The development and improvement of ribonucleic acid therapy strategies.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhao Y
PROVIDER: S-EPMC8437697 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), remaining a global health crisis since its outbreak until now. Advanced biotechnology and research findings have revealed many suitable viral and host targets for a wide range of therapeutic strategies. The emerging ribonucleic acid therapy can modulate gene expression by post-transcriptional gene silencing (PTGS) based on Watson-Crick base pairing. RNA therapies, including antisense oligonucleotides (ASO), ribozymes, RNA interference (RNAi), aptamers, etc., were used to treat SARS-CoV whose genome is similar to SARV-CoV-2, and the past experience also applies for the treatment of COVID-19. Several studies against SARS-CoV-2 based on RNA therapeutic strategy have been reported, and a dozen of relevant preclinical or clinical trials are in process globally. RNA therapy has been a very active and important part of COVID-19 treatment. In this review, we focus on the progress of ribonucleic acid therapeutic strategies development and application, discuss corresponding problems and challenges, and suggest new strategies and solutions.
| S-EPMC9379410 | biostudies-literature
Project description:Noncoding RNA (ncRNA) is a kind of RNA that plays an important role in many biological processes, diseases, and cancers, while cannot translate into proteins. With the development of next-generation sequence technology, thousands of novel RNAs with long open reading frames (ORFs, longest ORF length > 303 nt) and short ORFs (longest ORF length ? 303 nt) have been discovered in a short time. How to identify ncRNAs more precisely from novel unannotated RNAs is an important step for RNA functional analysis, RNA regulation, etc. However, most previous methods only utilize the information of sequence features. Meanwhile, most of them have focused on long-ORF RNA sequences, but not adapted to short-ORF RNA sequences. In this paper, we propose a new reliable method called NCResNet. NCResNet employs 57 hybrid features of four categories as inputs, including sequence, protein, RNA structure, and RNA physicochemical properties, and introduces feature enhancement and deep feature learning policies in a neural net model to adapt to this problem. The experiments on benchmark datasets of 8 species shows NCResNet has higher accuracy and higher Matthews correlation coefficient (MCC) compared with other state-of-the-art methods. Particularly, on four short-ORF RNA sequence datasets, specifically mouse, Saccharomyces cerevisiae, zebrafish, and cow, NCResNet achieves greater than 10 and 15% improvements over other state-of-the-art methods in terms of accuracy and MCC. Meanwhile, for long-ORF RNA sequence datasets, NCResNet also has better accuracy and MCC than other state-of-the-art methods on most test datasets. Codes and data are available at https://github.com/abcair/NCResNet.
| S-EPMC7059790 | biostudies-literature
Project description:Betulinic acid (BA) is a lupane-type triterpene which has been considered as a promising agent to cure melanoma with no side effects. Considering that BA is naturally produced in small quantities in plants, we previously reported the success in engineering its production in yeast. In the present study, we attempted to improve BA biosynthesis in yeast by the use of different strategies.We first isolated a gene encoding a lupeol C-28 oxidase (LO) from Betula platyphylla (designated as BPLO). BPLO showed a higher activity in BA biosynthesis compared to the previously reported LOs. In addition, two yeast platforms were compared for engineering the production of BA, which demonstrated that the WAT11 strain was better to host BA pathway than the CEN.PK strain. Based on the WAT11-chassiss, the Gal80p mutant was further constructed. The mutant produced 0.16 mg/L/OD600 of BA, which was 2.2 fold of that produced by the wild type strain (0.07 mg/L/OD600).This study reported our efforts to improve BA production in yeast employing multiple strategies, which included the identification of a novel LO enzyme with a higher activity in BA biosynthesis, the evaluation of two yeast strains for hosting the BA pathway, and the up-regulation of the expression of the BA pathway genes by managing yeast GAL gene regulon circuit.
