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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 -
British Journal of Pharmacology Apr 2021RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the... (Review)
Review
RNAi effectors (e.g. siRNA, shRNA and miRNA) can trigger the silencing of specific genes causing alteration of genomic functions becoming a new therapeutic area for the treatment of infectious diseases, neurodegenerative disorders and cancer. In cancer treatment, RNAi effectors showed potential immunomodulatory actions by down-regulating immuno-suppressive proteins, such as PD-1 and CTLA-4, which restrict immune cell function and present challenges in cancer immunotherapy. Therefore, compared with extracellular targeting by antibodies, RNAi-mediated cell-intrinsic disruption of inhibitory pathways in immune cells could promote an increased anti-tumour immune response. Along with non-viral vectors, DNA-based RNAi strategies might be a more promising method for immunomodulation to silence multiple inhibitory pathways in T cells than immune checkpoint blockade antibodies. Thus, in this review, we discuss diverse RNAi implementation strategies, with recent viral and non-viral mediated RNAi synergism to immunotherapy that augments the anti-tumour immunity. Finally, we provide the current progress of RNAi in clinical pipeline.
Topics: Humans; Immunotherapy; MicroRNAs; Neoplasms; RNA Interference; RNA, Small Interfering
PubMed: 33608889
DOI: 10.1111/bph.15414 -
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 -
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 -
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 -
Developmental Cell Feb 2011Small non-coding RNAs, through association with Argonaute protein family members, have a variety of functions during the development of an organism. Although there is... (Review)
Review
Small non-coding RNAs, through association with Argonaute protein family members, have a variety of functions during the development of an organism. Although there is increased mechanistic understanding of the RNA interference (RNAi) pathways surrounding these small RNAs, how their effects are modulated by subcellular compartmentalization and cross-pathway functional interactions is only beginning to be explored. This review examines the current understanding of these aspects of RNAi pathways and the biological functions of these pathways.
Topics: Animals; Cell Compartmentation; Cell Differentiation; Cell Nucleus; Meiosis; RNA Interference; Signal Transduction
PubMed: 21316584
DOI: 10.1016/j.devcel.2011.01.012 -
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 -
Trends in Pharmacological Sciences Oct 2020RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains... (Review)
Review
RNA-based medicine is receiving growing attention for its diverse roles and potential therapeutic capacity. The largest obstacle in its clinical translation remains identifying a safe and effective delivery system. Studies investigating RNA therapeutics in pulmonary diseases have rapidly expanded and drug administration by inhalation allows the direct delivery of RNA therapeutics to the target site of action while minimizing systemic exposure. In this review, we highlight recent developments in pulmonary RNA delivery systems with the use of nonviral vectors. We also discuss the major knowledge gaps that require thorough investigation and provide insights that will help advance this exciting field towards the bedside.
Topics: Administration, Inhalation; Humans; RNA; RNA Interference; RNA, Small Interfering
PubMed: 32893004
DOI: 10.1016/j.tips.2020.08.002 -
The AAPS Journal Mar 2010Recently, the RNA interference (RNAi) pathway has become the target of small molecule inhibitors and activators. RNAi has been well established as a research tool in the... (Review)
Review
Recently, the RNA interference (RNAi) pathway has become the target of small molecule inhibitors and activators. RNAi has been well established as a research tool in the sequence-specific silencing of genes in eukaryotic cells and organisms by using exogenous, small, double-stranded RNA molecules of approximately 20 nucleotides. Moreover, a recently discovered post-transcriptional gene regulatory mechanism employs microRNAs (miRNAs), a class of endogenously expressed small RNA molecules, which are processed via the RNAi pathway. The chemical modulation of RNAi has important therapeutic relevance, because a wide range of miRNAs has been linked to a variety of human diseases, especially cancer. Thus, the activation of tumor-suppressive miRNAs and the inhibition of oncogenic miRNAs by small molecules have the potential to provide a fundamentally new approach for the development of cancer therapeutics.
Topics: Animals; Humans; MicroRNAs; RNA Interference; RNA, Small Interfering
PubMed: 19937410
DOI: 10.1208/s12248-009-9159-3 -
Journal of Biology Nov 2008The efficiency of RNA interference varies between different organisms, even among nematodes. A recent report of successful RNA interference in the nematode Panagrolaimus... (Review)
Review
The efficiency of RNA interference varies between different organisms, even among nematodes. A recent report of successful RNA interference in the nematode Panagrolaimus superbus in BMC Molecular Biology has implications for the comparative study of the functional genomics of nematode species, and prompts reflections on the choice of Caenorhabditis elegans as a model organism.
Topics: Animals; Caenorhabditis elegans; Eukaryota; Genome, Helminth; RNA Interference; Rhabditida
PubMed: 19014674
DOI: 10.1186/jbiol97