Riboswitches are an attractive target for the directed design of RNA-based regulators by in silico prediction. These noncoding RNA elements consist of an aptamer platform for the highly selective ligand recognition and an expression platform which controls gene activity typically at the level of transcription or translation. In previous work, we could successfully apply RNA folding prediction to implement a new riboswitch mechanism regulating processing of a tRNA by RNase P. In this contribution, we present detailed information about our pipeline consisting of in silico design combined with the biochemical analysis for the verification of the implemented mechanism. Furthermore, we discuss the applicability of the presented biochemical in vivo and in vitro methods for the characterization of other artificial riboswitches.
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http://dx.doi.org/10.1007/978-1-0716-2421-0_11 | DOI Listing |
Spectrochim Acta A Mol Biomol Spectrosc
January 2025
CICS-UBI - Health Sciences Research Centre University of Beira Interior Covilhã Portugal; RISE-Health, Departamento de Química, Faculdade de Ciências, Universidade da Beira Interior, Rua Marquês d'Ávila e Bolama 6201-001 Covilhã, Portugal; Departamento de Química, Universidade da Beira Interior, Rua Marquês de Ávila e Bolama 6201-001 Covilhã, Portugal. Electronic address:
Rapid, quantitative, and sensitive detection of viral oligonucleotides can help to diagnose the infection before symptoms occur, monitor disease progression, and identify viral subtypes. A one-pot, simple, rapid hairpin-mediated nicking enzymatic signal amplification (HNESA) method was previously developed for nucleic acids detection. In the present work, this method was applied for the detection of SARS-CoV-2 RNA by designing an assistant probe (AP) that contains the complementary sequence for the target, the sequence of hybridization with the loop region of the molecular beacon (MB), and the recognition site of the nicking endonuclease Nt.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754 Egypt. Electronic address:
Anti-infective agents are a class of drugs used to prevent, treat, or control infections caused by microorganisms such as bacteria, viruses, fungi, and parasites. They play a crucial role in modern medicine, helping to reduce the severity of infections and, in many cases, save lives. This study aims at the design and synthesis of hybrid compounds containing quinoxaline, pyrrolidine, and an azo bridge to combat antimicrobial resistance, and evaluating their antimicrobial, antifungal, and antiviral activities against various pathogenic strains.
View Article and Find Full Text PDFClin Cancer Res
January 2025
ACTREC, Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
Purpose: Identifying therapeutic targets for Signet Ring Cell Carcinoma (SRCC) of the colon and rectum is a clinical challenge due to the lack of Patient-Derived Organoids (PDO) or Xenografts (PDX). We present a robust method to establish PDO and PDX models to answer address this unmet need. We demonstrate that these models identify novel therapeutic strategies targeting therapy resistance and peritoneal metastasis.
View Article and Find Full Text PDFSci Transl Med
January 2025
Graduate Program in Human Genetics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue (M-860), Miami, FL 33136, USA.
Primary mitochondrial disorders are most often caused by deleterious mutations in the mitochondrial DNA (mtDNA). Here, we used a mitochondrial DddA-derived cytosine base editor (DdCBE) to introduce a compensatory edit in a mouse model that carries the pathological mutation in the mitochondrial transfer RNA (tRNA) alanine (mt-tRNA) gene. Because the original m.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
University of Science and Technology of China School of Biomedical Engineering, Department of Polymer Science and Engineering, 96 Jinzhai Road, 230026, Hefei, CHINA.
Lipid nanoparticles (LNPs) based messenger RNA (mRNA) therapeutics hold immense promise for treating a wide array of diseases, while their nonhepatic organs targeting and insufficient endosomal escape efficiency remain challenges. For LNPs, polyethylene glycol (PEG) lipids have a crucial role in stabilizing them in aqueous medium, but they severely hinder cellular uptake and reduce transfection efficiency. In this study, we designed ultrasound (US)-assisted fluorinated PEGylated LNPs (F-LNPs) to enhance spleen-targeted mRNA delivery and transfection.
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