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Artigos de revistas sobre o tema "RNA-Targeted small molecules"

Autor: Grafiati

Publicado: 20 de julho de 2024

Última modificação: 31 de julho de 2025

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1

Chen, Shi-Jie, and Yuanzhe Zhou. "Harnessing Computational Approaches for RNA-Targeted Drug Discovery." RNA NanoMed 1, no. 1 (2024): 1–15. https://doi.org/10.59566/isrnn.2024.0101001.

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RNA molecules have emerged as promising therapeutic targets due to their diverse functional and regulatory roles within cells. Computational modeling in RNA-targeted drug discovery presents a significant opportunity to expedite the discovery of novel small molecule compounds. However, this field encounters unique challenges compared to protein-targeted drug design, primarily due to limited experimental data availability and current models’ inability to adequately address RNA’s conformational flexibility during ligand recognition. Despite these challenges, several studies have successfully iden

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Xu, Ling, Kevin Chung, Tianshuo Liu, and Anna Marie Pyle. "Structural insights into RNA targeting with de novo small molecule." Structural Dynamics 12, no. 2_Supplement (2025): A41. https://doi.org/10.1063/4.0000350.

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Targeting RNA with small molecules has emerged as a promising approach in drug development, offering the potential to expand the druggable genome and enable pharmacological targeting of non-coding genes or difficult-to-target gene products. However, the identification of functionally active RNA binders faces low hit rates in routine chemical space exploration and lacks robust high-throughput screening assays. The visualization of atomic details of RNA-small molecule interactions also poses a challenge due to the dynamic nature of RNA molecules. To address these challenges, we targeted a struct

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3

Costales, Matthew G., Haruo Aikawa, Yue Li, et al. "Small-molecule targeted recruitment of a nuclease to cleave an oncogenic RNA in a mouse model of metastatic cancer." Proceedings of the National Academy of Sciences 117, no. 5 (2020): 2406–11. http://dx.doi.org/10.1073/pnas.1914286117.

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As the area of small molecules interacting with RNA advances, general routes to provide bioactive compounds are needed as ligands can bind RNA avidly to sites that will not affect function. Small-molecule targeted RNA degradation will thus provide a general route to affect RNA biology. A non–oligonucleotide-containing compound was designed from sequence to target the precursor to oncogenic microRNA-21 (pre–miR-21) for enzymatic destruction with selectivity that can exceed that for protein-targeted medicines. The compound specifically binds the target and contains a heterocycle that recruits an

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4

Nagano, Konami, Takashi Kamimura, and Gota Kawai. "Interaction between a fluoroquinolone derivative and RNAs with a single bulge." Journal of Biochemistry 171, no. 2 (2021): 239–44. http://dx.doi.org/10.1093/jb/mvab124.

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Abstract Interaction analysis between small molecules and RNA as well as structure determination of RNA–small molecule complexes will be the clues to search for compounds that bind to specific mRNA or non-coding RNA in drug discovery. In this study, the RNA-binding ability of a fluoroquinolone derivative, KG022, was examined against single-residue bulge-containing hairpin RNAs as RNA models. Nuclear magnetic resonance analysis indicated that KG022 interacts with the RNAs in the vicinity of the bulge residue, with preferring C and G as the bulge residues. The solution structures of the RNA–KG02

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5

Sun, Saisai, Jianyi Yang, and Zhaolei Zhang. "RNALigands: a database and web server for RNA–ligand interactions." RNA 28, no. 2 (2021): 115–22. http://dx.doi.org/10.1261/rna.078889.121.

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RNA molecules can fold into complex and stable 3D structures, allowing them to carry out important genetic, structural, and regulatory roles inside the cell. These complex structures often contain 3D pockets made up of secondary structural motifs that can be potentially targeted by small molecule ligands. Indeed, many RNA structures in PDB contain bound small molecules, and high-throughput experimental studies have generated a large number of interacting RNA and ligand pairs. There is considerable interest in developing small molecule lead compounds targeting viral RNAs or those RNAs implicate

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6

Tadesse, Kisanet, and Raphael I. Benhamou. "Targeting MicroRNAs with Small Molecules." Non-Coding RNA 10, no. 2 (2024): 17. http://dx.doi.org/10.3390/ncrna10020017.

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MicroRNAs (miRs) have been implicated in numerous diseases, presenting an attractive target for the development of novel therapeutics. The various regulatory roles of miRs in cellular processes underscore the need for precise strategies. Recent advances in RNA research offer hope by enabling the identification of small molecules capable of selectively targeting specific disease-associated miRs. This understanding paves the way for developing small molecules that can modulate the activity of disease-associated miRs. Herein, we discuss the progress made in the field of drug discovery processes,

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7

Angelbello, Alicia J., Suzanne G. Rzuczek, Kendra K. Mckee, et al. "Precise small-molecule cleavage of an r(CUG) repeat expansion in a myotonic dystrophy mouse model." Proceedings of the National Academy of Sciences 116, no. 16 (2019): 7799–804. http://dx.doi.org/10.1073/pnas.1901484116.

