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BMB Reports Jun 2023RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face... (Review)
Review
RNAs are pivotal molecules acting as messengers of genetic information and regulatory molecules for cellular development and survival. From birth to death, RNAs face constant cellular decision for the precise control of cellular function and activity. Most eukaryotic cells employ conserved machineries for RNA decay including RNA silencing and RNA quality control (RQC). In plants, RQC monitors endogenous RNAs and degrades aberrant and dysfunctional species, whereas RNA silencing promotes RNA degradation to repress the expression of selected endogenous RNAs or exogenous RNA derived from transgenes and virus. Interestingly, emerging evidences have indicated that RQC and RNA silencing interact with each by sharing target RNAs and regulatory components. Such interaction should be tightly organized for proper cellular survival. However, it is still elusive that how each machinery specifically recognizes target RNAs. In this review, we summarize recent advances on RNA silencing and RQC pathway and discuss potential mechanisms underlying the interaction between the two machineries. [BMB Reports 2023; 56(6): 321-325].
Topics: RNA Interference; RNA, Small Interfering; Plants; RNA Stability; Quality Control
PubMed: 37156633
DOI: 10.5483/BMBRep.2023-0049 -
Viruses Aug 2020RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA)... (Review)
Review
RNA interference (RNAi) provides the means for alternative antiviral therapy. Delivery of RNAi in the form of short interfering RNA (siRNA), short hairpin RNA (shRNA) and micro-RNA (miRNA) have demonstrated efficacy in gene silencing for therapeutic applications against viral diseases. Bioinformatics has played an important role in the design of efficient RNAi sequences targeting various pathogenic viruses. However, stability and delivery of RNAi molecules have presented serious obstacles for reaching therapeutic efficacy. For this reason, RNA modifications and formulation of nanoparticles have proven useful for non-viral delivery of RNAi molecules. On the other hand, utilization of viral vectors and particularly self-replicating RNA virus vectors can be considered as an attractive alternative. In this review, examples of antiviral therapy applying RNAi-based approaches in various animal models will be described. Due to the current coronavirus pandemic, a special emphasis will be dedicated to targeting Coronavirus Disease-19 (COVID-19).
Topics: Animals; Antiviral Agents; COVID-19; Computational Biology; Coronavirus Infections; Gene Silencing; Humans; Immunocompromised Host; Pandemics; Pneumonia, Viral; RNA Interference
PubMed: 32842491
DOI: 10.3390/v12090924 -
International Journal of Molecular... Aug 2023Our duty to conserve global natural ecosystems is increasingly in conflict with our need to feed an expanding population. The use of conventional pesticides not only... (Review)
Review
Our duty to conserve global natural ecosystems is increasingly in conflict with our need to feed an expanding population. The use of conventional pesticides not only damages the environment and vulnerable biodiversity but can also still fail to prevent crop losses of 20-40% due to pests and pathogens. There is a growing call for more ecologically sustainable pathogen control measures. RNA-based biopesticides offer an eco-friendly alternative to the use of conventional fungicides for crop protection. The genetic modification (GM) of crops remains controversial in many countries, though expression of transgenes inducing pathogen-specific RNA interference (RNAi) has been proven effective against many agronomically important fungal pathogens. The topical application of pathogen-specific RNAi-inducing sprays is a more responsive, GM-free approach to conventional RNAi transgene-based crop protection. The specific targeting of essential pathogen genes, the development of RNAi-nanoparticle carrier spray formulations, and the possible structural modifications to the RNA molecules themselves are crucial to the success of this novel technology. Here, we outline the current understanding of gene silencing pathways in plants and fungi and summarize the pioneering and recent work exploring RNA-based biopesticides for crop protection against fungal pathogens, with a focus on spray-induced gene silencing (SIGS). Further, we discuss factors that could affect the success of RNA-based control strategies, including RNA uptake, stability, amplification, and movement within and between the plant host and pathogen, as well as the cost and design of RNA pesticides.
