Nanoparticle delivery systems for siRNA-based therapeutics

2016 ◽  
Vol 4 (41) ◽  
pp. 6620-6639 ◽  
Author(s):  
Jinming Li ◽  
Shanshan Xue ◽  
Zong-Wan Mao
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Delivery Systems ◽  
Regulatory Process ◽  
Transcriptional Gene Silencing ◽  
Double Stranded Rna ◽  
Nanoparticle Delivery ◽  
Naturally Occurring ◽  
Post Transcriptional Gene Silencing

RNA interference (RNAi) is a naturally occurring endogenous regulatory process in which the short double-stranded RNA causes sequence-specific post-transcriptional gene silencing.

scholarly journals Viroids as a Tool to Study RNA-Directed DNA Methylation in Plants

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1187
Author(s):  
Michael Wassenegger ◽  
Athanasios Dalakouras
Keyword(s):  
Dna Methylation ◽  
Rna Interference ◽  
Gene Silencing ◽  
Plant Cells ◽  
Transcriptional Gene Silencing ◽  
Rnai Machinery ◽  
Double Stranded Rna ◽  
Post Transcriptional Gene Silencing ◽  
Cumulative Amount

Viroids are plant pathogenic, circular, non-coding, single-stranded RNAs (ssRNAs). Members of the Pospiviroidae family replicate in the nucleus of plant cells through double-stranded RNA (dsRNA) intermediates, thus triggering the host’s RNA interference (RNAi) machinery. In plants, the two RNAi pillars are Post-Transcriptional Gene Silencing (PTGS) and RNA-directed DNA Methylation (RdDM), and the latter has the potential to trigger Transcriptional Gene Silencing (TGS). Over the last three decades, the employment of viroid-based systems has immensely contributed to our understanding of both of these RNAi facets. In this review, we highlight the role of Pospiviroidae in the discovery of RdDM, expound the gradual elucidation through the years of the diverse array of RdDM’s mechanistic details and propose a revised RdDM model based on the cumulative amount of evidence from viroid and non-viroid systems.

scholarly journals RNA interference: advances and questions

2002 ◽  
Vol 357 (1417) ◽  
pp. 65-70 ◽  
Author(s):  
Elisabetta Ullu ◽  
Appolinaire Djikeng ◽  
Huafang Shi ◽  
Christian Tschudi
Keyword(s):  
Rna Interference ◽  
Gene Silencing ◽  
Trypanosoma Brucei ◽  
Gene Function ◽  
Protozoan Parasite ◽  
Transcriptional Gene Silencing ◽  
Eukaryotic Lineage ◽  
Powerful Method ◽  
Double Stranded Rna ◽  
Post Transcriptional Gene Silencing

In animals and protozoa gene–specific double–stranded RNA triggers the degradation of homologous cellular RNAs, the phenomenon of RNA interference (RNAi). RNAi has been shown to represent a novel paradigm in eukaryotic biology and a powerful method for studying gene function. Here we discuss RNAi in terms of its mechanism, its relationship to other post–transcriptional gene silencing phenomena in plants and fungi, its connection to retroposon silencing and possibly to translation, and its biological role. Among the organisms where RNAi has been demonstrated the protozoan parasite Trypanosoma brucei represents the most ancient branch of the eukaryotic lineage. We provide a synopsis of what is currently known about RNAi in T. brucei and outline the recent advances that make RNAi the method of choice to disrupt gene function in these organisms.

An Introduction to Rna-Mediated Gene Silencing

2005 ◽  
Vol 88 (1) ◽  
pp. 49-69 ◽  
Author(s):  
Mark Geanacopoulos
Keyword(s):  
Gene Silencing ◽  
Careful Analysis ◽  
Transcriptional Gene Silencing ◽  
Double Stranded Rna ◽  
Endogenous Gene ◽  
Short Rnas ◽  
Post Transcriptional Gene Silencing ◽  
Endogenous Genes ◽  
Surveillance Mechanism ◽  
Broad Overview

