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Keywords = ncRNA drug delivery

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27 pages, 7126 KiB  
Review
Emerging Roles of ncRNAs in Type 2 Diabetes Mellitus: From Mechanisms to Drug Discovery
by Yue Yang and Hao Cheng
Biomolecules 2024, 14(11), 1364; https://doi.org/10.3390/biom14111364 - 27 Oct 2024
Viewed by 1712
Abstract
Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as a global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. [...] Read more.
Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as a global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. Growing evidence validates that non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as crucial regulators in multiple biological processes of T2DM, inspiring various potential targets and drug candidates. In this review, we summarize the current understanding of ncRNA roles in T2DM and discuss the potential use of ncRNAs as targets and active molecules for drug discovery. Full article
(This article belongs to the Collection Feature Papers in Section 'Molecular Medicine')
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36 pages, 3954 KiB  
Review
Non-Coding RNA-Targeted Therapy: A State-of-the-Art Review
by Francesco Nappi
Int. J. Mol. Sci. 2024, 25(7), 3630; https://doi.org/10.3390/ijms25073630 - 24 Mar 2024
Cited by 19 | Viewed by 3176
Abstract
The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease [...] Read more.
The use of non-coding RNAs (ncRNAs) as drug targets is being researched due to their discovery and their role in disease. Targeting ncRNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), is an attractive approach for treating various diseases, such as cardiovascular disease and cancer. This seminar discusses the current status of ncRNAs as therapeutic targets in different pathological conditions. Regarding miRNA-based drugs, this approach has made significant progress in preclinical and clinical testing for cardiovascular diseases, where the limitations of conventional pharmacotherapy are evident. The challenges of miRNA-based drugs, including specificity, delivery, and tolerability, will be discussed. New approaches to improve their success will be explored. Furthermore, it extensively discusses the potential development of targeted therapies for cardiovascular disease. Finally, this document reports on the recent advances in identifying and characterizing microRNAs, manipulating them, and translating them into clinical applications. It also addresses the challenges and perspectives towards clinical application. Full article
(This article belongs to the Special Issue Exosomes and Non-Coding RNA Research in Health and Disease)
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17 pages, 4414 KiB  
Article
Exploring the Genomic Landscape of Bacillus paranthracis PUMB_17 as a Proficient Phosphatidylcholine-Specific Phospholipase C Producer
by Vesselin Baev, Ivan Iliev, Yordan Stefanov, Marinela Tsankova, Mariana Marhova, Elena Apostolova, Mariyana Gozmanova, Galina Yahubyan and Sonya Kostadinova
Curr. Issues Mol. Biol. 2024, 46(3), 2497-2513; https://doi.org/10.3390/cimb46030158 - 14 Mar 2024
Viewed by 2284
Abstract
Phospholipases find versatile applications across industries, including detergent production, food modification, pharmaceuticals (especially in drug delivery systems), and cell signaling research. In this study, we present a strain of Bacillus paranthracis for the first time, demonstrating significant potential in the production of phosphatidylcholine-specific [...] Read more.
Phospholipases find versatile applications across industries, including detergent production, food modification, pharmaceuticals (especially in drug delivery systems), and cell signaling research. In this study, we present a strain of Bacillus paranthracis for the first time, demonstrating significant potential in the production of phosphatidylcholine-specific phospholipase C (PC-PLC). The investigation thoroughly examines the B. paranthracis PUMB_17 strain, focusing on the activity of PC-PLC and its purification process. Notably, the PUMB_17 strain displays extracellular PC-PLC production with high specific activity during the late exponential growth phase. To unravel the genetic makeup of PUMB_17, we employed nanopore-based whole-genome sequencing and subsequently conducted a detailed genome annotation. The genome comprises a solitary circular chromosome spanning 5,250,970 bp, featuring a guanine–cytosine ratio of 35.49. Additionally, two plasmids of sizes 64,250 bp and 5845 bp were identified. The annotation analysis reveals the presence of 5328 genes, encompassing 5186 protein-coding sequences, and 142 RNA genes, including 39 rRNAs, 103 tRNAs, and 5 ncRNAs. The aim of this study was to make a comprehensive genomic exploration that promises to enhance our understanding of the previously understudied and recently documented capabilities of Bacillus paranthracis and to shed light on a potential use of the strain in the industrial production of PC-PLC. Full article
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41 pages, 3221 KiB  
Review
Aptamers as Potential Therapeutic Tools for Ovarian Cancer: Advancements and Challenges
by Wojciech Szymanowski, Anna Szymanowska, Anna Bielawska, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo and Paola Amero
Cancers 2023, 15(21), 5300; https://doi.org/10.3390/cancers15215300 - 6 Nov 2023
Cited by 9 | Viewed by 2752
Abstract
Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of [...] Read more.
Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug delivery systems, enabling targeted delivery of therapeutic agents to cancer cells while minimizing off-target effects and reducing systemic toxicity. In the context of OC, the integration of aptamers with non-coding RNAs (ncRNAs) presents an opportunity for precise and efficient gene targeting. Additionally, the conjugation of aptamers with nanoparticles allows for accurate and targeted delivery of ncRNAs to specific cells, tissues, or organs. In this review, we will summarize the potential use and challenges associated with the use of aptamers alone or aptamer–ncRNA conjugates, nanoparticles, and multivalent aptamer-based therapeutics for the treatment of OC. Full article
(This article belongs to the Special Issue Aptamers and Cancer)
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33 pages, 3086 KiB  
Review
Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches
by Tanja Jesenko, Simona Kranjc Brezar, Maja Cemazar, Alice Biasin, Domenico Tierno, Bruna Scaggiante, Mario Grassi, Chiara Grassi, Barbara Dapas, Nhung Hai Truong, Michela Abrami, Fabrizio Zanconati, Deborah Bonazza, Flavio Rizzolio, Salvatore Parisi, Giorgia Pastorin and Gabriele Grassi
Pharmaceutics 2023, 15(4), 1249; https://doi.org/10.3390/pharmaceutics15041249 - 15 Apr 2023
Cited by 6 | Viewed by 2594
Abstract
Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. [...] Read more.
Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. In this regard, two approaches can be considered: (1) the identification of tumor-targeted delivery systems and (2) the targeting of molecule(s) whose aberrant expression is confined to tumor cells. In this work, we focused on the second approach. Among the different kinds of possible target molecules, we discuss the potential therapeutic value of targeting non-coding RNAs (ncRNAs), which include micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules represent the most significant RNA transcripts in cells and can regulate many HCC features, including proliferation, apoptosis, invasion and metastasis. In the first part of the review, the main characteristics of HCC and ncRNAs are described. The involvement of ncRNAs in HCC is then presented over five sections: (a) miRNAs, (b) lncRNAs, (c) circRNAs, (d) ncRNAs and drug resistance and (e) ncRNAs and liver fibrosis. Overall, this work provides the reader with the most recent state-of-the-art approaches in this field, highlighting key trends and opportunities for more advanced and efficacious HCC treatments. Full article
(This article belongs to the Section Drug Targeting and Design)
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17 pages, 1601 KiB  
Review
Noncoding RNAs Emerging as Drugs or Drug Targets: Their Chemical Modification, Bio-Conjugation and Intracellular Regulation
by Jin Wang, Tian Tian, Xin Li and Yan Zhang
Molecules 2022, 27(19), 6717; https://doi.org/10.3390/molecules27196717 - 9 Oct 2022
Cited by 11 | Viewed by 3372
Abstract
With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as [...] Read more.
