We should continue the half-century history of applications of antisense oligonucleotides in medicine, agriculture and forestry: a review

Oberemok, Volodymyr V.; Laikova, Kateryna V.; Repetskaya, Anna; Kenyo, Igor; Gorlov, Mikhail; Kasich, Igor; Krasnodubets, Alisa M.; Gal'chinsky, Nikita V; Фомочкина, И. И.; Zaitsev, A. A.; Bekirova, Viktoriya; Seidosmanova, E.; Dydik, Ksenia; Meshcheryakova, Anna; Назаров, С. А.; Smagliy, Natalya; Chelengerova, Edie; Kulanova, Alina; Deri, Karim; Subbotkin, Mikhail Vladimirovich; Useinov, Refat Z.; Shumskykh, Maksym N.; Kubyshkin, Anatoly V.

doi:10.20944/preprints201804.0366.v1

Cited by 12 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During this period, the methods for oligonucleotide synthesis and chemical modifications were also developed. [184][185][186] Single stranded antisense oligonucleotides (ASOs), messenger (m)RNAs and double stranded small-interfering RNAs (siRNAs) are the major classes of nucleic acids that currently dominate the clinical landscape.…”

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

“…ASOs inhibit gene-expression either by RNase-H-dependent mRNA degradation or by stearic hindrance that blocks access to essential enzymes. [186] The first application of synthetic ASOs was reported in the late 70s, [187] while the first ASO, Fomivirsen (Vitravene), was approved in 1998 for treating cytomegalovirusmediated retinitis in AIDS patients. [188] In the context of cancer, all ASOs evaluated in clinical trials are delivered as naked entities (Table S2, Supporting Information).…”

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

“…[192] In parallel, the existence of endogenous oligonucleotides that inhibit protein translation were first reported in 1977, [194] and later by several other groups. [186,195,196] Craig Melo and Andrew Fire received the 2006 Nobel Prize in Chemistry because of their discovery, in 1998, of the capacity of synthetic doublestranded RNA (dsRNA) to mediate gene-silencing. [195] This seminal work set-off the field of RNA interference (RNAi) and its potential for treating human diseases.…”

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

“…[211] So far, chemical modification of RNA has been the preferred approach for improving stability, potency, target specificity and reducing nonspecific immune activation. [186,199,211] The most common modifications used are 2′-fluoro, 2′-O-methyl, and phosphorothioate modifications for siRNA; [211] and phosphorothioate, O-methoxyethyl, constrained ethyl and locked nucleic acid modifications for ASOs. [186,189,190] As an extension to chemical modifications, RNA-ligand conjugates play an important role in the clinical development of RNA therapeutics, as the approval of Givosiran in 2019 and the positive phase III results of Inclisiran, both GalNAc-siRNA conjugates shows.…”

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

“…[186,199,211] The most common modifications used are 2′-fluoro, 2′-O-methyl, and phosphorothioate modifications for siRNA; [211] and phosphorothioate, O-methoxyethyl, constrained ethyl and locked nucleic acid modifications for ASOs. [186,189,190] As an extension to chemical modifications, RNA-ligand conjugates play an important role in the clinical development of RNA therapeutics, as the approval of Givosiran in 2019 and the positive phase III results of Inclisiran, both GalNAc-siRNA conjugates shows. [212] Having said that, nanotechnology has made important contributions in this field of nucleic acid delivery.…”

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

See 4 more Smart Citations

Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

Dacoba

Anthiya

Berrecoso

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

Research efforts towards cancer therapeutics have resulted in the development of a variety of pharmacological molecules, including small synthetic molecules and biological drugs (RNA-based therapies and monoclonal antibodies-mAbs), intended to target tumor or immune-related cells, or their signaling mediators. The majority of them present important biopharmaceutical problems related to their difficulties for overcoming biological barriers and reach their targets. Nanotechnology has been, for more than 60 years, trying to solve these problems. As knowledge in drug discovery, molecular biology, and biomaterials advances, there has been significant progress in the adequate design of nanodelivery strategies that may significantly contribute to the exploitation of the new therapies. This review provides a critical overview of the current potential of nanotechnology to solve problems associated with the different categories of drugs. Starting with the general concept of passive and active targeting, it presents the distinct advantages that delivery technologies have shown to date for improving the therapeutic outcome of small drugs with cytotoxic activity, RNA-and mAb-based therapies. Moreover, it precisely describes the benefits of combining immunotherapies and nanotechnology. The most advanced technologies are put into perspective in relation to their translational pathway and the future avenues for nano-oncologicals.

