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Yakugaku Zasshi : Journal of the... 2013RNA interference (RNAi) is a potent and highly specific gene-silencing phenomenon which is initiated or triggered by double-stranded RNAs (dsRNAs). Shortly after the... (Review)
Review
RNA interference (RNAi) is a potent and highly specific gene-silencing phenomenon which is initiated or triggered by double-stranded RNAs (dsRNAs). Shortly after the development of RNAi, small interfering RNAs (siRNAs) that are 21 nucleotides in length with a 3' nucleotide overhang were shown to be very effective in mammalian cells. Much effort has been dedicated to the application of siRNAs, both as biological tools and as therapeutic agents. Currently, synthetic siRNA would be the method of choice for clinical purposes. However, natural RNA strands are quickly degraded in biological fluids. Chemically synthesized unnatural nucleotides have been developed and introduced into the siRNA strand. For example, modification of the ribose moiety with a 2'-deoxy, 2'-O-methyl, or 2'-fluoro group, or modification of the phosphate backbone have been examined. Although these modifications improve the stability of siRNA in serum, they often cause a decrease in RNAi activity. There is also concern that unnatural RNA derivatives are toxic in the human body. A method to stabilize nontoxic natural RNA strands should be very useful for applications in RNAi technology. We came up with an idea that nano-structural design stabilizes natural RNA. We tested several new designs such as dumbbell RNA, double stranded circular RNA, or branched RNA in biological stability and RNA interference activity. Consequently, dumbbell or branched design offered prolonged RNAi effect due to high biological stability.
Topics: Nanotechnology; RNA Interference
PubMed: 23449417
DOI: 10.1248/yakushi.12-00239-4 -
Nature Immunology Aug 2009By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown...
By identifying gene products whose knockdown is associated with phenotypic changes, large-scale RNA-mediated interference screens have demonstrated previously unknown components of biological pathways. This commentary provides general guidelines for using such screens to answer questions of immunological interest.
Topics: Animals; Genome-Wide Association Study; Humans; Models, Biological; RNA Interference; RNA, Small Interfering; Signal Transduction
PubMed: 19621037
DOI: 10.1038/ni0809-799 -
Journal of Insect Physiology Dec 2013RNA interference (RNAi), the sequence-specific suppression of gene expression, offers great opportunities for insect science, especially to analyze gene function, manage... (Review)
Review
RNA interference (RNAi), the sequence-specific suppression of gene expression, offers great opportunities for insect science, especially to analyze gene function, manage pest populations, and reduce disease pathogens. The accumulating body of literature on insect RNAi has revealed that the efficiency of RNAi varies between different species, the mode of RNAi delivery, and the genes being targeted. There is also variation in the duration of transcript suppression. At present, we have a limited capacity to predict the ideal experimental strategy for RNAi of a particular gene/insect because of our incomplete understanding of whether and how the RNAi signal is amplified and spread among insect cells. Consequently, development of the optimal RNAi protocols is a highly empirical process. This limitation can be relieved by systematic analysis of the molecular physiological basis of RNAi mechanisms in insects. An enhanced conceptual understanding of RNAi function in insects will facilitate the application of RNAi for dissection of gene function, and to fast-track the application of RNAi to both control pests and develop effective methods to protect beneficial insects and non-insect arthropods, particularly the honey bee (Apis mellifera) and cultured Pacific white shrimp (Litopenaeus vannamei) from viral and parasitic diseases.
Topics: Animals; Insect Control; Insecta; RNA Interference
PubMed: 24041495
DOI: 10.1016/j.jinsphys.2013.08.014 -
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 -
The Journal of Organic Chemistry Sep 2011Considerable attention has focused on the use of alternatives to the native ribose and phosphate backbone of small interfering RNAs for therapeutic applications of the... (Review)
Review
Considerable attention has focused on the use of alternatives to the native ribose and phosphate backbone of small interfering RNAs for therapeutic applications of the RNA interference pathway. In this synopsis, we highlight the less common chemical modifications, namely, those of the RNA nucleobases. Base modifications have the potential to lend insight into the mechanism of gene silencing and to lead to novel methods to overcome off-target effects that arise due to deleterious protein binding or mis-targeting of mRNA.
