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Theranostics 2021The approval of the first small interfering RNA (siRNA) drug Patisiran by FDA in 2018 marks a new era of RNA interference (RNAi) therapeutics. MicroRNAs (miRNA), an... (Review)
Review
The approval of the first small interfering RNA (siRNA) drug Patisiran by FDA in 2018 marks a new era of RNA interference (RNAi) therapeutics. MicroRNAs (miRNA), an important post-transcriptional gene regulator, are also the subject of both basic research and clinical trials. Both siRNA and miRNA mimics are ~21 nucleotides RNA duplexes inducing mRNA silencing. Given the well performance of siRNA, researchers ask whether miRNA mimics are unnecessary or developed siRNA technology can pave the way for the emergence of miRNA mimic drugs. Through comprehensive comparison of siRNA and miRNA, we focus on (1) the common features and lessons learnt from the success of siRNAs; (2) the unique characteristics of miRNA that potentially offer additional therapeutic advantages and opportunities; (3) key areas of ongoing research that will contribute to clinical application of miRNA mimics. In conclusion, miRNA mimics have unique properties and advantages which cannot be fully matched by siRNA in clinical applications. MiRNAs are endogenous molecules and the gene silencing effects of miRNA mimics can be regulated or buffered to ameliorate or eliminate off-target effects. An in-depth understanding of the differences between siRNA and miRNA mimics will facilitate the development of miRNA mimic drugs.
Topics: Animals; Biomimetic Materials; Biomimetics; Gene Expression Regulation; Gene Silencing; Humans; MicroRNAs; Molecular Mimicry; RNA Interference; RNA, Small Interfering
PubMed: 34522211
DOI: 10.7150/thno.62642 -
Viruses May 2019The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In... (Review)
Review
The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely understood. Recent work suggests that antiviral RNAi is active in undifferentiated stem cells and that antiviral RNAi can be uncovered in differentiated cells in which the IFN system is inactive or in infections with viruses lacking putative viral suppressors of RNAi. In this review, we describe the mechanism of RNAi and its antiviral functions in insects and mammals. We draw parallels and highlight differences between (antiviral) RNAi in these classes of animals and discuss open questions for future research.
Topics: Animals; Antiviral Agents; Immunity, Innate; Insecta; Interferon Type I; Mammals; MicroRNAs; RNA Interference; RNA Viruses; RNA, Small Interfering; Viruses
PubMed: 31100912
DOI: 10.3390/v11050448 -
Current Opinion in Biotechnology Aug 2021Small RNA (sRNA)-mediated RNA interference (RNAi) is a regulatory mechanism conserved in almost all eukaryotes. sRNAs play a critical role in host pathogen interactions... (Review)
Review
Small RNA (sRNA)-mediated RNA interference (RNAi) is a regulatory mechanism conserved in almost all eukaryotes. sRNAs play a critical role in host pathogen interactions either endogenously or by traveling between the interacting organisms and inducing 'cross-Kingdom RNAi' in the counterparty. Cross-kingdom RNAi is the mechanistic basis of host-induced gene silencing (HIGS), which relies on genetically expressing pathogen-gene targeting RNAs in crops, and has been successfully utilized against both microbial pathogens and pests. HIGS is limited by the need to produce genetically engineered crops. Recent studies have demonstrated that double-stranded RNAs and sRNAs can be efficiently taken up by many fungal pathogens, and induce gene silencing in fungal cells. This mechanism, termed 'environmental RNAi', allows direct application of pathogen-gene targeting RNAs onto crops to silence fungal virulence-related genes for plant protection. In this review, we will focus on how we can leverage cross-kingdom RNAi and environmental RNAi for crop disease control.
Topics: Crop Protection; Crops, Agricultural; RNA Interference; RNA, Plant; RNA, Small Interfering
PubMed: 34217122
DOI: 10.1016/j.copbio.2021.06.005 -
Viruses Apr 2015Baculoviruses are widely encountered in nature and a great deal of data is available about their safety and biology. Recently, these versatile, insect-specific viruses... (Review)
Review
Baculoviruses are widely encountered in nature and a great deal of data is available about their safety and biology. Recently, these versatile, insect-specific viruses have demonstrated their usefulness in various biotechnological applications including protein production and gene transfer. Multiple in vitro and in vivo studies exist and support their use as gene delivery vehicles in vertebrate cells. Recently, baculoviruses have also demonstrated high potential in RNAi applications in which several advantages of the virus make it a promising tool for RNA gene transfer with high safety and wide tropism.
