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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 -
The New England Journal of Medicine Oct 2023
Topics: Humans; RNA Interference; Hypertension
PubMed: 37819965
DOI: 10.1056/NEJMc2310167 -
Advanced Drug Delivery Reviews Oct 2023Small interfering RNAs (siRNAs) are among the most promising therapeutic platforms in many life-threatening diseases. Owing to the significant advances in siRNA design,... (Review)
Review
Small interfering RNAs (siRNAs) are among the most promising therapeutic platforms in many life-threatening diseases. Owing to the significant advances in siRNA design, many challenges in the stability, specificity and delivery of siRNA have been addressed. However, safety concerns and dose-limiting toxicities still stand among the reasons for the failure of clinical trials of potent siRNA therapies, calling for a need of more comprehensive understanding of their potential mechanisms of toxicity. This review delves into the intrinsic and delivery related toxicity mechanisms of siRNA drugs and takes a holistic look at the safety failure of the clinical trials to identify the underlying causes of toxicity. In the end, the current challenges, and potential solutions for the safety assessment and high throughput screening of investigational siRNA and delivery systems as well as considerations for design strategies of safer siRNA therapeutics are outlined.
Topics: Humans; RNA, Small Interfering; High-Throughput Screening Assays; RNA Interference
PubMed: 37567502
DOI: 10.1016/j.addr.2023.115052 -
Methods in Molecular Biology (Clifton,... 2022Xenacoelomorpha are a phylogenetically and biologically interesting, but severely understudied group of worm-like animals. Among them, the acoel Isodiametra pulchra has...
Xenacoelomorpha are a phylogenetically and biologically interesting, but severely understudied group of worm-like animals. Among them, the acoel Isodiametra pulchra has been shown to be amenable to experimental work, including the study of stem cells and regeneration. The animal is capable of regenerating the posterior part of the body, but not its head. Here, methods such as nucleic acid extractions, in situ hybridisation, RNA interference, antibody and cytochemical stainings, and the general handling of the animals are presented.
Topics: Animals; In Situ Hybridization; RNA Interference; Stem Cells
PubMed: 35359312
DOI: 10.1007/978-1-0716-2172-1_13 -
Virologie (Montrouge, France) Dec 2020A key aspect of antiviral immunity is the distinction between "self" and "non-self" components. This distinction can be established through the detection of... (Review)
Review
A key aspect of antiviral immunity is the distinction between "self" and "non-self" components. This distinction can be established through the detection of double-stranded RNA (dsRNA), a common sign of viral infection, by cytosolic RNA helicases. Depending on the organism, two major antiviral pathways can be induced by dsRNA helicases: RNA interference (RNAi) and interferon (IFN) signaling. In the RNAi pathway, dsRNAs are recognized by a Dicer protein, and are then used for the sequence-dependent recognition and subsequent degradation of the complementary viral RNAs. In the IFN signaling pathway, dsRNAs are recognized by a RIG-like receptor (RLR), which induces a signaling cascade in order to induce the expression of IFNs, cytokines and chemokines. In this review, we discuss the RNA features that can be used by the cell to detect a viral infection, the two aforementioned types of helicase-mediated sensing, as well as some viral escape mechanisms developed to avoid recognition.
Topics: Humans; Interferons; RNA Interference; RNA, Double-Stranded; Signal Transduction; Virus Diseases
PubMed: 33441291
DOI: 10.1684/vir.2020.0871 -
Nephrology, Dialysis, Transplantation :... May 2023RNA interference (RNAi) occurs in all organisms and modulates most, if not all, biological pathways. It is the process by which non-coding RNAs, including microRNAs... (Review)
Review
RNA interference (RNAi) occurs in all organisms and modulates most, if not all, biological pathways. It is the process by which non-coding RNAs, including microRNAs (miRNAs), regulate gene transcription and post-transcriptional processing of messenger RNA (mRNA). A single miRNA can modulate several genes within a cell, and several miRNAs can regulate expression of the same gene, adding tiers of complexity to the regulation of gene expression. miRNAs and other RNAi approaches have been successfully used in vitro and in vivo to selectively manipulate gene transcription, making them pivotal agents for basic science research and candidates for targeted therapeutics. This review focuses on miRNAs and their potential as biomarkers and novel therapeutics for glomerular disease.
