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A Brief History of Genetic Therapy: Gene Therapy, Antisense Technology, and Genomics
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Altman made similar and independent observations employing the self-cleaving pre-tRNA of RNase P. Since first discovered, ribo/ymes have been identified in a variety of organisms including plant viroids and virusoids (Forster and Symons, 1987a,b); bacteria (Xu et al., 1990); the animal virus, hepatitis delta virus (Wu et al., 1989); and newt (Epstein et al., 1987).
Cascade Regulation a Model of Integrative Control of Gene Expression in Eukaryotic Cells and Organisms
Published in M. Gerald, M.D. Kolodny, Eukaryotic Gene Regulation, 2018
Another particularly interesting example for this discussion can be found in the most surprising case of the ribonuclease P which is involved in producing functional tRNA from its precursor by splicing.53 This enzyme is a true ribonucleoprotein complex including more than 75% of RNA: its sequence of 350 nucleotides is a genuine constituent, as is rRNA in ribosomes. As in the case of ribosomal RNA, this RNA might provide a double function in serving as an architectural element organizing the protein components on one hand, and on the other, may confer specificity by sequence recognition of the substrate RNA. It has been pointed out that the classical snRNAs are of a sequence complexity that might suffice for standard service functions but not for a role as discriminating regulatory agents. There exists, however, a whole battery of slightly larger nuclear RNA molecules in the molecular weight range of the RNase P RNA which is as yet hardly exploited experimentally.54 A possible generalization of the RNase P mechanism in splicing is thus conceivable and experimentally testable.
Recent Advances in Repositioning Non-Antibiotics against Tuberculosis and other Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Biological targets and/or mode of action: Phenothiazines interfere with multiple metabolic pathways that are crucial for the survival and persistence of pathogenic microorganisms (Varga et al. 2017). They show inhibitory effects on calcium-dependent enzyme systems including those catalyzing ATP hydrolysis for cellular energy. Moreover, phenothiazines have the propensity to concentrate in macrophages, an attribute that enhances their effects against phagocytosed bacteria. Inhibition of transport processes for Ca2+ or K+ enhances retention of these ions in the cytoplasm of the macrophage which promotes acidification of the phagolysosome thereby activating cidal effects (Amaral and Molnar 2014, Kristiansen et al. 2007, Martins et al. 2008). It is known that overexpression of bacterial efflux pumps confers resistance to xenobiotics including drugs which are extruded from the periplasm or cytoplasm. Phenothiazines are said to supress the activity of these transporter proteins thereby hindering bacterial drug tolerance (Amaral et al. 2004, Kaatz et al. 2003, Kristiansen et al. 2015). Recent studies have indicated that phenothiazines are inhibitors of Mtb type II NADH:menaquinone oxidoreductase, a key enzyme of the respiratory chain that is implicated in Mtb persistence in dormancy (Bald et al. 2017, Teh et al. 2007, Warman et al. 2013, Yano et al. 2006). Another study revealed that phenothiazines inhibit Mtb RNase P RNA, an endoribonuclease involved in RNA cleavage (Wu et al. 2016). Others showed that thioridazine modifies the cell envelope permeability of Mtb which has implications for drug uptake (de Keijzer et al. 2016).
The discovery and development of RNA-based therapies for treatment of HIV-1 infection
Published in Expert Opinion on Drug Discovery, 2023
Michelle J Chen, Anne Gatignol, Robert J. Scarborough
Ribozymes are RNAs that catalyze biochemical reactions. The first ribozyme was identified in self-splicing introns, where the RNA catalyzes both cleavage and ligation reactions that result in the excision of the intron from the transcript [38]. Subsequently, it was shown that RNA is the catalytic moiety in RNase P complexes that cleave pre-transfer (t)RNAs [39] and in ribosomes, where ribosomal RNA is responsible for catalyzing the linkage of amino acids to form proteins [40]. The most diverse group of ribozymes are the small, naturally occurring, self-cleaving ribozymes from which most ribozyme therapies have been derived [29,41]. Although these ribozymes catalyze self-cleavage reactions, they can be easily modified to cleave in trans and designed to target an RNA through complementary base pairing. An advantage of small self-cleaving ribozyme motifs is that they do not require cellular proteins to catalyze target cleavage, limiting their ability to disturb cellular physiology. Examples of trans-cleaving ribozymes based on these motifs are shown in Figure 1.
RT-LAMP in SARS-CoV-2 detection: point to improve primer designing and decrease molecular diagnosis pitfalls
Published in Expert Review of Molecular Diagnostics, 2022
Hossein Teimouri, Maryam Rahimi, Mahdeih Taheri, Alijan Tabarraei, Majid Shahbazi, Shahriar Omidvar, Naeme Javid, Abdolreza Fazel, Mohammad Reza Honarvar, Gholamreza Roshandel, Nafiseh Abdollahi, Ahad Yamchi, Hadi Razavi Nikoo
Viral RNA was extracted from 300 µL of aforementioned VTM by using the RNA extraction kit (Gene All, South Korea), and eluted in 100 µL of nuclease-free water. For detection of SARS-CoV-2, the specific primers and probes for E, RdRp, and N genes were used (Table 1). RT-qPCR was performed on gene E as the first-line screening tool. Positive samples (Ct< 40) were further analyzed for N gene and RdRp a duplex RT-qPCR assays using the one-step RT-qPCR kit (Sansure Biotech, China). Additionally, the RNase P gene was used as the internal control for monitoring the sample collection, sample handling, and RT-qPCR process to avoid false-negative results. A 20 µl reaction mixture contained 10 µl of RNA as the template and a 10 µl 2019-nCoV-PCR Master Mix was used for RT-qPCR reaction. Thermal cycle conditions were as follows: 30 min at 50°C, 1 cycle at 95°C for 1 min, and 45 cycles including two steps at 95°C for 15s and 60°C for the 30s. All reactions were performed in Step One Plus Real-Time PCR system (ABI, USA), and results were analyzed from three technical repeats.
Genomic and serological assessment of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in child labor
Published in Pathogens and Global Health, 2022
Niloofar Najafi, Hoorieh Soleimanjahi, Shadab Shahali, Mahmoud Reza Pourkarim, Marijn Thijssen, Fatemeh Fotouhi, Taravat Bamdad, Kayhan Azadmanesh, Zeynab Nasiri, Neda Afzali, Mohammad Reza Jabbari, Atefeh Yari, Hesam Karimi, Mohammad Hadi Karbalaei Niya
The viral RNA from nasopharyngeal and oropharyngeal specimens was extracted using the QIAamp Viral RNA Mini Kit according to the protocol that is fully automated on QIAcube. The Sansure Biotech’s Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit (PCR-Fluorescence Probing) was applied for SARS-CoV-2 genome detection with real-time RT-PCR method. The kit is designed to detect open reading frame 1ab (ORF1ab) and N gene with FAM and ROX as the reporter dye. The conditions were set in accordance with the manufacturer’s protocol. The RNase P gene is used as an internal control for monitoring the quality of sampling and avoiding false-negative results, with CY5 as a reporter dye. We also used ‘no template’ control to detect false positives caused by contamination and a positive template control for the assessment of RT-PCR performance. The following RT-PCR temperature cycles were used: 50°C for 30 min, 1 cycle; 95°C for 1 min, 1 cycle; 95°C for 15 sec, 60°C for 31 sec, 45 cycles; 25°C for 10 sec, 1 cycle according to the manufacturer protocol.