| S-EPMC4989488 | biostudies-literature
Project description:Bacterial transcriptomics is widely used to investigate gene regulation, bacterial susceptibility to antibiotics, host-pathogen interactions, and pathogenesis. Transcriptomics is crucially dependent on suitable methods to isolate and detect bacterial RNA. Microfluidics offer ways of creating integrated point-of-care systems, analysing a sample from preparation, and RNA isolation to detection. A critical requirement for on-chip diagnostics to deliver on their promise is that mRNA expression is not altered via microfluidic sample processing. This article investigates the impact of the use of microfluidics upon RNA expression of bacteria isolated from blood, a key step towards proving the suitability of such systems for further development.
| S-EPMC4449352 | biostudies-literature
Project description:BackgroundVirus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines as well as the early identification of individuals with the highest risk that may require supportive treatment.MethodsWe completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, severe acute respiratory syndrome-coronavirus, and West Nile virus.ResultsThe CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality after infection and strains exhibiting no mortality. We then used comprehensive preinfection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection.ConclusionsThese data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.
| S-EPMC7107456 | biostudies-literature
Project description:Research that is integral into a 'learning healthcare system' can promote cost effective services and knowledge creation. As such, research is defined as a 'core function' in UK health service organisations, and is often planned through research and development (R&D) strategies that aim to promote research activity and research capacity development (RCD). The discussion focuses around the content of ten R&D strategies for healthcare organisations in England and Scotland, with respect to RCD. These organisations were engaged with a research interest network called ACORN (Addressing Organisational Capacity to do Research Network) that included two Scottish Health Boards, four community and mental health trusts, two provincial district hospitals, and two teaching hospitals. We undertook a thematic documentary analysis of the R&D strategies which identified 11 'core activities' of RCD. The potential for building research capacity in these 'core activities' was established by reviewing them through the lens of a RCD framework. Core activities aimed to 'hard wire' RCD into health organisations. They demonstrated a complex interplay between developing a strong internal organisational infrastructure, and supporting individual career planning and skills development, in turn enabled by organisational processes. They also included activities to build stronger inter-organisational relationships and networks. Practitioner, manager and patient involvement was a cross cutting theme. The potential to demonstrate progress was included in plans through monitoring activity across all RCD principles. Strategies were primarily aimed at research production rather than research use. Developing 'actionable dissemination' was poorly addressed in the strategies, and represents an area for improvement. We describe strengths of RCD planning activities, and opportunities for improvement. We explore how national policy and research funders can influence health systems' engagement in research.
| S-EPMC5865402 | biostudies-literature
Project description:Objective: To develop a reliable, reproducible, and sensitive method for investigating gene-expression profiles from individual human oocytes. Setting: University medical center and university microarray laboratory. Patient(s): Couples undergoing intracytoplasmic sperm injection treatment were asked to donate their immature oocytes for research, and written informed consent was obtained in all cases. Seventy-nine human oocytes were used in total. Intervention(s): None. Main Outcome Measure(s): Amplification efficiency and microarray profiles. Result(s): Two of the five protocols (WT-Ovation One-Direct and Arcturus RiboAMp HS Plus) resulted in sufficient yields and high success rates and were further validated for their performance in obtaining reliable, reproducible, and sensitive expression profiles from individual human oocytes. Evaluation of these two protocols demonstrated that they both displayed low technical variation and produced highly reproducible profiles (r R 0.95). One of them identified significantly more transcripts but also had a higher number of false discoveries. Conclusion(s): Two protocols generated ample amounts of mRNA for (quantitative) polymerase chain reaction, microarray, and sequencing techniques. Further validation using a design that discriminates between biological and technical variation showed that both protocols can be used for gene-expression profiling of individual human oocytes.
