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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 -
Journal of Controlled Release :... Jul 2020Cancer remains one of the leading causes of death worldwide despite significant therapeutic advancements and improved detection methods. Nucleic acid (NA) therapeutics... (Review)
Review
Cancer remains one of the leading causes of death worldwide despite significant therapeutic advancements and improved detection methods. Nucleic acid (NA) therapeutics are receiving increasing attention for cancer management and cure. Indeed, ribonucleic acid (RNA) oligonucleotides (such as small interfering RNA (siRNA) and micro RNA (miRNA)), messenger RNA (mRNA) and deoxyribonucleic acid (DNA) (such as plasmidic DNA (pDNA) and minicircle DNA (mcDNA)), have demonstrated potential as novel therapeutic agents. The imposing prospects of NA-based therapeutics reside in their ability to act as key-players mediating cellular pathways and bestowing potent gene silencing properties, as in the case of RNA interference (RNAi) agents, or by promoting the expression of specific required proteins for disease management (pDNA, mcDNA and mRNA, for instance). However, efficient NA therapeutics delivery is seriously hampered by NA physicochemical features, low in vivo serum stability and compromised cellular internalization, which swiftly reduce their biological activities. Recently, nano-based systems emerged as suitable vehicles for NA delivery. This review covers NA-carrying micelleplexes as robust and multifunctional polymer-based NA delivery systems, as well as the specific in vivo challenges for successful NA delivery to cancer cells and their prospects to become clinical reality, followed by a critical analysis of the major in vivo micelleplex-based cancer-targeted strategies accomplished till the present day.
Topics: Drug Delivery Systems; Micelles; Neoplasms; Nucleic Acids; Polymers; RNA Interference; RNA, Small Interfering
PubMed: 32353488
DOI: 10.1016/j.jconrel.2020.04.041 -
Annual Review of Pharmacology and... 2016A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi... (Review)
Review
A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials. Continued positive results from these trials have helped bolster further attempts to develop clinically relevant RNAi therapies. With a wide variety of disease targets to choose from, the first RNAi therapeutic to be clinically approved is not far off. This review covers recently established and completed clinical trials.
Topics: Clinical Trials as Topic; Drug Delivery Systems; Humans; Pharmaceutical Preparations; RNA Interference
PubMed: 26738473
DOI: 10.1146/annurev-pharmtox-010715-103633 -
Expert Opinion on Biological Therapy Jan 2015Cells release extracellular vesicles to their surroundings to communicate with each other. Exosomes are a subgroup of 30 - 100-nm-sized extracellular vesicles,... (Review)
Review
INTRODUCTION
Cells release extracellular vesicles to their surroundings to communicate with each other. Exosomes are a subgroup of 30 - 100-nm-sized extracellular vesicles, originating from the endocytic pathway. They contain RNA molecules, proteins and lipids that can be transferred between cells. Exosomes have been found in several body fluids, indicating that this is a frequently used and tolerated system for cells to communicate RNA molecules and proteins over distances.
AREAS COVERED
It has been shown that patients with cancer have higher concentrations of exosomes in their blood and that these exosomes can carry tumor-specific molecules. Exosomes are, therefore, currently being evaluated for their potential use as biomarkers. Additionally, exosomes have been demonstrated to have the capacity to modulate immune responses. Therefore, exosomes are believed to be beneficial as a cell-free vaccine for cancer and infections. Further, as exosomes are the body's endogenous system for transport RNA, exosomes are also evaluated for their potential use as a therapeutic RNA delivery system. This review provides an overview of studies reporting diagnostic and therapeutic potential for exosomes.
EXPERT OPINION
The data reviewed here suggest that exosomes have the potential to be used for both diagnosis and therapy for several diseases in the future.
Topics: Biomarkers; Cancer Vaccines; Drug Delivery Systems; Exosomes; Gene Transfer Techniques; Humans; Neoplasms; Proteins; RNA Interference
PubMed: 25363342
DOI: 10.1517/14712598.2015.977250 -
Viruses May 2019The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In... (Review)
Review
The RNA interference (RNAi) pathway is a potent antiviral defense mechanism in plants and invertebrates, in response to which viruses evolved suppressors of RNAi. In mammals, the first line of defense is mediated by the type I interferon system (IFN); however, the degree to which RNAi contributes to antiviral defense is still not completely understood. Recent work suggests that antiviral RNAi is active in undifferentiated stem cells and that antiviral RNAi can be uncovered in differentiated cells in which the IFN system is inactive or in infections with viruses lacking putative viral suppressors of RNAi. In this review, we describe the mechanism of RNAi and its antiviral functions in insects and mammals. We draw parallels and highlight differences between (antiviral) RNAi in these classes of animals and discuss open questions for future research.