With the increasing understanding of various disease-related noncoding RNAs, ncRNAs are emerging as novel drugs and drug targets. Nucleic acid drugs based on different types of noncoding RNAs have been designed and tested. Chemical modification has been applied to noncoding RNAs such as siRNA or miRNA to increase the resistance to degradation with minimum influence on their biological function. Chemical biological methods have also been developed to regulate relevant noncoding RNAs in the occurrence of various diseases. New strategies such as designing ribonuclease targeting chimeras to degrade endogenous noncoding RNAs are emerging as promising approaches to regulate gene expressions, serving as next-generation drugs. This review summarized the current state of noncoding RNA-based theranostics, major chemical modifications of noncoding RNAs to develop nucleic acid drugs, conjugation of RNA with different functional biomolecules as well as design and screening of potential molecules to regulate the expression or activity of endogenous noncoding RNAs for drug development. Finally, strategies of improving the delivery of noncoding RNAs are discussed. Full article
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23 pages, 2748 KiB  
Review
Fluorescent Platforms for RNA Chemical Biology Research
by Jinxi Du, Ricky Dartawan, William Rice, Forrest Gao, Joseph H. Zhou and Jia Sheng
Genes 2022, 13(8), 1348; https://doi.org/10.3390/genes13081348 - 27 Jul 2022
Cited by 7 | Viewed by 4106
Abstract
Efficient detection and observation of dynamic RNA changes remain a tremendous challenge. However, the continuous development of fluorescence applications in recent years enhances the efficacy of RNA imaging. Here we summarize some of these developments from different aspects. For example, single-molecule fluorescence in [...] Read more.
Efficient detection and observation of dynamic RNA changes remain a tremendous challenge. However, the continuous development of fluorescence applications in recent years enhances the efficacy of RNA imaging. Here we summarize some of these developments from different aspects. For example, single-molecule fluorescence in situ hybridization (smFISH) can detect low abundance RNA at the subcellular level. A relatively new aptamer, Mango, is widely applied to label and track RNA activities in living cells. Molecular beacons (MBs) are valid for quantifying both endogenous and exogenous mRNA and microRNA (miRNA). Covalent binding enzyme labeling fluorescent group with RNA of interest (ROI) partially overcomes the RNA length limitation associated with oligonucleotide synthesis. Forced intercalation (FIT) probes are resistant to nuclease degradation upon binding to target RNA and are used to visualize mRNA and messenger ribonucleoprotein (mRNP) activities. We also summarize the importance of some fluorescence spectroscopic techniques in exploring the function and movement of RNA. Single-molecule fluorescence resonance energy transfer (smFRET) has been employed to investigate the dynamic changes of biomolecules by covalently linking biotin to RNA, and a focus on dye selection increases FRET efficiency. Furthermore, the applications of fluorescence assays in drug discovery and drug delivery have been discussed. Fluorescence imaging can also combine with RNA nanotechnology to target tumors. The invention of novel antibacterial drugs targeting non-coding RNAs (ncRNAs) is also possible with steady-state fluorescence-monitored ligand-binding assay and the T-box riboswitch fluorescence anisotropy assay. More recently, COVID-19 tests using fluorescent clustered regularly interspaced short palindromic repeat (CRISPR) technology have been demonstrated to be efficient and clinically useful. In summary, fluorescence assays have significant applications in both fundamental and clinical research and will facilitate the process of RNA-targeted new drug discovery, therefore deserving further development and updating. Full article
(This article belongs to the Special Issue RNA Chemical Biology)
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25 pages, 822 KiB  
Review
Non-Coding RNAs in the Therapeutic Landscape of Pathological Cardiac Hypertrophy
by Joana Silva and Paula A. da Costa Martins
Cells 2022, 11(11), 1805; https://doi.org/10.3390/cells11111805 - 31 May 2022
Cited by 4 | Viewed by 4112
Abstract
Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the [...] Read more.
