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Trends in Ecology & Evolution Oct 2008Small interfering RNAs (siRNAs) and genome-encoded microRNAs (miRNAs) silence genes via complementary interactions with mRNAs. With thousands of miRNA genes identified... (Review)
Review
Small interfering RNAs (siRNAs) and genome-encoded microRNAs (miRNAs) silence genes via complementary interactions with mRNAs. With thousands of miRNA genes identified and genome sequences of diverse eukaryotes available for comparison, the opportunity emerges for insights into the origin and evolution of RNA interference (RNAi). The miRNA repertoires of plants and animals appear to have evolved independently. However, conservation of the key proteins involved in RNAi suggests that the last common ancestor of modern eukaryotes possessed siRNA-based mechanisms. Prokaryotes have an RNAi-like defense system that is functionally analogous but not homologous to eukaryotic RNAi. The protein machinery of eukaryotic RNAi seems to have been pieced together from ancestral archaeal, bacterial and phage proteins that are involved in DNA repair and RNA processing.
Topics: Animals; Biological Evolution; Eukaryotic Cells; Gene Expression Regulation; Plants; RNA Interference; RNA, Small Interfering
PubMed: 18715673
DOI: 10.1016/j.tree.2008.06.005 -
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 -
International Journal of Cancer Jan 2020
Topics: Humans; Publishing; RNA Interference; RNA, Small Interfering
PubMed: 31454067
DOI: 10.1002/ijc.32641 -
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 -
Philosophical Transactions of the Royal... Nov 2018Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for... (Review)
Review
Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for degradation? This requires a system that is highly adaptable, and at the same time highly specific. Current data suggest that perturbation of transcription patterns by transposon insertions could be detected by the RNAi surveillance pathway. Multiple transposon insertions might generate sufficient amounts of primal small RNAs to initiate generation of secondary small RNAs and silencing. At the same time primal small RNAs need to be constantly degraded to reduce the level of noise small RNAs below the threshold required for initiation of silencing. Failure in RNA degradation results in loss of fidelity of small RNA pathways and silencing of ectopic targets.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.
Topics: DNA Transposable Elements; Eukaryota; RNA; RNA Interference
PubMed: 30397104
DOI: 10.1098/rstb.2018.0168 -
Practical Neurology Apr 2018Many genetic neurological diseases result from the dysfunction of single proteins. Genetic therapies aim to modify these disease-associated proteins by targeting the RNA... (Review)
Review
Many genetic neurological diseases result from the dysfunction of single proteins. Genetic therapies aim to modify these disease-associated proteins by targeting the RNA and DNA precursors. This review provides a brief overview of the main types of genetic therapies, with a focus on antisense oligonucleotides (ASOs) and RNA interference (RNAi). We use examples of new genetic therapies for spinal muscular atrophy, Duchenne muscular dystrophy and familial amyloid polyneuropathy to highlight the different mechanisms of action of ASOs and RNAi.
Topics: Genetic Therapy; Humans; Oligodeoxyribonucleotides, Antisense; RNA Interference
PubMed: 29455156
DOI: 10.1136/practneurol-2017-001764 -
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 Oct 2023Shrimp aquaculture has become a vital industry, meeting the growing global demand for seafood. Shrimp viral diseases have posed significant challenges to the aquaculture... (Review)
Review
Shrimp aquaculture has become a vital industry, meeting the growing global demand for seafood. Shrimp viral diseases have posed significant challenges to the aquaculture industry, causing major economic losses worldwide. Conventional treatment methods have proven to be ineffective in controlling these diseases. However, recent advances in RNA interference (RNAi) technology have opened new possibilities for combating shrimp viral diseases. This cutting-edge technology uses cellular machinery to silence specific viral genes, preventing viral replication and spread. Numerous studies have shown the effectiveness of RNAi-based therapies in various model organisms, paving the way for their use in shrimp health. By precisely targeting viral pathogens, RNAi has the potential to provide a sustainable and environmentally friendly solution to combat viral diseases in shrimp aquaculture. This review paper provides an overview of RNAi-based therapy and its potential as a game-changer for shrimp viral diseases. We discuss the principles of RNAi, its application in combating viral infections, and the current progress made in RNAi-based therapy for shrimp viral diseases. We also address the challenges and prospects of this innovative approach.
Topics: Animals; RNAi Therapeutics; RNA Interference; Virus Diseases; Crustacea; Aquaculture
PubMed: 37896827
DOI: 10.3390/v15102050 -
Circulation Jan 2019Despite the availability of proven treatments for some patients with heart failure (HF), many patients—particularly those with HF and preserved ejection fraction...
Despite the availability of proven treatments for some patients with heart failure (HF), many patients—particularly those with HF and preserved ejection fraction (HFpEF)—remain difficult to treat, resulting in persistently high morbidity and mortality in the majority of HF patients. The lack of effective treatments, disappointing results of many HF randomized clinical trials (RCT), and variable treatment responses even for proven therapies are all possible reasons for the poor prognosis of HF patients. In the context of this backdrop, it is not surprising that there has been growing interest and enthusiasm for “precision medicine” in order to improve outcomes for patients who suffer from the HF syndrome.
Topics: Amyloidosis; Heart; Humans; Prealbumin; RNA Interference; RNA, Small Interfering
PubMed: 30664380
DOI: 10.1161/CIRCULATIONAHA.118.037593 -
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