Topics: Humans; MicroRNAs; RNA Interference
PubMed: 35906877
DOI: 10.1093/ndt/gfac230 -
Journal of Agricultural and Food... Apr 2021For decades, the tight regulatory functions of DNA and RNA have been the focus of extensive research with the goal of harnessing RNA molecules (e.g., microRNA and small... (Review)
Review
For decades, the tight regulatory functions of DNA and RNA have been the focus of extensive research with the goal of harnessing RNA molecules (e.g., microRNA and small interfering RNA) to control gene expression and to study biological functions. RNA interference (RNAi) has shown evidence of mediating gene expression, has been utilized to study functional genomics, and recently has potential in therapeutic agents. RNAi is a natural mechanism and a well-studied tool that can be used to silence specific genes. This method is also used in aquaculture as a research tool and to enhance immune responses. RNAi methods do have their limitations (e.g., immune triggering); efficient and easy-to-use RNAi methods for large-scale applications need further development. Despite these limitations, RNAi methods have been successfully used in aquaculture, in particular shrimp. This review discusses the uses of RNAi in aquaculture, such as immune- and production-related issues and the possible limitations that may hinder the application of RNAi in the aquaculture industry. Our challenge is to develop a highly potent RNAi delivery platform that could complete the desired action with minimal side effects and which can be applied on a large-scale with relatively little expense in the aquaculture industry.
Topics: Animals; Aquaculture; MicroRNAs; RNA Interference; RNA, Double-Stranded; RNA, Small Interfering
PubMed: 33835783
DOI: 10.1021/acs.jafc.1c00268 -
Translational Research : the Journal of... Dec 2019RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy... (Review)
Review
RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. One of the main challenges to clinical translation is the lack of a suitable delivery vehicle to efficiently and safely access diverse pathologies. Moreover, the ideal targets in treatment of arthritides remain elusive given the complexity and heterogeneity of these disease pathogeneses. Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
Topics: Animals; Arthritis; Cell Engineering; Gene Transfer Techniques; Humans; Inflammation; RNA Interference; Signal Transduction
PubMed: 31351032
DOI: 10.1016/j.trsl.2019.07.002 -
Stem Cells Translational Medicine Aug 2023The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in... (Review)
Review
The progressive appreciation that multiple types of RNAs regulate virtually all aspects of tissue function and the availability of effective tools to deliver RNAs in vivo now offers unprecedented possibilities for obtaining RNA-based therapeutics. For the heart, RNA therapies can be developed that stimulate endogenous repair after cardiac damage. Applications in this area include acute cardioprotection after ischemia or cancer chemotherapy, therapeutic angiogenesis to promote new blood vessel formation, regeneration to form new cardiac mass, and editing of mutations to cure inherited cardiac disease. While the potential of RNA therapeutics for all these conditions is exciting, the field is still in its infancy. A number of roadblocks need to be overcome for RNA therapies to become effective, in particular, related to the problem of delivering RNA medicines into the cells and targeting them specifically to the heart.
Topics: Heart; Regeneration; RNA, Antisense; Aptamers, Nucleotide; RNA Interference; RNA, Guide, CRISPR-Cas Systems; Gene Editing; Humans; Animals
PubMed: 37440203
DOI: 10.1093/stcltm/szad038 -
Trends in Pharmacological Sciences Oct 2020RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains... (Review)
Review
RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains identifying a safe and effective delivery system. Studies investigating RNA therapeutics in pulmonary diseases have rapidly expanded and drug administration by inhalation allows the direct delivery of RNA therapeutics to the target site of action while minimizing systemic exposure. In this review, we highlight recent developments in pulmonary RNA delivery systems with the use of nonviral vectors. We also discuss the major knowledge gaps that require thorough investigation and provide insights that will help advance this exciting field towards the bedside.
Topics: Administration, Inhalation; Humans; RNA; RNA Interference; RNA, Small Interfering
PubMed: 32893004
DOI: 10.1016/j.tips.2020.08.002