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Myotonic dystrophy type 1 (DM1) is an incurable neuromuscular disorder caused by an expanded CTG repeat that is transcribed into r(CUG)exp. The RNA repeat expansion sequesters regulatory proteins such as Muscleblind-like protein 1 (MBNL1), which causes pre-mRNA splicing defects. The disease-causing r(CUG)exp has been targeted by antisense oligonucleotides, CRISPR-based approaches, and RNA-targeting small molecules. Herein, we describe a designer small molecule, Cugamycin, that recognizes the structure of r(CUG)exp and cleaves it in both DM1 patient-derived myotubes and a DM1 mouse model, leavi

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Wu, Liping, Jing Pan, Vala Thoroddsen, et al. "Novel Small-Molecule Inhibitors of RNA Polymerase III." Eukaryotic Cell 2, no. 2 (2003): 256–64. http://dx.doi.org/10.1128/ec.2.2.256-264.2003.

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ABSTRACT A genetic approach utilizing the yeast Saccharomyces cerevisiae was used to identify the target of antifungal compounds. This analysis led to the identification of small molecule inhibitors of RNA polymerase (Pol) III from Saccharomyces cerevisiae. Three lines of evidence show that UK-118005 inhibits cell growth by targeting RNA Pol III in yeast. First, a dominant mutation in the g domain of Rpo31p, the largest subunit of RNA Pol III, confers resistance to the compound. Second, UK-118005 rapidly inhibits tRNA synthesis in wild-type cells but not in UK-118005 resistant mutants. Third,

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Alagia, Adele, Jana Tereňová, Ruth F. Ketley, Arianna Di Fazio, Irina Chelysheva, and Monika Gullerova. "Small vault RNA1-2 modulates expression of cell membrane proteins through nascent RNA silencing." Life Science Alliance 6, no. 6 (2023): e202302054. http://dx.doi.org/10.26508/lsa.202302054.

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Gene expression can be regulated by transcriptional or post-transcriptional gene silencing. Recently, we described nuclear nascent RNA silencing that is mediated by Dicer-dependent tRNA-derived small RNA molecules. In addition to tRNA, RNA polymerase III also transcribes vault RNA, a component of the ribonucleoprotein complex vault. Here, we show that Dicer-dependent small vault RNA1-2 (svtRNA1-2) associates with Argonaute 2 (Ago2). Although endogenous vtRNA1-2 is present mostly in the cytoplasm, svtRNA1-2 localises predominantly in the nucleus. Furthermore, in Ago2 and Dicer knockdown cells,

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10

Francois-Moutal, Liberty, David Donald Scott, and May Khanna. "Direct targeting of TDP-43, from small molecules to biologics: the therapeutic landscape." RSC Chemical Biology 2, no. 4 (2021): 1158–66. http://dx.doi.org/10.1039/d1cb00110h.

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Given the therapeutic interest of targeting TDP-43, this review focuses on the current landscape of strategies, ranging from biologics to small molecules, that directly target TDP-43. Regions targeted are shown on the 3D structure of RNA-bound TDP-43.

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Smola, Matthew J., Krista Marran, Sarah E. Thompson, et al. "Abstract 680: Leveraging an RNA-targeting platform for the discovery of cell-active c-MYC mRNA-binding small molecules." Cancer Research 84, no. 6_Supplement (2024): 680. http://dx.doi.org/10.1158/1538-7445.am2024-680.

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Abstract The MYC gene, with its oncogenic potential, has long been a formidable challenge in conventional drug discovery efforts, and its critical role in cancer progression and resistance has underscored the need for innovative therapeutic strategies. Here we demonstrate the capabilities of the Ribometrix RNA-targeting platform to modulate the c-MYC mRNA with small molecules with the aim of reducing c-MYC protein levels. Using our comprehensive platform of RNA-targeting drug discovery tools and analyses including chemical probing, structure modeling, high-purity RNA production, high-throughpu

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12

Nadir, Khan1 Farzeen Shaba2 Abu Sehma3 Mohd Faizan4 Rumana Siddqui5 Dr. Mohd Abid6*. "A Comprehensive Review About Exploring the Functional Diversity, Structural Complexity, And Interconnectivity of RNA Molecules: Implications for Gene Regulation, Cellular Processes, And Therapeutic Innovations." International Journal of Pharmaceutical Sciences 3, no. 5 (2025): 2171–80. https://doi.org/10.5281/zenodo.15398199.

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RNA (ribonucleic acid) is a versatile biomolecule that plays fundamental roles in gene expression, protein synthesis, and cellular regulation. Beyond its well-known functions in transcription and translation, RNA participates in various regulatory and structural processes essential for maintaining cellular homeostasis. This review explores the diversity of RNA molecules, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and non-coding RNAs such as small nuclear RNA (snRNA), microRNA (miRNA), small interfering RNA (siRNA), long non-coding RNA (lncRNA), circular RNA (cir

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13

Martín-Villamil, María, Isaías Sanmartín, Ángela Moreno, and José Gallego. "Pharmacophore-Based Discovery of Viral RNA Conformational Modulators." Pharmaceuticals 15, no. 6 (2022): 748. http://dx.doi.org/10.3390/ph15060748.