Topics: Animals; Antiviral Agents; Immunity, Innate; Insecta; Interferon Type I; Mammals; MicroRNAs; RNA Interference; RNA Viruses; RNA, Small Interfering; Viruses
PubMed: 31100912
DOI: 10.3390/v11050448 -
Expert Opinion on Biological Therapy 2015Despite considerable improvements in therapies, atherosclerotic cardiovascular diseases remain the leading cause of death worldwide. Therefore, in addition to current... (Review)
Review
INTRODUCTION
Despite considerable improvements in therapies, atherosclerotic cardiovascular diseases remain the leading cause of death worldwide. Therefore, in addition to current treatment options, new therapeutic approaches are still needed.
AREAS COVERED
In this review, novel gene and RNA interference-based therapy approaches and promising target genes for treating atherosclerosis are addressed. In addition, relevant animal models for the demonstration of the efficacy of different gene therapy applications, and current progress toward more efficient, targeted and safer gene transfer vectors are reviewed.
EXPERT OPINION
Atherosclerosis represents a complex multifactorial disease that is dependent on the interplay between lipoprotein metabolism, cellular reactions and inflammation. Recent advances and novel targets, especially in the field of RNA interference-based therapies, are very promising. However, it should be noted that the modulation of a particular gene is not as clearly associated with a complex polygenic disease as it is in the case of monogenic diseases. A deeper understanding of molecular mechanisms of atherosclerosis, further progress in vector development and the demonstration of treatment efficacy in relevant animal models will be required before gene therapy of atherosclerosis meets its clinical reality.
Topics: Animals; Atherosclerosis; Genetic Therapy; Genetic Vectors; Humans; RNA Interference; Treatment Outcome
PubMed: 26328616
DOI: 10.1517/14712598.2015.1084282 -
Nature Reviews. Nephrology Oct 2023
Topics: Humans; Antihypertensive Agents; RNA Interference; Hypertension
PubMed: 37612379
DOI: 10.1038/s41581-023-00765-2 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Apr 2021RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the... (Review)
Review
RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the antiviral strategy of host. Early studies reveal that invertebrates can use RNAi to resist viruses. However, if this mechanism exists in mammals is still controversial. The latest studies confirm that mammals do have the RNAi-based immunity, and researchers believe that RNAi-based antiviral immunity is a brand-new immunological mechanism that was neglected in the past. It is worthy to note that virus can also use RNAi to enhance its infectivity and immune escape in host cells. This review introduces the research history of RNAi-based antiviral immunity in animals and summarizes the main findings in this field. Last but not least, we indicate a series of unresolved questions about RNAi-based antiviral immunity, and explore the relationship between RNAi-based antiviral immunity and other innate immunological pathways. The virus-mediated RNAi pathway in animal is not only an interesting basic biology question, but also has important guiding roles in the development of antiviral drugs.
Topics: Animals; Antiviral Agents; Immunity, Innate; Mammals; RNA Interference; RNA, Small Interfering; RNA, Viral
PubMed: 33973438
DOI: 10.13345/j.cjb.200665 -
American Journal of Transplantation :... Apr 2020RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest.... (Review)
Review
RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest. In 2006, the discovery of RNAi was awarded the Nobel Prize in Medicine and its success has accumulated since. Gene silencing through RNAi has been used successfully in a broad range of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Here, genes related to ischemia-reperfusion injury (IRI) or graft rejection may be silenced to improve organ quality after transplantation. Several strategies have been used to deliver siRNA, and pretransplant machine perfusion presents a unique opportunity to deliver siRNA to the target organ during ex situ preservation. In this review, the potential of RNAi in the field of organ transplantation will be discussed. A brief overview on the discovery of RNAi, its mechanism, and limitations are included. In addition, studies using RNAi to target genes related to IRI in liver, kidney, lung, and heart transplantation are discussed.
Topics: Humans; Organ Transplantation; Perfusion; RNA Interference; RNA, Small Interfering; Reperfusion Injury
PubMed: 31680428
DOI: 10.1111/ajt.15689 -
Science China. Life Sciences Mar 2016In plants, post-transcriptional gene silencing (PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper... (Review)
Review
In plants, post-transcriptional gene silencing (PTGS) protects the genome from foreign genes and restricts the expression of certain endogenous genes for proper development. Here, we review the recent progress about how the unwanted PTGS is avoided in plants. As a decision-making step of PTGS, aberrant transcripts from most endogenous coding genes are strictly sorted to the bidirectional RNA decay pathways in cytoplasm but not to the short interference RNA (siRNA)-mediated PTGS, with the exception of a few development-relevant endogenous siRNA-producing genes. We also discuss a finely balanced PTGS threshold model that plants fully take advantage of the power of PTGS without self-harm.
Topics: Cytoplasm; Gene Expression Regulation, Plant; Gene Silencing; Plants; RNA Interference; RNA Stability; RNA, Plant; RNA, Small Interfering
PubMed: 26718356
DOI: 10.1007/s11427-015-4972-7