Locked Nucleic Acid Holds Promise in the Treatment of Cancer

Frieden, Miriam; Ørum, Henrik

doi:10.2174/138161208784246234

Cited by 46 publications

(38 citation statements)

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“…LNA-containing ODNs have been shown to be pharmacologically active in multiple tissues and species by multiple administration routes, with both mRNA and miRNA as the target. LNA drugs are under development for the treatment of cancer [50]. An LNA-modified oligonucleotide complementary to miR-122 has been shown to lead to long-lasting suppression of hepatitis C virus in chimpanzees [51] and is the first miRNA-targeting RNA drug to enter clinical trials.…”

Section: Bridged Nucleic Acidsmentioning

confidence: 99%

New Antisense Strategies: Chemical Synthesis of RNA Oligomers

Yano

Smyth

2011

Nucleic Acid Drugs

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In this chapter, we introduce our recent work on the development of new antisense strategies in RNA synthetic technology and RNA drug discovery. In the first part of the chapter, we briefly introduce selected chemical modifications of antisense oligomers and recent developments in antisense RNA. In the second part, we describe our research on RNA, including synthetic approaches to stereodefined backbone-modified oligoribonucleotides with chiral linkages, and the development of a method for the synthesis of RNA based on the use of 2-cyanoethoxymethyl (CEM) as the 2 0 -hydroxyl protecting group. The CEM method has been applied to the synthesis of single and double short hairpin RNA, pre-microRNA, and designed mRNA molecules up to 170 nucleotides in length, which were physicochemically identified and shown to be biologically active. We hope that the work presented here will contribute to the pushing forward of the frontiers of knowledge and understanding in RNA biology and RNA drug discovery.

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Section: Bridged Nucleic Acidsmentioning

confidence: 99%

New Antisense Strategies: Chemical Synthesis of RNA Oligomers

Yano

Smyth

2011

Nucleic Acid Drugs

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“…Currently there are preclinical trials and already the first clinical trials are examining antisense strategies directed against Bcl2,154 survivin and XIAP155 in various solid tumours.…”

Section: Induction Of Apoptosismentioning

confidence: 99%

Targeted treatments in colorectal cancer: state of the art and future perspectives

Arnold

Seufferlein

2010

Gut

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Targeted treatments have generated a lot of hope and hype in the treatment of gastrointestinal tumours. Indeed, the introduction of targeted treatments particularly for colorectal cancer has resulted in substantial improvements in tumour response and progression-free survival of patients. However, it is not fully understood how these agents act in patients, and the preclinical models are not appropriate to predict clinical efficacy. Here the current state of targeted treatments in colorectal cancer is reviewed, focusing on antiepidermal growth factor receptor (EGFR) and antiangiogenic strategies, describing how these agents fit into the therapeutic algorithm of this disease and discussing current understanding of the mechanism of action, biomarkers as well as future therapeutic strategies targeting multiple signalling pathways in colorectal cancer.

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“…LNAs comprise a class of bicyclic high-affinity RNA analogues in which the furanose ring of LNA monomers is conformationally locked in endo/N-type conformation. This modification is associated with a significantly reduced conformational flexibility and an increased local organization of the phosphate backbone (Frieden and Orum 2008;Kaur et al 2007).…”

Section: The Utility Of Locked Nucleic Acid (Lna) In Cns Researchmentioning

confidence: 99%

microRNAs in CNS Disorders

2009

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In recent years, there has been a shift in the conventional paradigms for transcriptional and translational regulation as extensive sequencing efforts have yielded new insights into the landscape of the human genome and transcriptome. Hundreds of non-coding regulatory RNA molecules called microRNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact the expression of numerous downstream mRNA targets. The intricate molecular networks mediated by an miRNA form a robust mechanism for rapid and potent responses to cellular events throughout the development of the human brain. Recent studies have identified a molecular and ultimately pathogenic role for a subset of miRNAs in Alzheimer's disease and schizophrenia, including the characterization of their downstream CNS mRNA targets, such as beta-secretase (BACE1) and calmodulin-dependent protein kinase II (CaMKII). Here, we present an overview of the current progress in miRNA research related to CNS disorders and also highlight the utility of LNA (locked nucleic acid)-modified oligonucleotides in the detection and modulation of miRNA activity.

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Locked Nucleic Acid Holds Promise in the Treatment of Cancer

Cited by 46 publications

References 0 publications

New Antisense Strategies: Chemical Synthesis of RNA Oligomers

New Antisense Strategies: Chemical Synthesis of RNA Oligomers

Targeted treatments in colorectal cancer: state of the art and future perspectives

microRNAs in CNS Disorders

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