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New RNA-binding small-molecule scaffolds are needed to unleash the pharmacological potential of RNA targets. Here we have applied a pharmacophore-based virtual screening approach, seldom used in the RNA recognition field, to identify novel conformational inhibitors of the hepatitis C virus internal ribosome entry site. The conformational effect of the screening hits was assessed with a fluorescence resonance energy transfer assay, and the affinity, specificity, and binding site of the ligands were determined using a combination of fluorescence intensity and NMR spectroscopy experiments. The re

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14

Mirón-Barroso, Sofía, Joana S. Correia, Adam E. Frampton, et al. "Polymeric Carriers for Delivery of RNA Cancer Therapeutics." Non-Coding RNA 8, no. 4 (2022): 58. http://dx.doi.org/10.3390/ncrna8040058.

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As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has ‘druggable’ active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be

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15

Hardigan, Andrew A., Brian S. Roberts, Dianna E. Moore, Ryne C. Ramaker, Angela L. Jones, and Richard M. Myers. "CRISPR/Cas9-targeted removal of unwanted sequences from small-RNA sequencing libraries." Nucleic Acids Research 47, no. 14 (2019): e84-e84. http://dx.doi.org/10.1093/nar/gkz425.

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Abstract In small RNA (smRNA) sequencing studies, highly abundant molecules such as adapter dimer products and tissue-specific microRNAs (miRNAs) inhibit accurate quantification of lowly expressed species. We previously developed a method to selectively deplete highly abundant miRNAs. However, this method does not deplete adapter dimer ligation products that, unless removed by gel-separation, comprise most of the library. Here, we have adapted and modified recently described methods for CRISPR/Cas9–based Depletion of Abundant Species by Hybridization (‘DASH’) to smRNA-seq, which we have termed

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16

Tran, Anh Thi-Phuong, Duc Huy Vo, Audrey Di Giorgio, and Maria Duca. "ID: 1083 Targeting the production of oncogenic miRNAs using synthetic small molecules." Biomedical Research and Therapy 4, S (2017): 170. http://dx.doi.org/10.15419/bmrat.v4is.357.

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MicroRNAs (miRNAs or miRs) are a class of evolutionary conserved small non-coding RNAs that act as post-transcriptional regulators of gene expression. A wide number of studies has shown that the aberrant expression of miRNAs could be responsible for initiation and development of human cancers. Most of these deregulated miRNAs are overexpressed, thus being oncogenic. For these reasons, the inhibition of oncogenic miRNAs function or production would be a very promising approach for the development of new anticancer therapies [1]. The purpose of this work is the discovery of small-molecule

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17

Akbar, Sehrish, Yao Wei, and Mu-Qing Zhang. "RNA Interference: Promising Approach to Combat Plant Viruses." International Journal of Molecular Sciences 23, no. 10 (2022): 5312. http://dx.doi.org/10.3390/ijms23105312.

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Plant viruses are devastating plant pathogens that severely affect crop yield and quality. Plants have developed multiple lines of defense systems to combat viral infection. Gene silencing/RNA interference is the key defense system in plants that inhibits the virulence and multiplication of pathogens. The general mechanism of RNAi involves (i) the transcription and cleavage of dsRNA into small RNA molecules, such as microRNA (miRNA), or small interfering RNA (siRNA), (ii) the loading of siRNA/miRNA into an RNA Induced Silencing Complex (RISC), (iii) complementary base pairing between siRNA/miR

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18

Palazzotti, Deborah, Martina Sguilla, Giuseppe Manfroni, Violetta Cecchetti, Andrea Astolfi, and Maria Letizia Barreca. "Small Molecule Drugs Targeting Viral Polymerases." Pharmaceuticals 17, no. 5 (2024): 661. http://dx.doi.org/10.3390/ph17050661.

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Small molecules that specifically target viral polymerases—crucial enzymes governing viral genome transcription and replication—play a pivotal role in combating viral infections. Presently, approved polymerase inhibitors cover nine human viruses, spanning both DNA and RNA viruses. This review provides a comprehensive analysis of these licensed drugs, encompassing nucleoside/nucleotide inhibitors (NIs), non-nucleoside inhibitors (NNIs), and mutagenic agents. For each compound, we describe the specific targeted virus and related polymerase enzyme, the mechanism of action, and the relevant bioact

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19

Liu, Yuan, Mads B. Larsen, Bo Lin, et al. "Abstract 1805: Identification of a small molecule that induces targeted protein degradation of ADAR1." Cancer Research 83, no. 7_Supplement (2023): 1805. http://dx.doi.org/10.1158/1538-7445.am2023-1805.

