Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Co-administration of GM-CSF expressing RNA is a powerful tool to enhance potency of SAM-based vaccines

Self-amplifying mRNAs (SAM)-based vaccines have been shown to induce a robust immune response in various animal species against both viral and bacterial pathogens. Due to their synthetic nature and to the versatility of the manufacturing process, SAM technology may represent an attractive solution for rapidly producing novel vaccines, which is particularly critical in case of pandemic infections or diseases mediated by newly emerging pathogens. Recent published data support the hypothesis that Antigen Presenting Cells (APCs) are responsible for CD8+ T-cell priming after SAM vaccination, suggesting cross-priming as the key mechanism for antigen presentation by SAM vaccines. In our study we investigated the possibility to enhance the immune response induced in mice by a single immunization with SAM by increasing the recruitment of APCs at the site of injection. To enhance SAM immunogenicity, we selected murine granulocyte-macrophage colony-stimulating factor (GM-CSF) as a model chemoattractant for APCs, and developed a SAM-GM-CSF vector. We evaluated whether the use of SAM-GM-CSF in combination with a SAM construct encoding the Influenza A virus nucleoprotein (NP) would lead to an increase of APC recruitment and NP-specific immune response. We indeed observed that the administration of SAM-GM-CSF enhances the recruitment of APCs at the injection site. Consistently with our hypothesis, co-administration of SAM-GM-CSF with SAM-NP significantly improved the magnitude of NP-specific CD8+ T-cell response both in terms of frequency of cytotoxic antigen-specific CD8+ T-cells and their functional activity in vivo. Furthermore, co-immunization with SAM-GM-CSF and SAM-NP provided an increase in protection against a lethal challenge with influenza virus. In conclusion, we demonstrated that increased recruitment of APCs at the site of injection is associated with an enhanced effectiveness of SAM vaccination and might be a powerful tool to potentiate the efficacy of RNA vaccination.