-Based Nanodelivery Systems
Nanogel-Based Nanodelivery Systems
Hybrid-Based Nanodelivery Systems
Cationic Nanoemulsion-Based Nanodelivery Systems
Lipopolyplex-Based Nanodelivery Systems
Conclusions and Future Perspectives
Findings
A Novel Amino Lipid Series for mRNA Delivery
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