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Abstract Adenosine deaminase acting on RNA (ADAR) are a family of enzymes that catalyzes the posttranscriptional conversion of adenosine to inosine in double-stranded RNA (dsRNA). Recent evidence suggests that genetic deletion of ADAR1 render tumors cells substantially more vulnerable to immunotherapy. In cells, ADAR1 is expressed as two different isoforms, the constitutively expressed ADAR1p110 and the inducible ADAR1p150. Evidence suggests that ADAR1p150 is the isoform that confers oncogenic and immune modulating effects in most tumors. Of note, many of the effects of ADAR1p150 appear to be

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20

Ruzi, Zukela, Daxiong Han, and Kailibinuer Aierken. "Advanced strategies for screening and identifying RNA-targeted small molecules: Bridging therapeutic potential and innovation." Results in Chemistry 15 (May 2025): 102305. https://doi.org/10.1016/j.rechem.2025.102305.

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21

Weller, Céline N., and Jonathan Hall. "Oligonucleotide-based PROTACs to Degrade RNA- and DNA-Binding Proteins." CHIMIA 79, no. 3 (2025): 167–71. https://doi.org/10.2533/chimia.2025.167.

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Proteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that sequester the endogenous protein degradation machinery of cells to induce degradation of targeted proteins. By bringing a target protein and a ubiquitin E3 ligase into close proximity, ubiquitin monomers can be transferred onto surface lysines of the protein, which is subsequently degraded by the proteasome. The functions of RNA- and DNA-binding proteins have been especially hard to modulate with small molecules. However, oligonucleotides that bind RNA- or DNA-binding proteins can be turned into oligonucleotide-base

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22

Cotten, M., G. Schaffner, and M. L. Birnstiel. "Ribozyme, antisense RNA, and antisense DNA inhibition of U7 small nuclear ribonucleoprotein-mediated histone pre-mRNA processing in vitro." Molecular and Cellular Biology 9, no. 10 (1989): 4479–87. http://dx.doi.org/10.1128/mcb.9.10.4479-4487.1989.

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A comparative analysis of ribozyme, antisense RNA, and antisense DNA inhibitors of the in vitro small nuclear ribonucleoprotein U7-dependent histone pre-mRNA processing reaction was performed. RNA molecules complementary to the U7 sequence inhibited in vitro processing of histone pre-mRNA at a sixfold excess over U7. Single-stranded DNA complementary to the entire U7 sequence inhibited the reaction at a 60-fold excess over U7, while a short, 18-nucleotide DNA molecule complementary to the 5' end of U7 inhibited the processing reaction at a 600-fold excess. A targeted ribozyme was capable of sp

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Cotten, M., G. Schaffner, and M. L. Birnstiel. "Ribozyme, antisense RNA, and antisense DNA inhibition of U7 small nuclear ribonucleoprotein-mediated histone pre-mRNA processing in vitro." Molecular and Cellular Biology 9, no. 10 (1989): 4479–87. http://dx.doi.org/10.1128/mcb.9.10.4479.

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A comparative analysis of ribozyme, antisense RNA, and antisense DNA inhibitors of the in vitro small nuclear ribonucleoprotein U7-dependent histone pre-mRNA processing reaction was performed. RNA molecules complementary to the U7 sequence inhibited in vitro processing of histone pre-mRNA at a sixfold excess over U7. Single-stranded DNA complementary to the entire U7 sequence inhibited the reaction at a 60-fold excess over U7, while a short, 18-nucleotide DNA molecule complementary to the 5' end of U7 inhibited the processing reaction at a 600-fold excess. A targeted ribozyme was capable of sp

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24

Ala, Ugo. "Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story." Cells 9, no. 7 (2020): 1574. http://dx.doi.org/10.3390/cells9071574.

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MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are responsible for RNA silencing and post-transcriptional regulation of gene expression. They can mediate a fine-tuned crosstalk among coding and non-coding RNA molecules sharing miRNA response elements (MREs). In a suitable environment, both coding and non-coding RNA molecules can be targeted by the same miRNAs and can indirectly regulate each other by competing for them. These RNAs, otherwise known as competing endogenous RNAs (ceRNAs), lead to an additional post-transcriptional regulatory layer, where non-coding RNAs can find n

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25

Thaper, Daksh L., Ravi Munuganti, Shaghayegh Nouruzi, et al. "First-in-field small molecule inhibitors targeting BRN2 as a therapeutic strategy for small cell prostate cancer." Journal of Clinical Oncology 37, no. 7_suppl (2019): 260. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.260.

