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Chembiochem : a European Journal of... Feb 2024Ribonucleic acid (RNA) plays a pivotal role in gene regulation and protein biosynthesis. Interfering the physiological function of key RNAs to induce cell apoptosis... (Review)
Review
Ribonucleic acid (RNA) plays a pivotal role in gene regulation and protein biosynthesis. Interfering the physiological function of key RNAs to induce cell apoptosis holds great promise for cancer treatment. Many RNA-targeted anti-cancer strategies have emerged continuously. Among them, RNA interference (RNAi) has been recognized as a promising therapeutic modality for various disease treatments. Nevertheless, the primary obstacle in siRNA delivery-escaping the endosome and crossing the plasma membrane severely impedes its therapeutic potential. Thus far, a variety of nanosystems as well as carrier-free bioconjugation for siRNA delivery have been developed and employed to enhance the drug delivery and anti-tumor efficiency. Besides, the use of small molecules to target specific RNA structures and disrupt their function, along with the covalent modification of RNA, has also drawn tremendous attention recently owing to high therapeutic efficacy. In this review, we will provide an overview of recent progress in RNA-targeted cancer therapy including various siRNA delivery strategies, RNA-targeting small molecules, and newly emerged covalent RNA modification. Finally, challenges and future perspectives faced in this research field will be discussed.
Topics: Humans; RNA, Small Interfering; RNA Interference; Neoplasms; Drug Delivery Systems; Gene Expression Regulation
PubMed: 37961028
DOI: 10.1002/cbic.202300633 -
Artificial Organs Feb 2022Organ transplantation is the definitive treatment for end-stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ... (Review)
Review
Organ transplantation is the definitive treatment for end-stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ transplants. As such, there is a need for gene therapy and gene modulation strategies in the organ transplantation setting to prevent rejection, expand the donor pool of available organs, and attenuate ischemia-reperfusion damage. As we are entering an era of "precision medicine," the organ transplant field is becoming equipped with the tools necessary to personalize and optimize organs designed specifically to withstand injurious pathways that occur during transplantation, such that the concept of "designer organs" will be a reality in the near future. In this review, we highlight the recent progress using gene knockout and knock-in strategies used mainly in the context of xenotransplantation. We also discuss advancements in CRISPR-Cas9 gene editing and RNA interference in relation to organ transplantation. Lastly, we discuss the exciting future implications of customized gene therapy in the transplantation setting, and its ability to potentially create a future where organs intended for transplant are personalized to maximize both graft and patient survival.
Topics: Animals; Gene Knock-In Techniques; Gene Knockout Techniques; Genetic Therapy; Graft Rejection; Humans; Organ Preservation; Organ Transplantation; Perfusion; Precision Medicine; RNA Interference; Transplantation, Heterologous
PubMed: 35014719
DOI: 10.1111/aor.14151 -
Journal of Integrative Plant Biology Feb 2022RNA silencing (or RNA interference, RNAi) is a conserved mechanism for regulating gene expression in eukaryotes. The discovery of natural trans-kingdom RNAi indicated... (Review)
Review
RNA silencing (or RNA interference, RNAi) is a conserved mechanism for regulating gene expression in eukaryotes. The discovery of natural trans-kingdom RNAi indicated that small RNAs act as signaling molecules and enable communication between organisms in different kingdoms. The phenomenon and potential mechanisms of trans-kingdom RNAi are among the most exciting research topics. To better understand trans-kingdom RNAi, we review the history of the discovery and elucidation of RNAi mechanisms. Based on canonical RNAi mechanisms, we summarize the major points of divergence around RNAi pathways in the main eukaryotes' kingdoms, including plants, animals, and fungi. We review the representative incidents associated with the mechanisms and applications of trans-kingdom RNAi in crop protection, and discuss the critical factors that should be considered to develop successful trans-kingdom RNAi-based crop protection strategies.
