Fomiversen Sodium Approved to Treat CMV Retinitis

Piascik, Peggy

doi:10.1016/s1086-5802(16)30428-4

Cited by 25 publications

(14 citation statements)

References 2 publications

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“…With the delivery to most organs mainly unsolved, there is so far no approved siRNA-based clinical treatment, 86 , 87 whereas two FDA-approved gapmers have reached the clinic for the treatment of CMV retinitis 88 and severe hypercholesterolaemia, respectively. 89 …”

Section: Aon S Inducing Rna Degradationmentioning

confidence: 99%

Oligonucleotide Therapies: The Past and the Present

2015

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In this review we address the development of oligonucleotide (ON) medicines from a historical perspective by listing the landmark discoveries in this field. The various biological processes that have been targeted and the corresponding ON interventions found in the literature are discussed together with brief updates on some of the more recent developments. Most ON therapies act through antisense mechanisms and are directed against various RNA species, as exemplified by gapmers, steric block ONs, antagomirs, small interfering RNAs (siRNAs), micro-RNA mimics, and splice switching ONs. However, ONs binding to Toll-like receptors and those forming aptamers have completely different modes of action. Similar to other novel medicines, the path to success has been lined with numerous failures, where different therapeutic ONs did not stand the test of time. Since the first ON drug was approved for clinical use in 1998, the therapeutic landscape has changed considerably, but many challenges remain until the expectations for this new form of medicine are met. However, there is room for cautious optimism.

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Section: Aon S Inducing Rna Degradationmentioning

confidence: 99%

Oligonucleotide Therapies: The Past and the Present

2015

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“…This backbone modification is present in a large proportion of the oligonucleotides in various phases of clinical trials. Additionally, the two oligonucleotides approved by the U.S. Food and Drug Administration as medicaments are fully phosphorothioated: Vitravene (Fomivirsen) for local delivery to the eye in 1998 [1,2], and Mipomersen (Kynamro) for systemic delivery in 2013 [3]. As background information, I will describe some of the chemical/biochemical properties of this particular nucleic acid modification to illustrate its differences from the phosphates.…”

Section: Introductionmentioning

confidence: 99%

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

Eckstein

2014

Nucleic Acid Therapeutics

526

385

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Phosphorothioates have found their usefulness in the general area of oligonucleotide therapeutic applications. Initially this modification was introduced into the antisense methodology because of the nuclease resistance of the phosphorothioate linkage in comparison with that of the phosphate linkage. However, as experimental data accumulated, it was detected that this chemical modification also facilitates cellular uptake and bioavailibity in vivo. Thus, today the majority of therapeutic oligonucleotides contain this modification. This review will discuss the historical development of this modification and present some of its chemical properties where they differ from those of the phosphate group. The antisense application will be discussed in the original context with cleavage of the target mRNA, but other target RNAs such as microRNAs and long noncoding RNAs will also be covered. It continues with applications where the target RNA should not be cleaved. A brief presentation of decoy oligonucleotides will be included, as well as some miscellaneous applications. Cellular uptake is a crucial step for oligonucleotides to reach their target and will be briefly reviewed. Lastly, a most surprising recent observation is the presence of phosphorothioate groups in bacterial DNA where functions still remain to be fully determined.

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“…From the last three decades, several antisense drugs have entered into clinical trials and market for the treatment of a broad variety of diseases, and numerous oligonucleotides are under clinical development [6,[8][9][10]. The firstgeneration antisense drug, fomivirsen, targeting cytomegalovirus, was approved for the treatment of cytomegalovirus retinitis [11]. Many second-generation drugs are under development and are showing encouraging activity in the clinic.…”

Section: Pharmacology Of Antisense Drugsmentioning

confidence: 99%

Antisense Therapy: An Overview

Sharad¹

2019

Antisense Therapy

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Nucleic acids are the backbone of antisense therapy. Antisense oligonucleotidebased therapeutics involves downregulation of gene expression. RNA-based drugs that include antisense oligonucleotides bear great therapeutic potential toward treatment of various diseases by altering RNA and/or reducing, restoring, and modifying protein expression through multiple molecular mechanisms. Pharmacology of targeted antisense therapy has provided the platform to translate its utility to the clinic. Over the years, chemical modifications of antisense oligonucleotides have not only enhanced the specificity and efficacy but also reduced the side effects. These have changed the whole clinical trial design and provide newer strategies for therapies. Improvement in antisense oligonucleotide therapy technology has allowed and brought research from bench to clinic. Additionally, the use of small interfering RNAs, micro RNAs, ribozymes, and other antisense compounds toward the treatment of deadly diseases like cancers have demonstrated both preclinical and clinical responses. Furthermore, antisense therapy has great potential to target specific genes of interest in the context of precision medicine. Optimization of enhanced delivery, specificity, affinity, and nuclease resistance with reduced toxicity is underway in different disease context. This chapter gives a complete overview of antisense therapy and highlights its potential. Here, we focused on the advances of the antisense technology, pharmacology, therapeutics, and drug discovery.

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Fomiversen Sodium Approved to Treat CMV Retinitis

Cited by 25 publications

References 2 publications

Oligonucleotide Therapies: The Past and the Present

Oligonucleotide Therapies: The Past and the Present

Phosphorothioates, Essential Components of Therapeutic Oligonucleotides

Antisense Therapy: An Overview

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