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260 Background: Resistance to newly developed androgen receptor pathway inhibitors (ARPIs), such as Enzalutamide (ENZ), rapidly emerges and patients generally die within two years. In particular, a subset of patients who relapse following ARPI therapy exhibit lineage switching whereby tumours shed their dependence on AR signaling and emerge with neuroendocrine features. These tumours, termed treatment induced neuroendocrine prostate cancer (t-NEPC), carry an extremely poor prognosis and, to date, treatment remains decades old cytotoxic chemotherapies; therefore, targeted therapies are desperat

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Rimoldi, O. J., B. Raghu, M. K. Nag, and G. L. Eliceiri. "Three new small nucleolar RNAs that are psoralen cross-linked in vivo to unique regions of pre-rRNA." Molecular and Cellular Biology 13, no. 7 (1993): 4382–90. http://dx.doi.org/10.1128/mcb.13.7.4382-4390.1993.

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We have recently described three novel human small nucleolar RNA species with unique nucleotide sequences, which were named E1, E2, and E3. The present article describes specific psoralen photocross-linking in whole HeLa cells of E1, E2, and E3 RNAs to nucleolar pre-rRNA. These small RNAs were cross-linked to different sections of pre-rRNA. E1 RNA was cross-linked to two segments of nucleolar pre-rRNA; one was within residues 697 to 1163 of the 5' external transcribed spacer, and the other one was between nucleotides 664 and 1021 of the 18S rRNA sequence. E2 RNA was cross-linked to a region wi

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Rimoldi, O. J., B. Raghu, M. K. Nag, and G. L. Eliceiri. "Three new small nucleolar RNAs that are psoralen cross-linked in vivo to unique regions of pre-rRNA." Molecular and Cellular Biology 13, no. 7 (1993): 4382–90. http://dx.doi.org/10.1128/mcb.13.7.4382.

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We have recently described three novel human small nucleolar RNA species with unique nucleotide sequences, which were named E1, E2, and E3. The present article describes specific psoralen photocross-linking in whole HeLa cells of E1, E2, and E3 RNAs to nucleolar pre-rRNA. These small RNAs were cross-linked to different sections of pre-rRNA. E1 RNA was cross-linked to two segments of nucleolar pre-rRNA; one was within residues 697 to 1163 of the 5' external transcribed spacer, and the other one was between nucleotides 664 and 1021 of the 18S rRNA sequence. E2 RNA was cross-linked to a region wi

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Tao, Wei, Arif Yurdagul, Na Kong та ін. "siRNA nanoparticles targeting CaMKIIγ in lesional macrophages improve atherosclerotic plaque stability in mice". Science Translational Medicine 12, № 553 (2020): eaay1063. http://dx.doi.org/10.1126/scitranslmed.aay1063.

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Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule—Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ). CaMKIIγ becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-t

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Fei, Yue, Tünde Nyikó, and Attila Molnar. "Non-perfectly matching small RNAs can induce stable and heritable epigenetic modifications and can be used as molecular markers to trace the origin and fate of silencing RNAs." Nucleic Acids Research 49, no. 4 (2021): 1900–1913. http://dx.doi.org/10.1093/nar/gkab023.

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Abstract Short non-coding RNA molecules (sRNAs) play a fundamental role in gene regulation and development in higher organisms. They act as molecular postcodes and guide AGO proteins to target nucleic acids. In plants, sRNA-targeted mRNAs are degraded, reducing gene expression. In contrast, sRNA-targeted DNA sequences undergo cytosine methylation referred to as RNA-directed DNA methylation (RdDM). Cytosine methylation can suppress transcription, thus sRNAs are potent regulators of gene expression. sRNA-mediated RdDM is involved in genome stability through transposon silencing, mobile signallin

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Rojas-Cruz, Alexis Felipe, and Clara Isabel Bermúdez-Santana. "Computational Prediction of RNA–RNA Interactions between Small RNA Tracks from Betacoronavirus Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA." Viruses 15, no. 8 (2023): 1647. http://dx.doi.org/10.3390/v15081647.

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Whether RNA–RNA interactions of cytoplasmic RNA viruses, such as Betacoronavirus, might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been controversial. Even more, whether RNA–RNA interactions of wild animal viruses may act as virus-derived small RNAs is unknown. Here, we address these issues in four ways. First, we use conserved RNA structures undergoing negative selection in the genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating in different bat species, intermediate animals, and human hosts. Second, a systematic literature review was conducte

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Alonso-Valenteen, Felix, Sayuri Pacheco, Dustin Srinivas, et al. "HER3-targeted protein chimera forms endosomolytic capsomeres and self-assembles into stealth nucleocapsids for systemic tumor homing of RNA interference in vivo." Nucleic Acids Research 47, no. 21 (2019): 11020–43. http://dx.doi.org/10.1093/nar/gkz900.

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AbstractRNA interference represents a potent intervention for cancer treatment but requires a robust delivery agent for transporting gene-modulating molecules, such as small interfering RNAs (siRNAs). Although numerous molecular approaches for siRNA delivery are adequate in vitro, delivery to therapeutic targets in vivo is limited by payload integrity, cell targeting, efficient cell uptake, and membrane penetration. We constructed nonviral biomaterials to transport small nucleic acids to cell targets, including tumor cells, on the basis of the self-assembling and cell-penetrating activities of

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Goldberg, Zelanna, Christian Maine, Gabrielle P. Dailey, et al. "Abstract 6403: A self-replicating RNA precision medicine approach to overcoming resistance to endocrine therapy in ER+BC." Cancer Research 83, no. 7_Supplement (2023): 6403. http://dx.doi.org/10.1158/1538-7445.am2023-6403.