Topics: Animals; Fungi; Plants; RNA Interference; RNA, Small Interfering
PubMed: 34964265
DOI: 10.1111/jipb.13213 -
European Journal of Clinical... Oct 2023Small interference RNA (siRNA) has emerged as the most desired method for researchers and clinicians who wish to silence a specific gene of interest and has been... (Review)
Review
BACKGROUND
Small interference RNA (siRNA) has emerged as the most desired method for researchers and clinicians who wish to silence a specific gene of interest and has been extensively developed as a therapeutic agent. This review points to collecting all clinical trials on siRNA and understanding its benefits, pharmacokinetics and safety by reading articles published in the last 5 years.
MATERIALS AND METHODS
Searching in the PubMed database using 'siRNA' and 'in vivo' with limits to articles published in the previous 5 years, article type 'clinical trials' and language 'English' to acquire papers on in vivo studies on siRNA approaches. Features of siRNA clinical trials registered at https://clinicaltrials.gov/ were analysed.
RESULTS
So far, 55 clinical studies have been published on siRNA. Many published clinical trials on siRNA showed tolerability, safety and effectiveness in treating cancers like breast, lung, colon, and other organs and other diseases like viral infections and hereditary diseases. Many different routes of administration can silence many genes at the same time. Limitations and uncertainties associated with siRNA treatment include the effectiveness of cellular uptake, precise targeting of the intended tissue or cell and prompt elimination from the body.
CONCLUSIONS
The siRNA or RNAi method will be one of the most critical and influential techniques to fight against many different diseases. Although the RNAi approach has certain advantages, it also has limitations concerning clinical applications. Overcoming these limitations remains a daunting challenge.
Topics: Humans; RNA Interference; RNA, Small Interfering; Lung; Neoplasms; Virus Diseases
PubMed: 37309221
DOI: 10.1111/eci.14039 -
Current Opinion in Plant Biology Apr 2021Expression of insect-targeted RNA interference (RNAi) constructs in transgenic plants is a promising approach for agricultural pest control. Compared to conventional... (Review)
Review
Expression of insect-targeted RNA interference (RNAi) constructs in transgenic plants is a promising approach for agricultural pest control. Compared to conventional chemical insecticides, RNAi target specificity is high and the potential for negative environmental effects is low. However, although numerous laboratory studies show insect growth inhibition by double stranded RNA or artificial microRNA, few of these constructs have been moved into commercial application as genetically engineered plants. Variation in RNA degradation, uptake, processing, and systemic transport in insects can influence interspecific and intraspecific differences in RNAi efficacy and the development of resistance to RNAi in agricultural settings. Further research is needed, both to identify optimal gene targets for efficient RNAi in pest species and to reduce the potential for off-target effects in beneficial species.
Topics: Animals; Insecta; Plants, Genetically Modified; RNA Interference; RNA, Double-Stranded; RNA, Plant
PubMed: 33639339
DOI: 10.1016/j.pbi.2021.102029 -
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 -
Current Opinion in Microbiology Oct 2021Nowadays, the focus of mycovirology research has expanded from plant pathogenic fungi and mycovirus mediated hypovirulence to include insect and human pathogenic fungi... (Review)
Review
Nowadays, the focus of mycovirology research has expanded from plant pathogenic fungi and mycovirus mediated hypovirulence to include insect and human pathogenic fungi together with a range of mycovirus mediated phenotypes, such as hypervirulence, control of endophytic traits, regulation of metabolite production and drug resistance. In fungus-mycovirus-environmental interactions, the environment and both abiotic and biotic factors play crucial roles in whether and how mycovirus mediated phenotypes are manifest. Mycovirus infections result in alterations in the host transcriptome profile, via protein-protein interactions and triggering of antiviral RNA silencing in the fungus. These alterations, in combination with the environmental factors, may result in desirable phenotypic traits for the host, for us and in some cases for both.
Topics: Fungal Viruses; Fungi; Humans; Plant Diseases; Plants; RNA Interference; RNA Viruses; Transcriptome
PubMed: 34102567
DOI: 10.1016/j.mib.2021.05.007 -
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 -
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 -
Nature Chemical Biology Jun 2022
Topics: RNA Interference; Nicotiana
PubMed: 35618932
DOI: 10.1038/s41589-022-01058-8