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The New England Journal of Medicine Oct 2023
Topics: Humans; RNA Interference; Hypertension; Hypertension, Renal
PubMed: 37819963
DOI: 10.1056/NEJMc2310167 -
The New England Journal of Medicine Oct 2023
Topics: Humans; RNA Interference; Hypertension; Hypertension, Renal
PubMed: 37819962
DOI: 10.1056/NEJMc2310167 -
ELife Aug 2023Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target...
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
Topics: RNA Interference; RNA, Small Interfering
PubMed: 37552050
DOI: 10.7554/eLife.84792 -
The New England Journal of Medicine Oct 2023
Topics: Humans; RNA Interference; Hypertension
PubMed: 37819965
DOI: 10.1056/NEJMc2310167 -
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 -
Current Gene Therapy 2020In recent years, RNA interference technology has been extensively studied for its therapeutic potential against a wide variety of diseases. It aims to silence the... (Review)
Review
In recent years, RNA interference technology has been extensively studied for its therapeutic potential against a wide variety of diseases. It aims to silence the expression of undesired genes associated with the target disease by the administration of RNA interference agents. However, these agents (nucleic acids) are unstable in the circulatory system and lack target specificity. Drug delivery systems are, therefore, crucial for the successful practice of the technique. A wide array of delivery systems has been developed to conquer these challenges, such as viral vectors, inorganic drug carriers, polymeric carriers and lipid-based carriers, with, however, significant limitations. In addition to the existing technologies, novel, innovative drug delivery systems, such as the configurable xenobot, are emerging at a rapid pace and have the potential to take the realm of biomedicine to the next level. This review summarizes technical difficulties in the development of drug delivery systems and current technologies developed for delivering RNAi agents with a discussion on their limitations.
Topics: Drug Delivery Systems; Genetic Diseases, Inborn; Humans; Nucleic Acids; Polymers; RNA Interference
PubMed: 33019930
DOI: 10.2174/1566523220666201005110726 -
Wiley Interdisciplinary Reviews. RNA 2015Throughout the domains of life, transposon activity represents a serious threat to genome integrity and evolution has realized different molecular mechanisms that aim to... (Review)
Review
Throughout the domains of life, transposon activity represents a serious threat to genome integrity and evolution has realized different molecular mechanisms that aim to inhibit the transposition of mobile DNA. Small noncoding RNAs that function as guides for Argonaute effector proteins represent a key feature of so-called RNA interference (RNAi) pathways and specialized RNAi pathways exist to repress transposon activity on the transcriptional and posttranscriptional level. Transposon transcription can be diminished by targeted DNA methylation or chromatin remodeling via repressive Histone modifications. Posttranscriptional transposon silencing bases on degradation of transposon transcripts to prevent either reverse transcription followed by genomic reintegration or translation into proteins that mediate the transposition process. In plants, Argonaute-like proteins guided by short interfering RNAs (siRNAs) are essential for transposon repression on the epigenetic and posttranscriptional level. In the germline of animals, these tasks are often assumed by a second subclass of Argonaute proteins referred to as Piwi-like proteins, which bind a distinct class of small noncoding RNAs named piwi-interacting RNAs (piRNAs). Though the principals of RNAi pathways are essentially the same in all eukaryotic organisms, remarkable differences can be observed even in closely related species reflecting the astonishing plasticity and diversity of these pathways.
Topics: Animals; DNA Transposable Elements; Humans; RNA; RNA Interference
PubMed: 26439796
DOI: 10.1002/wrna.1310 -
Journal of Cellular Biochemistry Jan 2018The ability to develop efficient and versatile technologies for manipulating gene expression is a fundamental issue both in biotechnology and therapeutics. The... (Review)
Review
The ability to develop efficient and versatile technologies for manipulating gene expression is a fundamental issue both in biotechnology and therapeutics. The endogenous RNA interference (RNAi) pathway which mediates gene silencing was discovered at the end of the 20th century and it is nowadays considered as an essential strategy for knockdown of specific genes and for studying gene function. Remarkably, during the past decade, a RNA-induced mechanism of gene activation has also been reported. Likewise RNAi, the RNA activation (RNAa) process is also mediated by sequence-specific double-stranded RNA (dsRNA) molecules, and interesting resemblances between both RNA-based transcriptional mechanisms have been described. Small activating RNAs (saRNAs) and related molecules have been used for targeting of genes in species that are as different as nematodes and humans, and similar dsRNA-induced activation phenomena have also been observed in plants. The aim of this letter is to highlight recent molecular insights into yet unexplored RNAa mechanism and its potential for manipulating transcriptional activity. J. Cell. Biochem. 119: 247-249, 2018. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Genetic Engineering; Genome, Human; Humans; RNA Interference
PubMed: 28636278
DOI: 10.1002/jcb.26228 -
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