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Abstract Drug resistance remains the major driving factor behind the clinical failure of targeted therapeutics. Current oncology precision medicine approaches rely on targeting known acquired resistance mutations, such as EGFR T790M or ALK/ROS mutations in NSCLC with 2nd and 3rd generation molecules designed to overcome or prevent resistance. These next generation targeted therapeutic approaches have increasingly long and complex drug development timelines and burdensome toxicities from off target effects (e.g. wild-type receptor targeting) or drug-drug interactions (DDI). The toxicities limit

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Li, Quan, Yanan Wang, Zhihui Sun, Haiyang Li, and Huan Liu. "The Biosynthesis Process of Small RNA and Its Pivotal Roles in Plant Development." International Journal of Molecular Sciences 25, no. 14 (2024): 7680. http://dx.doi.org/10.3390/ijms25147680.

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In the realm of plant biology, small RNAs (sRNAs) are imperative in the orchestration of gene expression, playing pivotal roles across a spectrum of developmental sequences and responses to environmental stressors. The biosynthetic cascade of sRNAs is characterized by an elaborate network of enzymatic pathways that meticulously process double-stranded RNA (dsRNA) precursors into sRNA molecules, typically 20 to 30 nucleotides in length. These sRNAs, chiefly microRNAs (miRNAs) and small interfering RNAs (siRNAs), are integral in guiding the RNA-induced silencing complex (RISC) to selectively tar

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Servan de Almeida, Renata, Djénéba Keita, Geneviève Libeau, and Emmanuel Albina. "Control of ruminant morbillivirus replication by small interfering RNA." Journal of General Virology 88, no. 8 (2007): 2307–11. http://dx.doi.org/10.1099/vir.0.82981-0.

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Peste-des-petits-ruminants virus (PPRV) and rinderpest virus (RPV) are two morbilliviruses of economic relevance in African and Asian countries. Although efficient vaccines are available for both diseases, they cannot protect the animals before 14 days post-vaccination. In emergencies, it would be desirable to have efficient therapeutics for virus control. Here, two regions are described in the nucleocapsid genes of PPRV and RPV that can be targeted efficiently by synthetic short interfering RNAs (siRNAs), resulting in a >80 % reduction in virus replication. The effects of siRNAs on the pro

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Ashander, Liam M., Binoy Appukuttan, Yuefang Ma, Dione Gardner-Stephen, and Justine R. Smith. "Targeting Endothelial Adhesion Molecule Transcription for Treatment of Inflammatory Disease: A Proof-of-Concept Study." Mediators of Inflammation 2016 (2016): 1–8. http://dx.doi.org/10.1155/2016/7945848.

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Targeting the endothelial adhesion molecules that control leukocyte trafficking into a tissue has been explored as a biological therapy for inflammatory diseases. However, these molecules also participate in leukocyte migration for immune surveillance, and inhibiting the physiological level of an adhesion molecule might promote infection or malignancy. We explored the concept of targeting endothelial adhesion molecule transcription during inflammation in a human system. Intercellular adhesion molecule 1 (ICAM-1) mediates leukocyte migration across the retinal endothelium in noninfectious poste

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Lavender, Helen, Kevin Brady, Frances Burden, et al. "In VitroCharacterization of the Activity of PF-05095808, a Novel Biological Agent for Hepatitis C Virus Therapy." Antimicrobial Agents and Chemotherapy 56, no. 3 (2011): 1364–75. http://dx.doi.org/10.1128/aac.05357-11.

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ABSTRACTPF-05095808 is a novel biological agent for chronic hepatitis C virus (HCV) therapy. It comprises a recombinant adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of three short hairpin RNAs (shRNAs) targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence-specific cleavage of target regions. For small-molecule inhibitors the key screens needed to assessin vitroactivity are well defined; we developed new assays to assess this RNA interfer

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Hassanzadeh, Leila, Suxiang Chen, and Rakesh Veedu. "Radiolabeling of Nucleic Acid Aptamers for Highly Sensitive Disease-Specific Molecular Imaging." Pharmaceuticals 11, no. 4 (2018): 106. http://dx.doi.org/10.3390/ph11040106.

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Aptamers are short single-stranded DNA or RNA oligonucleotide ligand molecules with a unique three-dimensional shape, capable of binding to a defined molecular target with high affinity and specificity. Since their discovery, aptamers have been developed for various applications, including molecular imaging, particularly nuclear imaging that holds the highest potential for the clinical translation of aptamer-based molecular imaging probes. Their easy laboratory production without any batch-to-batch variations, their high stability, their small size with no immunogenicity and toxicity, and thei

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Madeha Maqsood, Saira Rehman, Rabia Akhtar, Zarkasha Rasheed, Tahseen ali khan, and Sidra Rao. "RNA Drug As Therapeutic Agents: A Review Based On Literature." Pakistan journal of Advances in Medicine and Medical Research 2, no. 01 (2024): 93–101. http://dx.doi.org/10.69837/pjammr.v2i01.28.

