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FEBS Letters Aug 2014RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by long double-stranded RNA (dsRNA). RNAi is an ancient eukaryotic defense mechanism against... (Review)
Review
RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by long double-stranded RNA (dsRNA). RNAi is an ancient eukaryotic defense mechanism against viruses and mobile elements. In mammals, endogenous RNAi was outstripped during evolution by the current innate and acquired immunity. The RNAi apparatus, which remains essentially intact, serves mostly the microRNA pathway, which regulates endogenous gene expression. Remarkably, several recent publications brought the mammalian endogenous RNAi pathway back into the spotlight. Here, I will provide an up-to-date review of the mammalian endogenous RNAi pathway with a focus on its defensive role and overlaps with miRNA and piRNA pathways.
Topics: Animals; Humans; RNA Interference; RNA, Small Interfering
PubMed: 24873877
DOI: 10.1016/j.febslet.2014.05.030 -
Nature Communications Dec 2018Recognition and repression of RNA targets by Argonaute proteins guided by small RNAs is the essence of RNA interference in eukaryotes. Argonaute proteins with diverse... (Review)
Review
Recognition and repression of RNA targets by Argonaute proteins guided by small RNAs is the essence of RNA interference in eukaryotes. Argonaute proteins with diverse structures are also found in many bacterial and archaeal genomes. Recent studies revealed that, similarly to their eukaryotic counterparts, prokaryotic Argonautes (pAgos) may function in cell defense against foreign genetic elements but, in contrast, preferably act on DNA targets. Many crucial details of the pAgo action, and the roles of a plethora of pAgos with non-conventional architecture remain unknown. Here, we review available structural and biochemical data on pAgos and discuss their possible functions in host defense and other genetic processes in prokaryotic cells.
Topics: Argonaute Proteins; Catalysis; Catalytic Domain; DNA; Eukaryota; Eukaryotic Cells; Genetic Engineering; Immune System; Prokaryotic Cells; Protein Binding; Protein Domains; Protein Interaction Domains and Motifs; RNA; RNA Interference; RNA, Small Interfering
PubMed: 30514832
DOI: 10.1038/s41467-018-07449-7 -
Molecular Cancer Jul 2017RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the... (Review)
Review
BACKGROUND
RNA interference (RNAi), a newly developed method in which RNA molecules inhibit gene expression, has recently received considerable research attention. In the development of RNAi-based therapies, nanoparticles, which have distinctive size effects along with facile modification strategies and are capable of mediating effective RNAi with targeting potential, are attracting extensive interest.
OBJECTIVE
This review presents an overview of the mechanisms of RNAi molecules in gene therapy and the different nanoparticles used to deliver RNAi molecules; briefly describes the current uses of RNAi in cancer therapy along with the nano-based delivery of RNA molecules in previous studies; and highlights some other carriers that have been applied in clinical settings. Finally, we discuss the nano-based delivery of RNAi therapeutics in preclinical development, including the current status and limitations of anti-cancer treatment.
CONCLUSION
With the growing number of RNAi therapeutics entering the clinical phase, various nanocarriers are expected to play important roles in the delivery of RNAi molecules for cancer therapeutics.
Topics: Drug Delivery Systems; Genetic Therapy; Humans; Nanoparticles; Neoplasms; RNA Interference
PubMed: 28754120
DOI: 10.1186/s12943-017-0683-y -
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 -
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 -
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 -
Viruses Dec 2017HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be... (Review)
Review
HIV-1 drug therapies can prevent disease progression but cannot eliminate HIV-1 viruses from an infected individual. While there is hope that elimination of HIV-1 can be achieved, several approaches to reach a functional cure (control of HIV-1 replication in the absence of drug therapy) are also under investigation. One of these approaches is the transplant of HIV-1 resistant cells expressing anti-HIV-1 RNAs, proteins or peptides. Small RNAs that use RNA interference pathways to target HIV-1 replication have emerged as competitive candidates for cell transplant therapy and have been included in all gene combinations that have so far entered clinical trials. Here, we review RNA interference pathways in mammalian cells and the design of therapeutic small RNAs that use these pathways to target pathogenic RNA sequences. Studies that have been performed to identify anti-HIV-1 RNA interference therapeutics are also reviewed and perspectives on their use in combination gene therapy to functionally cure HIV-1 infection are provided.
Topics: Anti-HIV Agents; Gene Expression Regulation, Viral; HIV Infections; HIV-1; Humans; RNA Interference; RNA, Small Interfering; RNAi Therapeutics; Virus Replication
PubMed: 29280961
DOI: 10.3390/v10010008 -
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