Antisense Oligonucleotides, A Novel Developing Targeting Therapy

Karaki, Sara; Paris, Clément; Rocchi, Palma

doi:10.5772/intechopen.82105

Cited by 30 publications

(34 citation statements)

References 72 publications

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“…ASOs are single DNA strands of around 20 nucleotides that specifically hybridize to the complementary sequence of the target RNA. Depending on the type of ASO, the resulting DNA:RNA hybrid can induce mRNA cleavage catalyzed by the host RNase H enzyme, alter splicing, or form a steric blockade to disrupt translation, thereby knocking down the expression of target proteins ( Karaki et al., 2019 ). To date, there are seven FDA-approved ASO therapies, including Vitraven (cytomegalovirus retinitis, 1998) and Exondys 51 (Duchenne muscular dystrophy, 2016) ( Stein and Castanotto, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting

et al. 2020

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The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.

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Section: Introductionmentioning

confidence: 99%

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting

et al. 2020

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“…ASOs are defined as short, synthetic, single-stranded oligodeoxynucleotides (usually 15-25 nucleotides in length) that can target transcripts through Watson-Crick hybridization [40]. The resulting DNA:RNA hybrids can lead to cellular RNase H recruitment and cleavage of the RNA in the heteroduplexes by RNase H [41,42]. Alternatively, ASOs can function in an RNase H-independent manner by disrupting translation of the targeted transcripts via steric hindrance or by modulating pre-mRNA alternative splicing through blocking splicing cis-elements and/or affecting RNA structure (known as splice switching oligonucleotides) [43,44] (Figure 2).…”

Section: Aso Technology Against Covsmentioning

confidence: 99%

Nucleic Acid-Based Technologies Targeting Coronaviruses

Paris

Khan

et al. 2021

Trends in Biochemical Sciences

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently creating a global health emergency. This crisis is driving a worldwide effort to develop effective vaccines, prophylactics, and therapeutics. Nucleic acid (NA)-based treatments hold great potential to combat outbreaks of coronaviruses (CoVs) due to their rapid development, high target specificity, and the capacity to increase druggability. Here, we review key anti-CoV NA-based technologies, including antisense oligonucleotides (ASOs), siRNAs, RNA-targeting clustered regularly interspaced short palindromic repeats-CRISPR-associated protein (CRISPR-Cas), and mRNA vaccines, and discuss improved delivery methods and combination therapies with other antiviral drugs. Coronaviruses and Nucleic Acid-Based TechnologiesCoronaviruses (CoVs) are positive-sense, single-stranded RNA (ssRNA) viruses from the Coronaviridae family in the order Nidovirales [1]. CoVs are organized into four main genera: Alpha-, Beta-, Gamma-, and Delta-coronaviruses. Many zoonotic (see Glossary) pathogenic CoVs belong to the Betacoronavirus genus, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 that is responsible for the current coronavirus disease 2019 (COVID-19) pandemic [2]. Other major zoonotic CoVs, such as the human coronaviruses (HCoVs), including HCoV-229E and HCoV-NL63 (in the Alphacoronavirus genus), and HCoV-OC43 and HCoV-HKU1 (in the Betacoronavirus genus), cause common colds in humans [3,4]. The polycistronic CoV RNA genome is approximately 30 kb long and encodes 14 open reading frames (ORFs). The 5′ proximal end of the genome contains two large ORFs that comprise two-thirds of the viral genome. These ORFs are translated into two large polyproteins that encode 16 nonstructural proteins (nsps) that are mainly involved in viral replication and transcription [5]. The remaining onethird of the viral genome encodes four major structural proteins: spike surface glycoprotein (S), membrane (M), nucleocapsid (N), envelope (E), and the accessory proteins, which are required for viral entry into the host cells and viral budding [6]. HighlightsNucleic-acid based therapies are worth developing against coronavirus (CoV) outbreaks because of their high specificity and rapid development.

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“…ASOs have been designed as potential therapies for various diseases, including AS, spinal muscular atrophy (SMA), Duchenne muscular dystrophy, Huntington disease, and hyperlipidemia ( Beaudet and Meng, 2016 ; Dhuri et al, 2020 ). Several ASO-based therapies, such as Nusinersen (Spinraza) for SMA treatment, have received approval by the United States Food and Drug Administration (FDA) and other regional regulatory agencies ( Karaki et al, 2019 ). Nusinersen is quite effective in rescuing protein deficiency by altering pre-mRNA splicing ( Hoy, 2017 ; Groen et al, 2018 ; Claborn et al, 2019 ).…”

Section: Modulation Of the Long Non-coding Rna Ube3a-ats To Rescue Abnormal Imprinting In Prader–willi Syndrome/angelmmentioning

confidence: 99%

The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets

Wang

Jianjian

Yang

et al. 2021

Front. Cell Dev. Biol.

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Genomic imprinting is a term used for an intergenerational epigenetic inheritance and involves a subset of genes expressed in a parent-of-origin-dependent way. Imprinted genes are expressed preferentially from either the paternally or maternally inherited allele. Long non-coding RNAs play essential roles in regulating this allele-specific expression. In several well-studied imprinting clusters, long non-coding RNAs have been found to be essential in regulating temporal- and spatial-specific establishment and maintenance of imprinting patterns. Furthermore, recent insights into the epigenetic pathological mechanisms underlying human genomic imprinting disorders suggest that allele-specific expressed imprinted long non-coding RNAs serve as an upstream regulator of the expression of other protein-coding or non-coding imprinted genes in the same cluster. Aberrantly expressed long non-coding RNAs result in bi-allelic expression or silencing of neighboring imprinted genes. Here, we review the emerging roles of long non-coding RNAs in regulating the expression of imprinted genes, especially in human imprinting disorders, and discuss three strategies targeting the central long non-coding RNA UBE3A-ATS for the purpose of developing therapies for the imprinting disorders Prader–Willi syndrome and Angelman syndrome. In summary, a better understanding of long non-coding RNA-related mechanisms is key to the development of potential therapeutic targets for human imprinting disorders.

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Antisense Oligonucleotides, A Novel Developing Targeting Therapy

Cited by 30 publications

References 72 publications

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting

Coronavirus RNA Proofreading: Molecular Basis and Therapeutic Targeting

Nucleic Acid-Based Technologies Targeting Coronaviruses

The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets

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