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Small RNA targeted drugs have received significant interest from the public and researches in the last decade due to their capability in treating different illnesses. RNA drugs corresponds to the small molecules which interact with and regulate the expression of particular genes at the level of RNA. Unlike ordinary small molecular chemicals, RNA drugs act directly on the nucleus and gene to produce very efficient and effective curative functions. Some of the RNA drugs are siRNA, ASOs, and mRNA, although the last one is used in vaccines. Both compounds, SiRNA and ASOs, act by attaching to the t

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Coll-SanMartin, Laia, Veronica Davalos, David Piñeyro, et al. "Gene Amplification-Associated Overexpression of the Selenoprotein tRNA Enzyme TRIT1 Confers Sensitivity to Arsenic Trioxide in Small-Cell Lung Cancer." Cancers 13, no. 8 (2021): 1869. http://dx.doi.org/10.3390/cancers13081869.

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The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced

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Hagiwara, Shinji, Aaron McClelland, and Phillip Kantharidis. "MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway." Journal of Diabetes Research 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/173783.

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MicroRNAs (miRNA) are a novel class of small, noncoding RNA molecules that have gained the attention of many researchers in recent years due to their ability to posttranscriptionally regulate the expression of families of genes simultaneously. Their role in normal physiology and pathobiology is intriguing and their regulation in normal and disease states is fascinating. That the cells can return to a state of homeostasis when these small molecules are perturbed is truly remarkable given the multiple cellular targets of each miRNA and that many mRNAs are targeted by multiple miRNAs. Several rev

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Cattaneo, Marco, Eleonora Giagnorio, Giuseppe Lauria, and Stefania Marcuzzo. "Therapeutic Approaches for C9ORF72-Related ALS: Current Strategies and Future Horizons." International Journal of Molecular Sciences 26, no. 13 (2025): 6268. https://doi.org/10.3390/ijms26136268.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. One of its major genetic causes is C9ORF72, where mutations lead to hexanucleotide repeat expansions in the C9ORF72 gene. These expansions drive disease progression through mechanisms, including the formation of toxic RNAs and the accumulation of damaged proteins such as dipeptide repeats (DPRs). This review highlights these pathogenic mechanisms, focusing on RNA foci formation and the accumulation of toxic DPRs, which contribute to neuronal damage. It also discu

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Liu, Runhan, Jiaxin Zhou, Xiaochen Chen, et al. "Diagnostic and Therapeutic Advances of RNAs in Precision Medicine of Gastrointestinal Tumors." Biomedicines 13, no. 1 (2024): 47. https://doi.org/10.3390/biomedicines13010047.

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Gastrointestinal tumors present a significant challenge for precision medicine due to their complexity, necessitating the development of more specific diagnostic tools and therapeutic agents. Recent advances have positioned coding and non-coding RNAs as emerging biomarkers for these malignancies, detectable by liquid biopsies, and as innovative therapeutic agents. Many RNA-based therapeutics, such as small interfering RNA (siRNA) and antisense oligonucleotides (ASO), have entered clinical trials or are available on the market. This review provides a narrative examination of the diagnostic and

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Kalynych, Sergei, Lenka Pálková, and Pavel Plevka. "The Structure of Human Parechovirus 1 Reveals an Association of the RNA Genome with the Capsid." Journal of Virology 90, no. 3 (2015): 1377–86. http://dx.doi.org/10.1128/jvi.02346-15.

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ABSTRACTParechoviruses are human pathogens that cause diseases ranging from gastrointestinal disorders to encephalitis. Unlike those of most picornaviruses, parechovirus capsids are composed of only three subunits: VP0, VP1, and VP3. Here, we present the structure of a human parechovirus 1 (HPeV-1) virion determined to a resolution of 3.1 Å. We found that interactions among pentamers in the HPeV-1 capsid are mediated by the N termini of VP0s, which correspond to the capsid protein VP4 and the N-terminal part of the capsid protein VP2 of other picornaviruses. In order to facilitate delivery of

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Tidwell, Elizabeth D., Ingrid R. Kilde, Suada Leskaj, and Markos Koutmos. "Fluorescent Ligand Equilibrium Displacement: A High-Throughput Method for Identification of FMN Riboswitch-Binding Small Molecules." International Journal of Molecular Sciences 25, no. 2 (2024): 735. http://dx.doi.org/10.3390/ijms25020735.