Topics: Animals; Arthropods; Baculoviridae; Gene Transfer Techniques; Genetic Vectors; RNA Interference; Transduction, Genetic; Vertebrates
PubMed: 25912715
DOI: 10.3390/v7042099 -
Journal of Biosciences 2020The two biological evidences to endorse the antiviral activity of RNA interference (RNAi) are biogenesis of viral-siRNA (v-siRNA) by the host and encoding of... (Review)
Review
The two biological evidences to endorse the antiviral activity of RNA interference (RNAi) are biogenesis of viral-siRNA (v-siRNA) by the host and encoding of RNAi-suppressor protein by viral genome. It has been recently established that mammals and mammalian cell lines mount antiviral RNAi to defend themselves against the invading viruses. The large part of viral pathogenicity is also due to the RNAi suppressor proteins. In this context it is only natural to ask what kinds of RNAi suppressors are encoded by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the central character of the present pandemic. The following mini review addresses this question.
Topics: Animals; Betacoronavirus; COVID-19; Cell Line; Chlorocebus aethiops; Coronavirus Infections; Host-Pathogen Interactions; Humans; Immunity, Innate; Pandemics; Pneumonia, Viral; RNA Interference; RNA, Small Interfering; SARS-CoV-2; Vero Cells; Viral Proteins
PubMed: 32713862
DOI: 10.1007/s12038-020-00071-0 -
Bioengineered 2015RNA interference (RNAi) in insects is a gene regulatory process that also plays a vital role in the maintenance and in the regulation of host defenses against invading... (Review)
Review
RNA interference (RNAi) in insects is a gene regulatory process that also plays a vital role in the maintenance and in the regulation of host defenses against invading viruses. Small RNAs determine the specificity of the RNAi through precise recognition of their targets. These small RNAs in insects comprise small interfering RNAs (siRNAs), micro RNAs (miRNAs) and Piwi interacting RNAs (piRNAs) of various lengths. In this review, we have explored different forms of the RNAi inducers that are presently in use, and their applications for an effective and efficient fundamental and practical RNAi research with insects. Further, we reviewed trends in next generation sequencing (NGS) technologies and their importance for insect RNAi, including the identification of novel insect targets as well as insect viruses. Here we also describe a rapidly emerging trend of using plant viruses to deliver the RNAi inducer molecules into insects for an efficient RNAi response.
Topics: Animals; Genetic Engineering; Insecta; RNA Interference; RNA, Small Interfering
PubMed: 25424593
DOI: 10.4161/21655979.2014.979701 -
American Journal of Transplantation :... Apr 2020RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest.... (Review)
Review
RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest. In 2006, the discovery of RNAi was awarded the Nobel Prize in Medicine and its success has accumulated since. Gene silencing through RNAi has been used successfully in a broad range of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Here, genes related to ischemia-reperfusion injury (IRI) or graft rejection may be silenced to improve organ quality after transplantation. Several strategies have been used to deliver siRNA, and pretransplant machine perfusion presents a unique opportunity to deliver siRNA to the target organ during ex situ preservation. In this review, the potential of RNAi in the field of organ transplantation will be discussed. A brief overview on the discovery of RNAi, its mechanism, and limitations are included. In addition, studies using RNAi to target genes related to IRI in liver, kidney, lung, and heart transplantation are discussed.
