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Immunohorizons
January 2025
Vaccine Research & Development Center, Department of Physiology & Biophysics, University of California Irvine, Irvine, CA 92697, United States.
Adjuvants play a central role in enhancing the immunogenicity of otherwise poorly immunogenic vaccine antigens. Combining adjuvants has the potential to enhance vaccine immunogenicity compared with single adjuvants, although the cellular and molecular mechanisms of combination adjuvants are not well understood. Using the influenza virus hemagglutinin H5 antigen, we define the immunological landscape of combining CpG and MPLA (TLR-9 and TLR-4 agonists, respectively) with a squalene nanoemulsion (AddaVax) using immunologic and transcriptomic profiling.
View Article and Find Full Text PDFSci Rep
January 2025
Faculty of Allied Health Sciences, Center of Excellence for Innovative Diagnosis of Antimicrobial Resistance, Chulalongkorn University, Bangkok, 10330, Thailand.
Rifampicin-resistant tuberculosis (RR-TB) is a critical issue with significant implications for patient care, public health, and TB control efforts that necessitate comprehensive strategies for detection. This study presents a novel point-of-care diagnostic tool for RR-TB detection employing a peptide nucleic acid (PNA)-paper-based sensor combined with isothermal recombinase polymerase amplification (RPA). The sensor targets mutations in codons 516, 526, and 531 of the rpoB gene, the top three common mutations associated with rifampicin-resistant strains.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Helmholtz Institute for RNA-based Infection Research, Helmholtz Centre for Infection Research (HIRI-HZI), Würzburg, Germany.
Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan.
Genomic variants causing abnormal splicing play important roles in genetic disorders and cancer development. Among them, variants that cause the formation of novel splice-sites (splice-site creating variants, SSCVs) are particularly difficult to identify and often overlooked in genomic studies. Additionally, these SSCVs are frequently considered promising candidates for treatment with splice-switching antisense oligonucleotides (ASOs).
View Article and Find Full Text PDFMolecules
December 2024
NRC Institute of Immunology FMBA of Russia, 115552 Moscow, Russia.
N-Acetylgalactosamine (GalNAc) is an efficient and multifunctional delivery tool in the development and synthesis of chemically modified oligonucleotide therapeutics (conjugates). Such therapeutics demonstrate improved potency in vivo due to the selective and efficient delivery to hepatocytes in the liver via receptor-mediated endocytosis, which is what drives the high interest in this molecule. The ways to synthesize such structures are relatively new and have not been optimized in terms of the yields and stages both in lab and large-scale synthesis.
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