2015-12-31 | GSE48141 | GEO
Project description:The purpose of this study was to determine the role of the proinflammatory cytokine interleukin (IL) 6 in cold-induced hypertension. Four groups of male Sprague-Dawley rats were used (6 rats per group). After blood pressure was stabilized, 3 groups received intravenous delivery of adenoassociated virus carrying IL-6 small hairpin RNA (shRNA), adenoassociated virus carrying scrambled shRNA, and PBS, respectively, before exposure to a cold environment (5 degrees C). The last group received PBS and was kept at room temperature (25 degrees C, warm) as a control. Adenoassociated virus delivery of IL-6 shRNA significantly attenuated cold-induced elevation of systolic blood pressure and kept it at the control level for < or =7 weeks (length of the study). Chronic exposure to cold upregulated IL-6 expression in aorta, heart, and kidneys and increased macrophage and T-cell infiltration in kidneys, suggesting that cold exposure increases inflammation. IL-6 shRNA delivery abolished the cold-induced upregulation of IL-6, indicating effective silence of IL-6. Interestingly, RNA interference knockdown of IL-6 prevented cold-induced inflammation, as evidenced by a complete inhibition of tumor necrosis factor-alpha expression and leukocyte infiltration by IL-6 shRNA. RNA interference knockdown of IL-6 significantly decreased the cold-induced increase in vascular superoxide production. It is noted that IL-6 shRNA abolished the cold-induced increase in collagen deposition in the heart, suggesting that inflammation is involved in cold-induced cardiac remodeling. Cold exposure caused glomerular collapses, which could be prevented by knockdown of IL-6, suggesting an important role of inflammation in cold-induced renal damage. In conclusion, cold exposure increased IL-6 expression and inflammation, which play critical roles in the pathogenesis of cold-induced hypertension and cardiac and renal damage.
| S-EPMC2894564 | biostudies-literature
Project description:We sought to identify a novel gene for dilated cardiomyopathy (DCM).DCM is a heritable, genetically heterogeneous disorder that remains idiopathic in the majority of patients. Familial cases provide an opportunity to discover unsuspected molecular bases of DCM, enabling pre-clinical risk detection.Two large families with autosomal-dominant DCM were studied. Genome-wide linkage analysis was used to identify a disease locus, followed by fine mapping and positional candidate gene sequencing. Mutation scanning was then performed in 278 unrelated subjects with idiopathic DCM, prospectively identified at the Mayo Clinic.Overlapping loci for DCM were independently mapped to chromosome 10q25-q26. Deoxyribonucleic acid sequencing of affected individuals in each family revealed distinct heterozygous missense mutations in exon 9 of RBM20, encoding ribonucleic acid (RNA) binding motif protein 20. Comprehensive coding sequence analyses identified missense mutations clustered within this same exon in 6 additional DCM families. Mutations segregated with DCM (peak composite logarithm of the odds score >11.49), were absent in 480 control samples, and altered residues within a highly conserved arginine/serine (RS)-rich region. Expression of RBM20 messenger RNA was confirmed in human heart tissue.Our findings establish RBM20 as a DCM gene and reveal a mutation hotspot in the RS domain. RBM20 is preferentially expressed in the heart and encodes motifs prototypical of spliceosome proteins that regulate alternative pre-messenger RNA splicing, thus implicating a functionally distinct gene in human cardiomyopathy. RBM20 mutations are associated with young age at diagnosis, end-stage heart failure, and high mortality.
| S-EPMC2782634 | biostudies-literature
Project description:Succinate dehydrogenase (SDH) complex connects both the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) in the mitochondria. However, SDH mutation or dysfunction-induced succinate accumulation results in multiple cancers and non-cancer diseases. The mechanistic studies show that succinate activates hypoxia response and other signal pathways via binding to 2-oxoglutarate-dependent oxygenases and succinate receptors. Recently, the increasing knowledge of ribonucleic acid (RNA) networks, including non-coding RNAs, RNA editors, and RNA modifiers has expanded our understanding of the interplay between SDH and RNA networks in cancer and other diseases. Here, we summarize recent discoveries in the RNA networks and their connections to SDH. Additionally, we discuss current therapeutics targeting SDH in both pre-clinical and clinical trials. Thus, we propose a new model of SDH-RNA network interaction and bring promising RNA therapeutics against SDH-relevant cancer and other diseases.
| S-EPMC7693138 | biostudies-literature