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Antibiotic resistance remains a pressing global concern, with most antibiotics targeting the bacterial ribosome or a limited range of proteins. One class of underexplored antibiotic targets is bacterial riboswitches, structured RNA elements that regulate key biosynthetic pathways by binding a specific ligand. We developed a methodology termed Fluorescent Ligand Equilibrium Displacement (FLED) to rapidly discover small molecules that bind the flavin mononucleotide (FMN) riboswitch. FLED leverages intrinsically fluorescent FMN and the quenching effect on RNA binding to create a label-free, in vi

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Xie, Zhengyang. "Applications and Challenges of RNA Interference Technology in Therapeutic Development." Theoretical and Natural Science 68, no. 1 (2025): 89–97. https://doi.org/10.54254/2753-8818/2025.19920.

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RNA interference (RNAi) is a potent biological mechanism enabling the targeted silencing of specific genes, transforming gene regulation and therapeutic approaches in medical science. Using small RNA molecules such as small interfering RNAs (siRNAs) and microRNAs (miRNAs), RNAi allows for precise mRNA degradation or translational repression. Clinically, RNAi has been applied to treat genetic disorders such as hereditary transthyretin amyloidosis (hATTR) and acute hepatic porphyria (AHP). RNAi also holds promise in cancer therapies, targeting oncogenes like KRAS and pathways such as PI3K/AKT/mT

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Simba-Lahuasi, Alvaro, Ángel Cantero-Camacho, Romel Rosales, et al. "SARS-CoV-2 Inhibitors Identified by Phenotypic Analysis of a Collection of Viral RNA-Binding Molecules." Pharmaceuticals 15, no. 12 (2022): 1448. http://dx.doi.org/10.3390/ph15121448.

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Antiviral agents are needed for the treatment of SARS-CoV-2 infections and to control other coronavirus outbreaks that may occur in the future. Here we report the identification and characterization of RNA-binding compounds that inhibit SARS-CoV-2 replication. The compounds were detected by screening a small library of antiviral compounds previously shown to bind HIV-1 or HCV RNA elements with a live-virus cellular assay detecting inhibition of SARS-CoV-2 replication. These experiments allowed detection of eight compounds with promising anti-SARS-CoV-2 activity in the sub-micromolar to micromo

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Kulbay, Merve, Nicolas Tuli, Arjin Akdag, Shigufa Kahn Ali, and Cynthia X. Qian. "Optogenetics and Targeted Gene Therapy for Retinal Diseases: Unravelling the Fundamentals, Applications, and Future Perspectives." Journal of Clinical Medicine 13, no. 14 (2024): 4224. http://dx.doi.org/10.3390/jcm13144224.

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With a common aim of restoring physiological function of defective cells, optogenetics and targeted gene therapies have shown great clinical potential and novelty in the branch of personalized medicine and inherited retinal diseases (IRDs). The basis of optogenetics aims to bypass defective photoreceptors by introducing opsins with light-sensing capabilities. In contrast, targeted gene therapies, such as methods based on CRISPR-Cas9 and RNA interference with noncoding RNAs (i.e., microRNA, small interfering RNA, short hairpin RNA), consists of inducing normal gene or protein expression into af

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Joshi, Mansi, Pranay Dey, and Abhijit De. "Recent advancements in targeted protein knockdown technologies—emerging paradigms for targeted therapy." Exploration of Targeted Anti-tumor Therapy 4, no. 6 (2023): 1227–48. http://dx.doi.org/10.37349/etat.2023.00194.

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A generalized therapeutic strategy for various disease conditions, including cancer, is to deplete or inactivate harmful protein targets. Various forms of protein or gene silencing molecules, e.g., small molecule inhibitors, RNA interference (RNAi), and microRNAs (miRNAs) have been used against druggable targets. Over the past few years, targeted protein degradation (TPD) approaches have been developed for direct degradation of candidate proteins. Among the TPD approaches, proteolysis targeting chimeras (PROTACs) have emerged as one of the most promising approaches for the selective eliminatio

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Mourenza, Álvaro, Blanca Lorente-Torres, Elena Durante, et al. "Understanding microRNAs in the Context of Infection to Find New Treatments against Human Bacterial Pathogens." Antibiotics 11, no. 3 (2022): 356. http://dx.doi.org/10.3390/antibiotics11030356.

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The development of RNA-based anti-infectives has gained interest with the successful application of mRNA-based vaccines. Small RNAs are molecules of RNA of <200 nucleotides in length that may control the expression of specific genes. Small RNAs include small interference RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), or microRNAs (miRNAs). Notably, the role of miRNAs on the post-transcriptional regulation of gene expression has been studied in detail in the context of cancer and many other genetic diseases. However, it is also becoming apparent that some human miRNAs possess important antim

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Harrington, Lucas B., David Burstein, Janice S. Chen, et al. "Programmed DNA destruction by miniature CRISPR-Cas14 enzymes." Science 362, no. 6416 (2018): 839–42. http://dx.doi.org/10.1126/science.aav4294.

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CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools use RNA-guided Cas proteins whose large size (950 to 1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400 to 700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequen

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