Topics: Biological Control Agents; Ecosystem; RNA Interference; RNA, Small Interfering; Crops, Agricultural; Pesticides; Plant Diseases
PubMed: 37569766
DOI: 10.3390/ijms241512391 -
BioTechniques Dec 2020Plant diseases caused by a variety of pathogens can have severe effects on crop plants and even plants in natural ecosystems. Despite many effective conventional... (Review)
Review
Plant diseases caused by a variety of pathogens can have severe effects on crop plants and even plants in natural ecosystems. Despite many effective conventional approaches to control plant diseases, new, efficacious, environmentally sound and cost-effective approaches are needed, particularly with our increasing human population and the effects on crop production and plant health caused by climate change. RNA interference (RNAi) is a gene regulation and antiviral response mechanism in eukaryotes; transgenic and non transgenic plant-based RNAi approaches have shown great effectiveness and potential to target specific plant pathogens and help control plant diseases, especially when no alternatives are available. Here we discuss ways in which RNAi has been used against different plant pathogens, and some new potential applications for plant disease control.
Topics: MicroRNAs; Models, Biological; Plant Diseases; Plants, Genetically Modified; RNA Interference; RNA, Small Interfering
PubMed: 33070628
DOI: 10.2144/btn-2020-0098 -
STAR Protocols Mar 2021Whole planarian chromosome squash allows researchers to qualitatively analyze chromosome integrity. Treatment with colchicine is used to halt dividing cells within...
Whole planarian chromosome squash allows researchers to qualitatively analyze chromosome integrity. Treatment with colchicine is used to halt dividing cells within metaphase and does not require amputation or tissue puncturing. In combination with acetic-orcein, a stain-fixative for chromosomes, this strategy is suitable for animals with friable tissues caused by drug treatment, radiation, and RNA interference phenotypes. The whole planarian squash method presented here is a minimally invasive procedure that facilitates simultaneous analysis of chromosomal integrity in control and experimental animals. For complete details on the use and execution of this protocol, please refer to Peiris et al. (2016).
Topics: Animals; Chromosomes; Metaphase; Planarians; RNA Interference
PubMed: 33490976
DOI: 10.1016/j.xpro.2020.100257 -
Current Neuropharmacology 2021Neurodegenerative diseases (ND), as a group of central nervous system (CNS) disorders, are among the most prominent medical problems of the 21st century. They are often... (Review)
Review
Neurodegenerative diseases (ND), as a group of central nervous system (CNS) disorders, are among the most prominent medical problems of the 21st century. They are often associated with considerable disability, motor dysfunction and dementia and are more common in the aged population. ND imposes a psychologic, economic and social burden on the patients and their families. Currently, there is no effective treatment for ND. Since many ND result from the gain of function of a mutant allele, small interference RNA (siRNA) can be a potential therapeutic agent for ND management. Based on the RNA interference (RNAi) approach, siRNA is a powerful tool for modulating gene expression through gene silencing. However, there are some obstacles in the clinical application of siRNA, including unfavorable immune response, off-target effects, instability of naked siRNA, nuclease susceptibility and a need to develop a suitable delivery system. Since there are some issues related to siRNA delivery routes, in this review, we focus on the application of siRNA in the management of ND treatment from 2000 to 2020.
Topics: Aged; Gene Silencing; Humans; Neoplasms; Neurodegenerative Diseases; RNA Interference; RNA, Small Interfering
PubMed: 33797386
DOI: 10.2174/1570159X19666210402104054 -
The New Phytologist Jul 2021Host-induced gene silencing (HIGS) technology has emerged as a powerful alternative to chemical treatments for protecting plants from pathogens or pests. More than 170... (Review)
Review
Host-induced gene silencing (HIGS) technology has emerged as a powerful alternative to chemical treatments for protecting plants from pathogens or pests. More than 170 HIGS studies have been published so far, and HIGS products have been launched. First, we discuss the strengths and limitations of this technology in a pathosystem-specific context. Next, we highlight the requirement for fundamental knowledge on the molecular mechanisms (i.e. uptake, processing and translocation of transgene-expressed double-stranded RNAs) that determine the efficacy and specificity of HIGS. Additionally, we speculate on the contribution of host and target RNA interference machineries, which may be incompatible depending on the lifestyle of the pathogen or pest. Finally, we predict that closing these gaps in knowledge will lead to the development of novel integrative concepts, precise risk assessment and tailor-made HIGS therapy for plant diseases.
