ArticleMolecular therapy. Nucleic acids2024
Single intravitreal administration of a tetravalent siRNA exhibits robust and efficient gene silencing in mouse and pig photoreceptors.
Article in Molecular therapy. Nucleic acids, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- An siRNA targetingMolecular therapy. Nucleic acids · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Prophylactic self-assembled nucleic acid hydrogel targeting retinal ganglion cell cuproptosis and microglial neuroinflammation for retinal ischemia-reperfusion injury.Bioactive materials · 2026Article
- Silencing Ubiquitin-Specific Peptidase 10 Alleviates Persistent Corneal Epithelial Defect in Mice.The American journal of pathology · 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
- Optimized chemical structure extends silencing duration of therapeutic siRNAs in dividing cancer and immune cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Multimeric Conjugates Using Engineered Peptide Scaffolds for Efficient siRNA Delivery.Bioconjugate chemistry · 2025Article
- A Therapeutic Small-Interfering RNA Potentiates Janus Kinase 1 Modulation for the Treatment of Dog Inflammatory Diseases.ACS pharmacology & translational science · 2025Article
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- Controversies and insights into PTBP1-related astrocyte-neuron transdifferentiation: neuronal regeneration strategies for Parkinson's and Alzheimer's disease.Translational neurodegeneration · 2024Review
- Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases.Journal of clinical medicine · 2024Review
- Optogenetics and Targeted Gene Therapy for Retinal Diseases: Unravelling the Fundamentals, Applications, and Future Perspectives.Journal of clinical medicine · 2024Review
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation.Nucleic acid therapeutics · 2024Review
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12 authors at 1 institution in 1 country.
Funding
Abstract
Inherited retinal dystrophies caused by dominant mutations in photoreceptor (PR) cell expressed genes are a major cause of irreversible vision loss. Oligonucleotide therapy has been of interest in diseases that conventional medicine cannot target. In the early days, small interfering RNAs (siRNAs) were explored in clinical trials for retinal disorders with limited success due to a lack of stability and efficient cellular delivery. Thus, an unmet need exists to identify siRNA chemistry that targets PR cell expressed genes. Here, we evaluated 12 different fully chemically modified siRNA configurations, where the valency and conjugate structure were systematically altered. The impact on retinal distribution following intravitreal delivery was examined. We found that the increase in valency (tetravalent siRNA) supports the best PR accumulation. A single intravitreal administration induces multimonths efficacy in rodent and porcine retinas while demonstrating a good safety profile. The data suggest that this configuration can treat retinal diseases caused by PR cell expressed genes with 1-2 intravitreal injections per year.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.