ArticleNucleic acids research2024
Efficacy, biodistribution and safety comparison of chemically modified antisense oligonucleotides in the retina.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed.
- To scramble or not: Steric blocking 2'-MOE/PS control antisense oligonucleotides across cellular models.Molecular therapy. Nucleic acids · 2026Article
- Antisense oligonucleotide-mediated disruption of mRNA localisation inhibits angiogenesis.Angiogenesis · 2026Article
- A therapeutic antisense oligonucleotide encompassing 2'-NAR molecular medicine · 2026Article
- Design of bifunctional RNA-binding compounds that can modulate siRNA hydrophobicity for deep penetration and gene silencing in the retina.Molecular therapy. Nucleic acids · 2025Article
- Review
- Decoding retinitis pigmentosa: molecular targets and therapy with focus on pre-mRNA splicing.Cellular and molecular life sciences : CMLS · 2025Review
- Modulation of TTR gene expression in the eye using modified siRNAs.Nucleic acids research · 2025Article
- Gene therapy shines light on congenital stationary night blindness for future cures.Journal of translational medicine · 2025Review
- Review
- Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases.Journal of clinical medicine · 2024Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Antisense oligonucleotides (AONs) are a versatile tool for treating inherited retinal diseases. However, little is known about how different chemical modifications of AONs can affect their biodistribution, toxicity, and uptake in the retina. Here, we addressed this question by comparing splice-switching AONs with three different chemical modifications commonly used in a clinical setting (2'O-methyl-phosphorothioate (2-OMe/PS), 2'O-methoxyethyl-phosphoriate (2-MOE/PS), and phosphorodiamidite morpholino oligomers (PMO)). These AONs targeted genes exclusively expressed in certain types of retinal cells. Overall, studies in vitro and in vivo in C57BL/6J wild-type mouse retinas showed that 2-OMe/PS and 2-MOE/PS AONs have comparable efficacy and safety profiles. In contrast, octa-guanidine-dendrimer-conjugated in vivo PMO-oligonucleotides (ivPMO) caused toxicity. This was evidenced by externally visible ocular phenotypes in 88.5% of all ivPMO-treated animals, accompanied by severe alterations at the morphological level. However, delivery of unmodified PMO-AONs did not cause any toxicity, although it clearly reduced the efficacy. We conducted the first systematic comparison of different chemical modifications of AONs in the retina. Our results showed that the same AON sequence with different chemical modifications displayed different splicing modulation efficacies, suggesting the 2'MOE/PS modification as the most efficacious in these conditions. Thereby, our work provides important insights for future clinical applications.
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