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A small but promising clinical study led by Memorial Sloan-Kettering Cancer Center suggests that adding a personalized mRNA vaccine to standard treatment may bring new hope to pancreatic cancer patients. The study followed 16 pancreatic cancer patients. Specifically, in addition to standard treatments such as surgery and chemotherapy, these patients received a customized mRNA vaccine designed using their own tumors. Unlike vaccines that are originally designed to prevent disease, this vaccine is designed to help the patient's own immune system fight cancer.
The blood-brain barrier (BBB) refers to the barrier between plasma and brain cells formed by the walls of brain capillaries and glial cells, and the barrier between plasma and cerebrospinal fluid formed by the choroid plexus, which only allows specific types of molecules to enter brain neurons and other surrounding cells from the bloodstream. The existence of the blood-brain barrier is of great significance in preventing harmful substances from entering the brain from the blood. However, it also prevents the transfer of most small and large molecule drugs (such as peptides, proteins and nucleic acids), severely limiting the treatment of central nervous system diseases (such as neurodegenerative diseases, brain tumors, brain infections and strokes). Although some progress has been made in this field in recent years, we still urgently need technologies that can cross the blood-brain barrier and improve the delivery of biomacromolecule-based therapies to the central nervous system (CNS) through systemic administration.
As an RNA therapy tool, circular mRNA has higher stability and durability than linear mRNA. However, its translation efficiency is low and it mainly relies on the internal ribosome entry site (IRES) to initiate translation. But the IRES-mediated translation efficiency is generally low, which severely limits the application of circular mRNA in therapy.
Estrogen receptor-α coactivator MED1 is overexpressed in 40%-60% of human breast cancers, and its high expression is directly associated with lower disease-free survival in patients receiving anti-estrogen therapy. However, the molecular mechanism of MED1 upregulation and activation in resistance to breast cancer therapy is still unclear to researchers.
Recently, Belgian scientists published a research paper titled "Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity" in Nature Communications, a subsidiary of Nature. The study developed a Triplet lipid nanoparticles (LNP) therapy, in which intratumoral injection of LNP-delivered mRNA encoding IL-21, IL-7, and 4-1BBL can induce systemic anti-tumor immune response.
In the process of mRNA translation into protein, transfer RNA (tRNA) is responsible for recognizing each codon on the mRNA and adding the corresponding amino acid to the polypeptide chain, which is then further folded and modified into protein. Recently, Professor Joshua Mendell's team at the University of Texas Southwestern Medical Center published a research paper titled "Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes" in the international top academic journal Science. Through cryo-electron microscopy and tRNA mutation experiments, the study found that the specific tRNA that decodes the arginine codon directly recruits the CCR4-NOT complex to the translating ribosome, initiates mRNA degradation, and thus promotes mRNA turnover. In contrast, some tRNAs have structural features that prevent the recruitment of the CCR4-NOT complex.
Researchers from Georgia Institute of Technology and Emory University School of Medicine published a research paper titled "Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys" in Nature Biotechnology, a subsidiary of Nature. The study developed a lipid nanoparticle (LNP) called LNP67, which does not require bone marrow mobilization or chemotherapy pretreatment and is not modified with targeting ligands. It can deliver mRNA to hematopoietic stem/progenitor cells (HSPC) in rhesus monkeys at a dose as low as 0.25 mg/kg.
Transfer RNA halves (tRHs) have multiple biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions is currently unclear to researchers. Recently, in a research report titled "5'-tRNAGly(GCC) halves generated by IRE1α are linked to the ER stress response" published in the international journal Nature Communications, scientists from Yanbian University and other institutions in China revealed the synthesis process and key role of the transfer RNA-derived fragment 5'-tRH-GlyGCC in cancer progression. By interacting with splicing factors, it may be able to regulate gene expression, alternative splicing, and messenger RNA processing.
Neville E. Sanjana's team at New York University published a research paper titled "Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells" in the international academic journal Cell. The study developed a transcriptome-scale CRISPR screening technology based on CRISPR-Cas13 targeting RNA, and used this technology to screen and identify 778 essential lncRNAs in 5 human cells from different tissues, indicating that many lncRNAs are not junk, but play an essential and important role in human cancer and development.
In October 2024, Victor Ambros and Gary Ruvkun were awarded the Nobel Prize in Physiology or Medicine for their discovery of the central role of microRNA (miRNA) in gene expression. This discovery in 1993 revealed that miRNA regulates gene expression by binding to target mRNA and inhibiting its translation. Since then, the important role of miRNA in multiple gene expression pathways such as cell differentiation, proliferation and survival has gradually been recognized. However, although the biological functions of miRNA have been well studied, the road to applying miRNA in clinical treatment is still long and challenging.