show abstract

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

Section: Emerging Nucleic Acids For Cancer Treatmentmentioning

confidence: 99%

See 3 more Smart Citations

Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

Dacoba

Anthiya

Berrecoso

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

show abstract

Absorption, Distribution, Metabolism, and Excretion of US Food and Drug Administration–Approved Antisense Oligonucleotide Drugs

Migliorati

Liu

et al. 2022

Drug Metab Dispos

View full text Add to dashboard Cite

Absorption, distribution, metabolism, and excretion (ADME) are the key biological processes for determination of a drug's pharmacokinetic parameters, which have direct impacts on efficacy and adverse drug reactions (ADRs). The chemical structures, dosage forms, and sites and routes of administration are the principal determinants of ADME profiles and consequent impacts on their efficacy and ADRs. Newly developed large biological antisense oligonucleotide (ASO) drugs have completely unique ADME that is not fully defined. ASO-based drugs are singlestranded synthetic antisense nucleic acids with diverse modes of drug actions from induction of mRNA degradation, exon skipping and restoration, and interactions with proteins. ASO drugs have a great potential to treat certain human diseases that have remained untreatable with small molecule-based drugs. The ADME of ASO drugs contributes to their unique set of ADRs and toxicity. In this review, to better understand their ADME, the ten FDA-approved ASO drugs were selected, including Fomivirsen, Pegaptanib, Mipomersen, Nusinersen, Inotersen, Defibrotide, Eteplirsen, Golodirsen, Viltolarsen, and Casimersen. A meta-analysis was conducted on their formulation, dosage, sites of administration, local and systematic distribution, metabolism, degradation, and excretion. Membrane permeabilization through endocytosis and nucleolytic degradation by endonucleases and exonucleases are major ADME features of the ASO drugs differing from small-molecule drugs. The information summarized here provides comprehensive ADME characteristics of FDA-approved ASO drugs, leading to a better understanding of their therapeutic efficacy and their potential ADRs and toxicity. Numerous knowledge gaps, particularly on cellular uptake and subcellular trafficking and distribution are identified, and future perspectives and directions are discussed.

show abstract

Casimersen (AMONDYS 45™): An Antisense Oligonucleotide for Duchenne Muscular Dystrophy

Assefa,

Gepfert,

Zaheer

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Casimersen (AMONDYS 45TM) is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer subclass developed by Sarepta therapeutics. It was approved by the Food and Drug Administration (FDA) in February 2021 to treat Duchenne muscular dystrophy (DMD) in patients whose DMD gene mutation is amenable to exon 45 skipping. Administered intravenously, casimersen binds to the pre-mRNA of the DMD gene to skip a mutated region of an exon, thereby producing an internally truncated yet functional dystrophin protein in DMD patients. This is essential in maintaining the structure of a myocyte membrane. While casimersen is currently continuing in phase III of clinical trials in various countries, it was granted approval by the FDA under the accelerated approval program due to its observed increase in dystrophin production. This article discusses the pathophysiology of DMD, summarizes available treatments thus far, and provides a full drug review of casimersen (AMONDYS 45TM).

show abstract

We should continue the half-century history of applications of antisense oligonucleotides in medicine, agriculture and forestry: a review

Cited by 12 publications

References 0 publications

Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

Nano‐Oncologicals: A Tortoise Trail Reaching New Avenues

Absorption, Distribution, Metabolism, and Excretion of US Food and Drug Administration–Approved Antisense Oligonucleotide Drugs

Casimersen (AMONDYS 45™): An Antisense Oligonucleotide for Duchenne Muscular Dystrophy

Contact Info

Product

Resources

About