During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this review, we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufactured and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.

With the mass vaccination program for COVID-19 mRNA vaccines, there has been sufficient real-world study (RWS) on the topic to summarize their safety in the total population and in immunocompromised (IC) patients who were excluded from phase 3 clinical trials. We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 mRNA vaccines, with a total of 5,132,799 subjects from 122 articles. In the case of the total population vaccinated with first, second, and third doses, the pooled incidence of any adverse events (AEs) was 62.20%, 70.39%, and 58.60%; that of any local AEs was 52.03%, 47.99%, and 65.00%; that of any systemic AEs was 29.07%, 47.86%, and 32.71%. Among the immunocompromised patients, the pooled odds ratio of any AEs, any local AEs, and systemic AEs were slightly lower than or similar to those of the healthy controls at 0.60 (95% CI: 0.33–1.11), 0.19 (95% CI: 0.10–0.37), and 0.36 (95% CI: 0.25–0.54), with pooled incidences of 51.95%, 38.82%, and 31.00%, respectively. The spectrum of AEs associated with the vaccines was broad, but most AEs were transient, self-limiting, and mild to moderate. Moreover, younger adults, women, and people with prior SARS-CoV-2 infection were more likely to experience AEs.

Introduction: In this study, we report on the development of an effective delivery system for siRNAs; a novel cell-penetrating peptide (CPP), T9(dR), obtained from transportan (TP), was used for in vivo and in vitro testing. Methods: In this study, toxicity of T9(dR) and TP and efficient delivery of siRNA were tested in 293T, MDCK, RAW, and A549 cells. Furthermore, T9(dR)- and TP-delivered siRNAs against nucleoprotein (NP) gene segment of influenza virus (siNP) were studied in both cell lines and mice. Results: Gel retardation showed that T9(dR) effectively condensed siRNA into nanoparticles sized between 350 and 550 nm when the mole ratio of T9(dR) to siRNA was ≥4:1. In vitro studies demonstrated that T9(dR) successfully delivered siRNA with low cellular toxicity into several cell lines. It was also observed that T9(dR)-delivered siRNAs inhibited replication of influenza virus more efficiently as compared to that delivered by TP into the MDCK and A549 cells. It was also noticed that when given a combined tail vein injection of siNP and T9(dR) or TP, all mice in the 50 nmol siNP group infected with PR8 influenza virus survived and showed weight recovery at 2 weeks post-infection. Conclusion: This study indicates that T9(dR) is a promising siRNA delivery tool with potential application for nucleotide drug delivery.

Objectives: To elucidate the expression levels and prognostic value of the Lipoyltransferase 2 (LIPT2) gene in a pan-cancer view. Methodology: Our study comprehensively investigated the role of LIPT2 in pan-cancer, combining bioinformatics analyses with experimental validations. Results: Analysis of LIPT2 mRNA expression across various cancers revealed a significant up-regulation in 18 tumor types and down-regulation in 8 types, indicating its diverse involvement. Prognostic assessment demonstrated a correlation between elevated LIPT2 expression and poorer outcomes in Overall Survival (OS) and Disease-Free Survival (DFS), particularly in Glioblastoma Multiforme (GBM), Liver Hepatocellular Carcinoma (LIHC), and Pheochromocytoma and Paraganglioma (PCPG). Protein expression analysis in GBM, LIHC, and PCPG affirmed a consistent increase in LIPT2 levels compared to normal tissues. Examining the methylation status in GBM, LIHC, and PCPG, we found reduced promoter methylation levels in tumor samples, suggesting a potential influence on LIPT2 function. Genetic mutation analysis using cBioPortal indicated a low mutation frequency (< 2%) in LIPT2 across GBM, LIHC, and PCPG. Immune correlation analysis unveiled a positive association between LIPT2 expression and infiltration levels of immune cells in GBM, LIHC, and PCPG. Single-cell analysis illustrated LIPT2’s positive correlation with functional states, including angiogenesis and inflammation. Enrichment analysis identified LIPT2-associated processes and pathways, providing insights into its potential molecular mechanisms. Drug sensitivity analysis demonstrated that elevated LIPT2 expression conferred resistance to multiple compounds, while lower expression increased sensitivity. Finally, RT-qPCR validation in HCC cell lines confirmed the heightened expression of LIPT2 compared to a control cell line, reinforcing the bioinformatics findings. Conclusion: Overall, our study highlights LIPT2 as a versatile player in cancer, influencing diverse aspects from molecular processes to clinical outcomes across different cancer types.