mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

Xu, Shuqin; Yang, Kun; Li, Rose; Zhang, Lu

doi:10.3390/ijms21186582

Cited by 235 publications

(239 citation statements)

References 193 publications

(332 reference statements)

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“…Briefly, the expressed proteins (EPs) released from the host cells are captured by the antigen-presenting cells (APCs), primarily dendritic cells (DCs). The EPs are subsequently degraded to antigenic peptides within the cells and presented to cytotoxic T lymphocytes via the major histocompatibility complex (MHC) I pathway, and to B-cells via the MHC II pathway ( 12 ). Therefore, targeting mRNA directly to APCs, mainly DCs, is the most effective approach to immunization.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

2021

Pharm Res

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The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA (mRNA)-based vaccines have become the front-runners because of their safety profiles, precise and reproducible immune response with more cost-effective and faster production than other types of vaccines. However, the physicochemical properties of naked mRNA necessitate innovative delivery technologies to ferry these ‘messengers’ to ribosomes inside cells by crossing various barriers and subsequently induce an immune response. Intracellular delivery followed by endosomal escape represents the key strategies for cytoplasmic delivery of mRNA vaccines to the target. This Perspective provides insights into how state-of-the-art nanotechnology helps break the delivery barriers and advance the development of mRNA vaccines. The challenges remaining and future perspectives are outlined.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

2021

Pharm Res

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“…However, unprotected mRNA is highly unstable under physiological conditions because of its sensitivity toward catalytic hydrolysis by nucleases [ 7 ]. It is not efficiently internalized in its free form, mainly due to its large size (300–5000 kDa; 1–15 kB) [ 8 , 9 ] and negative charge [ 10 , 11 ]. In fact, it has been speculated that the cellular uptake rate and cytoplasmic transfer of naked mRNA is less than 1 in 10,000 molecules of the initial mRNA input [ 8 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

et al. 2021

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The approval of two mRNA vaccines as urgent prophylactic treatments against Covid-19 made them a realistic alternative to conventional vaccination methods. However, naked mRNA is rapidly degraded by the body and cannot effectively penetrate cells. Vectors capable of addressing these issues while allowing endosomal escape are therefore needed. To date, the most widely used vectors for this purpose have been lipid-based vectors. Thus, we have designed an innovative vector called LipoParticles (LP) consisting of poly(lactic) acid (PLA) nanoparticles coated with a 15/85 mol/mol DSPC/DOTAP lipid membrane. An in vitro investigation was carried out to examine whether the incorporation of a solid core offered added value compared to liposomes alone. To that end, a formulation strategy that we have named particulate layer-by-layer (pLbL) was used. This method permitted the adsorption of nucleic acids on the surface of LP (mainly by means of electrostatic interactions through the addition of LAH4-L1 peptide), allowing both cellular penetration and endosomal escape. After a thorough characterization of size, size distribution, and surface charge— and a complexation assessment of each vector—their transfection capacity and cytotoxicity (on antigenic presenting cells, namely DC2.4, and epithelial HeLa cells) were compared. LP have been shown to be significantly better transfecting agents than liposomes through pLbL formulation on both HeLa and DC 2.4 cells. These data illustrate the added value of a solid particulate core inside a lipid membrane, which is expected to rigidify the final assemblies and makes them less prone to early loss of mRNA. In addition, this assembly promoted not only efficient delivery of mRNA, but also of plasmid DNA, making it a versatile nucleic acid carrier that could be used for various vaccine applications. Finally, if the addition of the LAH4-L1 peptide systematically leads to toxicity of the pLbL formulation on DC 2.4 cells, the optimization of the nucleic acid/LAH4-L1 peptide mass ratio becomes an interesting strategy—essentially reducing the peptide intake to limit its cytotoxicity while maintaining a relevant transfection efficiency.

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“…The mRNA vaccine is a promising drug for cancer prevention and treatment [120]. In contrast to DNA vaccines, mRNA vaccines can express the target protein directly, thus avoiding the side effects associated with various mutations during transcription [121].…”

Section: Nanoparticle-based Strategies For Melanoma Mrna Vaccine Therapymentioning

confidence: 99%

Nanocarrier-Based Drug Delivery for Melanoma Therapeutics

Song

Liu

Chen

et al. 2021

IJMS

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Melanoma, as a tumor cell derived from melanocyte transformation, has the characteristics of malignant proliferation, high metastasis, rapid recurrence, and a low survival rate. Traditional therapy has many shortcomings, including drug side effects and poor patient compliance, and so on. Therefore, the development of an effective treatment is necessary. Currently, nanotechnologies are a promising oncology treatment strategy because of their ability to effectively deliver drugs and other bioactive molecules to targeted tissues with low toxicity, thereby improving the clinical efficacy of cancer therapy. In this review, the application of nanotechnology in the treatment of melanoma is reviewed and discussed. First, the pathogenesis and molecular targets of melanoma are elucidated, and the current clinical treatment strategies and deficiencies of melanoma are then introduced. Following this, we discuss the main features of developing efficient nanosystems and introduce the latest reports in the literature on nanoparticles for the treatment of melanoma. Subsequently, we review and discuss the application of nanoparticles in chemotherapeutic agents, immunotherapy, mRNA vaccines, and photothermal therapy, as well as the potential of nanotechnology in the early diagnosis of melanoma.

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mRNA Vaccine Era—Mechanisms, Drug Platform and Clinical Prospection

Cited by 235 publications

References 193 publications

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

Nanoparticle-Mediated Cytoplasmic Delivery of Messenger RNA Vaccines: Challenges and Future Perspectives

LipoParticles: Lipid-Coated PLA Nanoparticles Enhanced In Vitro mRNA Transfection Compared to Liposomes

Nanocarrier-Based Drug Delivery for Melanoma Therapeutics

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