Synthesis and biophysical properties of tetravalent PEG-conjugated antisense oligonucleotide

Chowdhury, Taslima Rahman; Taufiq, Tahia; Ishida, Kenta; Islam, Md Ariful; Kasahara, Yuuya; Osawa, Takashi; Obika, Satoshi

doi:10.1016/j.bmc.2022.117149

Cited by 2 publications

(3 citation statements)

References 33 publications

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“…Based on organic scaffolds, an interesting approach consists of linking multiple siRNAs or ASOs together, as a multimer vehicle to improve delivery ( Figure 4 B2) [ 83 , 84 ]. A Di-siRNA scaffold targeting SARS-Cov2 mRNA has been reported, showing interesting properties in terms of exposure and duration of the silencing effect in the lungs of mice, compared to the monovalent analogue [ 85 ].…”

Section: Delivery Platforms To Enhance Oligonucleotide Therapeutics I...mentioning

confidence: 99%

Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking

Mangla,

Vicentini,

Biscans

2023

Cells

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The potential of oligonucleotide therapeutics is undeniable as more than 15 drugs have been approved to treat various diseases in the liver, central nervous system (CNS), and muscles. However, achieving effective delivery of oligonucleotide therapeutics to specific tissues still remains a major challenge, limiting their widespread use. Chemical modifications play a crucial role to overcome biological barriers to enable efficient oligonucleotide delivery to the tissues/cells of interest. They provide oligonucleotide metabolic stability and confer favourable pharmacokinetic/pharmacodynamic properties. This review focuses on the various chemical approaches implicated in mitigating the delivery problem of oligonucleotides and their limitations. It highlights the importance of linkers in designing oligonucleotide conjugates and discusses their potential role in escaping the endosomal barrier, a bottleneck in the development of oligonucleotide therapeutics.

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Section: Delivery Platforms To Enhance Oligonucleotide Therapeutics I...mentioning

confidence: 99%

Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking

Mangla,

Vicentini,

Biscans

2023

Cells

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“…oligonucleotides, 12-30 long nucleotides, designed to bind to RNA by Watson-Crick base pairing rules [7]. By using nucleotide hybridization as the primary means to achieve specificity, stability, and efficiency of the resulting duplex structure [8], ASOs can modulate gene expression through various mechanisms, including inhibition of translation, induction of mRNA degradation via RNase H-mediated cleavage, or alteration of mRNA splicing patterns (Figure 2). The field of antisense technology has undergone different phases of development, from initial enthusiasm to a period of disillusionment; the numerous clinical trials currently in progress provide grounds for renewed optimism.…”

Section: Introductionmentioning

confidence: 99%

“…Generally, ASOs are defined as chemically synthesized oligonucleotides, 12–30 long nucleotides, designed to bind to RNA by Watson–Crick base pairing rules [ 7 ]. By using nucleotide hybridization as the primary means to achieve specificity, stability, and efficiency of the resulting duplex structure [ 8 ], ASOs can modulate gene expression through various mechanisms, including inhibition of translation, induction of mRNA degradation via RNase H-mediated cleavage, or alteration of mRNA splicing patterns ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

Yao,

Kasargod,

Chiu

et al. 2024

Antioxidants

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Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson–Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions.

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Synthesis and biophysical properties of tetravalent PEG-conjugated antisense oligonucleotide

Cited by 2 publications

References 33 publications

Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking

Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

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