Journal ArticleDOI
Therapeutic targeting of microRNAs: current status and future challenges
Zhonghan Li,Tariq M. Rana +1 more
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TLDR
Current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides is summarized, various in vivo delivery strategies are discussed and ongoing challenges to ensure the specificity and efficacy of therapeutic oligon nucleotides in vivo are analysed.Abstract:
MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.read more
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MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
Journal ArticleDOI
Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.
TL;DR: In this review, state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies are discussed and the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting are emphasized.
Journal ArticleDOI
An overview of microRNAs
TL;DR: An overview of the miRNA pathway, including biogenesis routes, biological roles, and clinical approaches is presented, including clinical diagnostics and therapeutic targets.
Journal ArticleDOI
The chemical evolution of oligonucleotide therapies of clinical utility.
TL;DR: As oligonucleotides with a particular chemical design show appropriate distribution and safety profiles for clinical gene silencing in a particular tissue, this will open the door to the rapid development of additional drugs targeting other disease-associated genes in the same tissue.
Journal ArticleDOI
Non-coding RNAs as drug targets
Masayuki Matsui,David R. Corey +1 more
TL;DR: The growing field of ncRNA — including microRNA, intronic RNA, repetitive RNA and long non-coding RNA — is discussed and the potential and challenges in their therapeutic exploitation are assessed.
References
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MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
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MicroRNAs: Target Recognition and Regulatory Functions
TL;DR: The current understanding of miRNA target recognition in animals is outlined and the widespread impact of miRNAs on both the expression and evolution of protein-coding genes is discussed.
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Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Andrew Fire,SiQun Xu,Mary K. Montgomery,Steven A. Kostas,Steven A. Kostas,Samuel E. Driver,Craig C. Mello +6 more
TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
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The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
TL;DR: Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin- 4 regulates lin- 14 translation via an antisense RNA-RNA interaction.
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Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets
TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.