Careful analysis of cases where introduction of additional copies of endogenous genes caused coordinate silencing of both the transgene and the endogenous gene laid the ground work for the discovery of RNA-mediated silencing. Silencing begins with the expression and recognition of double-stranded RNA, which is cleaved into short RNAs that recognize, by complementarity, sequences that are targets for down regulation. An RNA target can be regarded (post-transcriptional gene silencing), but the small RNAs can also direct the sequence-specific modification of DNA and chromatin. RNA-mediated gene silencing in eukaryotes may have originated as surveillance mechanism to protect the organism from transposable elements and viruses and then evolved to specify chromosomal modifications and to regulate expression of a significant fraction of endogenous genes by microRNAs. This review seeks to furnish the student and non-expert with some idea of how RNA-mediated silencing was discovered and a broad overview of the present state of knowledge.

scholarly journals Generation of Virus- and dsRNA-Derived siRNAs with Species-Dependent Length in Insects

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 738 ◽  
Author(s):  
Dulce Santos ◽  
Lina Mingels ◽  
Elise Vogel ◽  
Luoluo Wang ◽  
Olivier Christiaens ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Control Strategies ◽  
Length Distribution ◽  
Future Research ◽  
Transcriptional Gene Silencing ◽  
Viral Origin ◽  
Double Stranded Rna ◽  
Endogenous Gene ◽  
Post Transcriptional Gene Silencing ◽  
Triggering Mechanisms

Double-stranded RNA (dsRNA) molecules of viral origin trigger a post-transcriptional gene-silencing mechanism called RNA interference (RNAi). Specifically, virally derived dsRNA is recognized and cleaved by the enzyme Dicer2 into short interfering RNAs (siRNAs), which further direct sequence-specific RNA silencing, ultimately silencing replication of the virus. Notably, RNAi can also be artificially triggered by the delivery of gene-specific dsRNA, thereby leading to endogenous gene silencing. This is a widely used technology that holds great potential to contribute to novel pest control strategies. In this regard, research efforts have been set to find methods to efficiently trigger RNAi in the field. In this article, we demonstrate the generation of dsRNA- and/or virus-derived siRNAs—the main RNAi effectors—in six insect species belonging to five economically important orders (Lepidoptera, Orthoptera, Hymenoptera, Coleoptera, and Diptera). In addition, we describe that the siRNA length distribution is species-dependent. Taken together, our results reveal interspecies variability in the (antiviral) RNAi mechanism in insects and show promise to contribute to future research on (viral-based) RNAi-triggering mechanisms in this class of animals.

scholarly journals Antiviral innate immune response of RNA interference

2014 ◽  
Vol 8 (07) ◽  
pp. 804-810 ◽  
Author(s):  
Abubaker Sidahmed ◽  
Shaza Abdalla ◽  
Salahedin Mahmud ◽  
Bruce Wilkie
Keyword(s):  
Immune Response ◽  
Rna Interference ◽  
Viral Infection ◽  
Gene Silencing ◽  
Immune Defense ◽  
Innate Immune ◽  
Transcriptional Gene Silencing ◽  
Antiviral Defense ◽  
Post Transcriptional Gene Silencing ◽  
Short Period

RNA interference (RNAi) is an ancient, natural process conserved among species from different kingdoms. RNAi is a transcriptional and post-transcriptional gene silencing mechanism in which, double-stranded RNA or hairpin RNA is cleaved by an RNase III-type enzyme called Dicer into small interfering RNA duplex. This subsequently directs sequence-specific, homology dependent, Watson-Crick base-pairing post-transcriptional gene silencing by binding to its complementary RNA and initiating its elimination through degradation or by persuading translational inhibition. In plants, worms, and insects, RNAi is the main and strong antiviral defense mechanism. It is clear that RNAi silencing, contributes in restriction of viral infection in vertebrates. In a short period, RNAi has progressed to become a significant experimental tool for the analysis of gene function and target validation in mammalian systems. In addition, RNA silencing has then been found to be involved in translational repression, transcriptional inhibition, and DNA degradation. RNAi machinery required for robust RNAi-mediated antiviral response are conserved throughout evolution in mammals and plays a crucial role in antiviral defense of invertebrates, but despite these important functions RNAi contribution to mammalian antiviral innate immune defense has been underestimated and disputed. In this article, we review the literature concerning the roles of RNAi as components of innate immune system in mammals and how, the RNAi is currently one of the most hopeful new advances toward disease therapy. This review highlights the potential of RNAi as a therapeutic strategy for viral infection and gene regulation to modulate host immune response to viral infection.

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