Topics: Gene Silencing; Molecular Probes; RNA Interference; RNA, Small Interfering
PubMed: 21834582
DOI: 10.1021/jo2012225 -
RNA Biology 2014The Argonaute family of proteins is highly evolutionarily conserved and plays essential roles in small RNA-mediated gene regulatory pathways and in a wide variety of... (Review)
Review
The Argonaute family of proteins is highly evolutionarily conserved and plays essential roles in small RNA-mediated gene regulatory pathways and in a wide variety of cellular processes. They were initially discovered by genetics studies in plants and have been well characterized as key components of gene silencing pathways guided by small RNAs, a phenomenon known as RNA interference. Conventionally, guided by different classes of small RNAs, Argonautes bind to and silence homologous target sequences at the post-transcriptional level. Increasing lines of evidence support their multi-functional roles in the nucleus. Advances in high-throughput genome-wide methodologies have greatly facilitated our understanding of their functions in post-transcriptional gene silencing as well as in other nuclear events. In this point-of-view, we will summarize key findings from genome-wide analyses of the Ago subfamily of proteins in mammals and Drosophila, discuss their nuclear functions in the regulation of transcription and alternative splicing identified in recent years, and briefly touch upon their potential implications in cancer.
Topics: Alternative Splicing; Animals; Argonaute Proteins; Cell Nucleus; Drosophila Proteins; Epigenesis, Genetic; Gene Silencing; Genome; Humans; Multigene Family; Neoplasms; RNA Interference
PubMed: 24384674
DOI: 10.4161/rna.27604 -
Wiley Interdisciplinary Reviews. RNA 2010Delivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody-mediated... (Review)
Review
Delivering polynucleotides into animals has been a major challenge facing their success as therapeutic agents. Given the matured understanding of antibody-mediated delivery techniques, it is possible to rationally design delivery vehicles that circulate in the blood stream and are specifically delivered into target organs. If the targeting moiety is designed to contain the cargo of an RNAi mediator without impacting its paratope, directed delivery can be achieved. In this article, we review the state of art in delivery technology for RNA mediators and address how this technique could soon be used to enhance the efficacy of the numerous small RNA therapeutic programs currently under evaluation.
Topics: Animals; Clinical Trials as Topic; Drug Delivery Systems; Drug Discovery; Gene Transfer Techniques; Humans; Models, Animal; RNA Interference; RNA, Small Interfering; Validation Studies as Topic
PubMed: 21935894
DOI: 10.1002/wrna.12 -
Plant Physiology Jan 2020The latest advances in the field exogenous application of RNA molecules in plants help to protect and modify them through RNA interference (RNAi).
The latest advances in the field exogenous application of RNA molecules in plants help to protect and modify them through RNA interference (RNAi).
Topics: Plants, Genetically Modified; RNA Interference; RNA, Plant; Nicotiana
PubMed: 31285292
DOI: 10.1104/pp.19.00570 -
International Journal of Biological... 2009Micro- and short-interfering RNAs represent small RNA family that are recognized as critical regulatory species across the eukaryotes. Recent high-throughput sequencing... (Review)
Review
Micro- and short-interfering RNAs represent small RNA family that are recognized as critical regulatory species across the eukaryotes. Recent high-throughput sequencing have revealed two more hidden players of the cellular small RNA pool. Reported in mammals and Caenorhabditis elegans respectively, these new small RNAs are named piwi-interacting RNAs (piRNAs) and 21U-RNAs. Moreover, small RNAs including miRNAs have been identified in unicellular alga Chlamydomonas reinhardtii, redefining the earlier concept of multi-cellularity restricted presence of these molecules. The discovery of these species of small RNAs has allowed us to understand better the usage of genome and the number of genes present but also have complicated the situation in terms of biochemical attributes and functional genesis of these molecules. Nonetheless, these new pools of knowledge have opened up avenues for unraveling the finer details of the small RNA mediated pathways.
Topics: Animals; Caenorhabditis elegans; Chlamydomonas reinhardtii; MicroRNAs; Models, Biological; RNA Interference; RNA, Small Interfering
PubMed: 19173032
DOI: 10.7150/ijbs.5.97 -
Cold Spring Harbor Symposia on... 2016Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic... (Review)
Review
Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits. Functional genomics represents a powerful approach for the identification of vulnerabilities linked to specific genetic alterations and has provided substantial insights into cancer signaling networks. Still, as inhibition of gene function can have diverse effects on both tumor and normal tissues, information on the potency of target inhibition on tumor growth as well as the toxic side effects of target inhibition are also needed. Here, we discuss our RNA interference (RNAi) pipeline for cancer target discovery based on our optimized short-hairpin RNA (shRNA) tools for negative selection screens and inducible RNAi platform that, in combination with embryonic stem cell (ESC)-based genetically engineered mouse models (GEMMs), enable deep in vivo target validation.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Embryonic Stem Cells; Humans; RNA Interference; RNA, Small Interfering; Signal Transduction
PubMed: 28057848
DOI: 10.1101/sqb.2016.81.031096