Cardiovascular diseases are a major health problem, and long-term survival for people diagnosed with heart failure is, still, unrealistic. Pathological cardiac hypertrophy largely contributes to morbidity and mortality, as effective therapeutic approaches are lacking. Non-coding RNAs (ncRNAs) arise as active regulators of the signaling pathways and mechanisms that govern this pathology, and their therapeutic potential has received great attention in the last decades. Preclinical studies in large animal models have been successful in ameliorating cardiac hypertrophy, and an antisense drug for the treatment of heart failure has, already, entered clinical trials. In this review, we provide an overview of the molecular mechanisms underlying cardiac hypertrophy, the involvement of ncRNAs, and the current therapeutic landscape of oligonucleotides targeting these regulators. Strategies to improve the delivery of such therapeutics and overcome the actual challenges are, also, defined and discussed. With the fast advance in the improvement of oligonucleotide drug delivery, the inclusion of ncRNAs-targeting therapies for cardiac hypertrophy seems, increasingly, a closer reality. Full article
(This article belongs to the Special Issue Cellular Signaling Leading to Heart Failure)
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15 pages, 6678 KiB  
Review
ncRNAs in Therapeutics: Challenges and Limitations in Nucleic Acid-Based Drug Delivery
by Miguel Hueso, Adrián Mallén, Marc Suñé-Pou, Josep M. Aran, Josep M. Suñé-Negre and Estanislao Navarro
Int. J. Mol. Sci. 2021, 22(21), 11596; https://doi.org/10.3390/ijms222111596 - 27 Oct 2021
Cited by 40 | Viewed by 3956
Abstract
Non-coding RNAs (ncRNAs) are emerging therapeutic tools but there are barriers to their translation to clinical practice. Key issues concern the specificity of the targets, the delivery of the molecules, and their stability, while avoiding “on-target” and “off-target” side effects. In this “ncRNA [...] Read more.
Non-coding RNAs (ncRNAs) are emerging therapeutic tools but there are barriers to their translation to clinical practice. Key issues concern the specificity of the targets, the delivery of the molecules, and their stability, while avoiding “on-target” and “off-target” side effects. In this “ncRNA in therapeutics” issue, we collect several studies of the differential expression of ncRNAs in cardiovascular diseases, bone metabolism-related disorders, neurology, and oncology, and their potential to be used as biomarkers or therapeutic targets. Moreover, we review recent advances in the use of antisense ncRNAs in targeted therapies with a particular emphasis on their basic biological mechanisms, their translational potential, and future trends. Full article
(This article belongs to the Special Issue ncRNAS in Therapeutics)
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31 pages, 1894 KiB  
Review
Bioengineering of Extracellular Vesicles: Exosome-Based Next-Generation Therapeutic Strategy in Cancer
by Priyanka Saha, Suchisnigdha Datta, Sukanya Ghosh, Anurima Samanta, Paramita Ghosh and Dona Sinha
Bioengineering 2021, 8(10), 139; https://doi.org/10.3390/bioengineering8100139 - 10 Oct 2021
Cited by 5 | Viewed by 4798
Abstract
Extracellular nano vesicles and exosomes hold compelling evidence in intercellular communication. Exosomal intracellular signal transduction is mediated by the transfer of cargo proteins, lipids, micro (mi)RNAs, long noncoding (lnc)RNAs, small interfering (si)RNAs, DNA, and other functional molecules that play a pivotal role in [...] Read more.
Extracellular nano vesicles and exosomes hold compelling evidence in intercellular communication. Exosomal intracellular signal transduction is mediated by the transfer of cargo proteins, lipids, micro (mi)RNAs, long noncoding (lnc)RNAs, small interfering (si)RNAs, DNA, and other functional molecules that play a pivotal role in regulating tumor growth and metastasis. However, emerging research trends indicate that exosomes may be used as a promising tool in anticancer treatment. This review features a majority of the bioengineering applications of fabricated exosomal cargoes. It also encompasses how the manipulation and delivery of specific cargoes—noncoding RNAs (ncRNAs), recombinant proteins, immune-modulators, chemotherapeutic drugs, and other small molecules—may serve as a precise therapeutic approach in cancer management. Full article
(This article belongs to the Special Issue Extracellular Vesicles: From Biology to Biomedical Application)
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20 pages, 3059 KiB  
Review
MicroRNAs and Long Noncoding RNAs as Novel Therapeutic Targets in Estrogen Receptor-Positive Breast and Ovarian Cancers
by Tushar Singh Barwal, Uttam Sharma, Sonali Bazala, Ipsa Singh, Manju Jain, Hridayesh Prakash, Shashank Shekhar, Elise N. Sandberg, Anupam Bishayee and Aklank Jain
Int. J. Mol. Sci. 2021, 22(8), 4072; https://doi.org/10.3390/ijms22084072 - 15 Apr 2021
Cited by 13 | Viewed by 3857
Abstract
Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies [...] Read more.
Aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane have shown to prevent metastasis and angiogenesis in estrogen receptor (ER)-positive breast and ovarian tumors. They function primarily by reducing estrogen production in ER-positive post-menopausal breast and ovarian cancer patients. Unfortunately, current AI-based therapies often have detrimental side-effects, along with acquired resistance, with increased cancer recurrence. Thus, there is an urgent need to identify novel AIs with fewer side effects and improved therapeutic efficacies. In this regard, we and others have recently suggested noncoding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), as potential molecular targets for utilization in modulating cancer hallmarks and overcoming drug resistance in several cancers, including ER-positive breast and ovarian cancer. Herein, we describe the disruptive functions of several miRNAs and lncRNAs seen in dysregulated cancer metabolism, with a focus on the gene encoding for aromatase (CYP19A1 gene) and estrogen synthesis as a novel therapeutic approach for treating ER-positive breast and ovarian cancers. Furthermore, we discuss the oncogenic and tumor-suppressive roles of several miRNAs (oncogenic miRNAs: MIR125b, MIR155, MIR221/222, MIR128, MIR2052HG, and MIR224; tumor-suppressive miRNAs: Lethal-7f, MIR27B, MIR378, and MIR98) and an oncogenic lncRNA (MIR2052HG) in aromatase-dependent cancers via transcriptional regulation of the CYP19A1 gene. Additionally, we discuss the potential effects of dysregulated miRNAs and lncRNAs on the regulation of critical oncogenic molecules, such as signal transducer, and activator of transcription 3, β-catenin, and integrins. The overall goal of this review is to stimulate further research in this area and to facilitate the development of ncRNA-based approaches for more efficacious treatments of ER-positive breast and ovarian cancer patients, with a slight emphasis on associated treatment–delivery mechanisms. Full article
(This article belongs to the Special Issue Molecular Target and Action Mechanism of Anti-Cancer Agents)
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388 KiB  
Review
Exosomal Non-Coding RNAs: Diagnostic, Prognostic and Therapeutic Applications in Cancer
by Marc D. Bullock, Andreia M. Silva, Pinar Kanlikilicer-Unaldi, Justyna Filant, Mohammed H. Rashed, Anil K. Sood, Gabriel Lopez-Berestein and George A. Calin
Non-Coding RNA 2015, 1(1), 53-68; https://doi.org/10.3390/ncrna1010053 - 3 Jun 2015
Cited by 83 | Viewed by 10483
Abstract
Non-coding RNAs, such as microRNAs and long non-coding RNAs, are important regulatory molecules which are corrupted in cancer, often in a tissue and stage specific manner. Accumulated data suggests that these promising biomarkers, may also form the basis of novel targeted therapeutic strategies. [...] Read more.
Non-coding RNAs, such as microRNAs and long non-coding RNAs, are important regulatory molecules which are corrupted in cancer, often in a tissue and stage specific manner. Accumulated data suggests that these promising biomarkers, may also form the basis of novel targeted therapeutic strategies. The role of exosomes in cancer development and metastasis pathways is also increasingly well described. These endosome derived extracellular vesicles which are trafficked horizontally between tumor cells, and vertically between tumor cells and the surrounding microenvironment, carry bioactive cargos, which can reprogram the phenotype of recipient cells with important oncogenic consequences. Exosomes are enriched with non-coding RNA content. Within exosomes, non-coding RNAs are secreted into the peripheral circulation and other bodily fluids where they are protected from enzymatic degradation by the surrounding phospholipid membrane. Exosomes are therefore a highly promising source of diagnostic and prognostic material in cancer. Furthermore, as exosomes are natural ncRNA carriers, they may be adapted for the purpose of drug delivery by the introduction of exogenous ncRNAs or by manipulating their endogenous ncRNA content. In the current review, we will explore these highly clinically relevant themes by examining the roles of exosomal ncRNAs in cancer diagnostics, prognostics and therapy. Full article
(This article belongs to the Section Clinical Applications of Non-Coding RNA)
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