Topics: Humans; Organ Transplantation; Perfusion; RNA Interference; RNA, Small Interfering; Reperfusion Injury
PubMed: 31680428
DOI: 10.1111/ajt.15689 -
International Journal of Molecular... Aug 2021() is an opportunistic pathogen showing a high intrinsic resistance to a wide variety of antibiotics. It causes nosocomial infections that are particularly detrimental... (Review)
Review
() is an opportunistic pathogen showing a high intrinsic resistance to a wide variety of antibiotics. It causes nosocomial infections that are particularly detrimental to immunocompromised individuals and to patients suffering from cystic fibrosis. We provide a snapshot on regulatory RNAs of that impact on metabolism, pathogenicity and antibiotic susceptibility. Different experimental approaches such as in silico predictions, co-purification with the RNA chaperone Hfq as well as high-throughput RNA sequencing identified several hundreds of regulatory RNA candidates in . Notwithstanding, using in vitro and in vivo assays, the function of only a few has been revealed. Here, we focus on well-characterized small base-pairing RNAs, regulating specific target genes as well as on larger protein-binding RNAs that sequester and thereby modulate the activity of translational repressors. As the latter impact large gene networks governing metabolism, acute or chronic infections, these protein-binding RNAs in conjunction with their cognate proteins are regarded as global post-transcriptional regulators.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; RNA Interference; RNA Processing, Post-Transcriptional; RNA, Bacterial; RNA-Binding Proteins
PubMed: 34445336
DOI: 10.3390/ijms22168632 -
Nucleic Acids Research Feb 2022The rational design and realisation of simple-to-use genetic control elements that are modular, orthogonal and robust is essential to the construction of predictable and...
The rational design and realisation of simple-to-use genetic control elements that are modular, orthogonal and robust is essential to the construction of predictable and reliable biological systems of increasing complexity. To this effect, we introduce modular Artificial RNA interference (mARi), a rational, modular and extensible design framework that enables robust, portable and multiplexed post-transcriptional regulation of gene expression in Escherichia coli. The regulatory function of mARi was characterised in a range of relevant genetic contexts, demonstrating its independence from other genetic control elements and the gene of interest, and providing new insight into the design rules of RNA based regulation in E. coli, while a range of cellular contexts also demonstrated it to be independent of growth-phase and strain type. Importantly, the extensibility and orthogonality of mARi enables the simultaneous post-transcriptional regulation of multi-gene systems as both single-gene cassettes and poly-cistronic operons. To facilitate adoption, mARi was designed to be directly integrated into the modular BASIC DNA assembly framework. We anticipate that mARi-based genetic control within an extensible DNA assembly framework will facilitate metabolic engineering, layered genetic control, and advanced genetic circuit applications.
Topics: Escherichia coli; Gene Expression Regulation; Gene Regulatory Networks; Genetic Engineering; Metabolic Engineering; RNA Interference
PubMed: 35061908
DOI: 10.1093/nar/gkab1301 -
Plant Biotechnology Journal Apr 2023RNA interference (RNAi)-based technologies are starting to be commercialized as a new approach for agricultural pest control. Horizontally transferred genes (HTGs),...
RNA interference (RNAi)-based technologies are starting to be commercialized as a new approach for agricultural pest control. Horizontally transferred genes (HTGs), which have been transferred into insect genomes from viruses, bacteria, fungi or plants, are attractive targets for RNAi-mediated pest control. HTGs are often unique to a specific insect family or even genus, making it unlikely that RNAi constructs targeting such genes will have negative effects on ladybugs, lacewings and other beneficial predatory insect species. In this study, we sequenced the genome of a red, tobacco-adapted isolate of Myzus persicae (green peach aphid) and bioinformatically identified 30 HTGs. We then used plant-mediated virus-induced gene silencing (VIGS) to show that several HTGs of bacterial and plant origin are important for aphid growth and/or survival. Silencing the expression of fungal-origin HTGs did not affect aphid survivorship but decreased aphid reproduction. Importantly, although there was uptake of plant-expressed RNA by Coccinella septempunctata (seven-spotted ladybugs) via the aphids that they consumed, we did not observe negative effects on ladybugs from aphid-targeted VIGS constructs. To demonstrate that this approach is more broadly applicable, we also targeted five Bemisia tabaci (whitefly) HTGs using VIGS and demonstrated that knockdown of some of these genes affected whitefly survival. As functional HTGs have been identified in the genomes of numerous pest species, we propose that these HTGs should be explored further as efficient and safe targets for control of insect pests using plant-mediated RNA interference.
Topics: Animals; Aphids; RNA Interference; Plants, Genetically Modified; Base Sequence; Nicotiana
PubMed: 36577653
DOI: 10.1111/pbi.13992