Topics: Gene Silencing; Plant Diseases; Plants; RNA Interference; RNA, Double-Stranded
PubMed: 33774815
DOI: 10.1111/nph.17364 -
Journal of Controlled Release :... Nov 2022RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA)... (Review)
Review
RNA interference (RNAi) is a major cellular mechanism regulating gene expression in which short double-stranded RNA molecules called small interfering RNA (siRNA) mediate sequence-specific mRNA degradation. RNAi technology has recently emerged as a promising therapeutic platform for the effective treatment of various diseases caused by inappropriate gene activity, such as cancer. However, the clinical translation of siRNA therapeutics has been hampered by the major hurdles associated with biological instability and limited delivery efficiency. Based on the various efforts, recent siRNA delivery strategies using cationic lipids and polymers allowed to enhance pharmacokinetics and delivery efficiency, resulting in potent and liver-targeted RNAi therapy. However, non-specific protein adsorption, high liver accumulation, and severe toxicity of cationic nanocarriers still limit the possibility of transfer of siRNA therapeutics from the laboratory to the clinic. One of the promising delivery strategies to overcome the limitations of siRNA therapeutics is carrier-free bioconjugation which is chemically modified and connected with biocompatible molecules such as lipids, peptides, antibodies, aptamers, and polymers. These molecularly engineered siRNA conjugates can be utilized for RNAi delivery to tissues beyond the liver, providing opportunities for clinical translation. This review focused on introducing the recent progress in molecularly engineered siRNA conjugates and their applications toward overcoming the limitations of siRNA for tumor-targeted delivery and therapy.
Topics: Humans; RNA, Small Interfering; RNAi Therapeutics; RNA, Double-Stranded; RNA Interference; Neoplasms; Polymers; Lipids
PubMed: 36152808
DOI: 10.1016/j.jconrel.2022.09.040 -
Advanced Drug Delivery Reviews Jul 2021Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive... (Review)
Review
Ribonucleic acid interference (RNAi) is an innovative treatment strategy for a myriad of indications. Non-viral synthetic nanoparticles (NPs) have drawn extensive attention as vectors for RNAi due to their potential advantages, including improved safety, high delivery efficiency and economic feasibility. However, the complex natural process of RNAi and the susceptible nature of oligonucleotides render the NPs subject to particular design principles and requirements for practical fabrication. Here, we summarize the requirements and obstacles for fabricating non-viral nano-vectors for efficient RNAi. To address the delivery challenges, we discuss practical guidelines for materials selection and NP synthesis in order to maximize RNA encapsulation efficiency and protection against degradation, and to facilitate the cytosolic release of oligonucleotides. The current status of clinical translation of RNAi-based therapies and further perspectives for reducing the potential side effects are also reviewed.
Topics: Animals; Gene Transfer Techniques; Humans; Nanoparticles; Oligonucleotides; RNA Interference; RNA, Small Interfering
PubMed: 34019958
DOI: 10.1016/j.addr.2021.05.018 -
Current Opinion in Plant Biology Dec 2023Spray-induced gene silencing (SIGS) is a powerful and eco-friendly method for crop protection. Based off the discovery of RNA uptake ability in many fungal pathogens,... (Review)
Review
Spray-induced gene silencing (SIGS) is a powerful and eco-friendly method for crop protection. Based off the discovery of RNA uptake ability in many fungal pathogens, the application of exogenous RNAs targeting pathogen/pest genes results in gene silencing and infection inhibition. However, SIGS remains hindered by the rapid degradation of RNA in the environment. As extracellular vesicles are used by plants, animals, and microbes in nature to transport RNAs for cross-kingdom/species RNA interference between hosts and microbes/pests, nanovesicles and other nanoparticles have been used to prevent RNA degradation. Efforts examining the effect of nanoparticles on RNA stability and internalization have identified key attributes that can inform better nanocarrier designs for SIGS. Understanding sRNA biogenesis, cross-kingdom/species RNAi, and how plants and pathogens/pests naturally interact are paramount for the design of SIGS strategies. Here, we focus on nanotechnology advancements for the engineering of innovative RNA-based disease control strategies against eukaryotic pathogens and pests.
Topics: Animals; RNA, Small Interfering; Crop Protection; RNA Interference; Gene Silencing; Plants
PubMed: 37696727
DOI: 10.1016/j.pbi.2023.102441