ArticleNature biotechnology2022
Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 228 citations in OpenAlex.
- Barcoded oligonucleotide system (BOLT) for targeted organ delivery.Bioactive materials · 2027Article
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- Evaluating the effects of aging on distribution and gene silencing activity of lipid-siRNA conjugates delivered into cerebrospinal fluid.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1.Cell reports. Medicine · 2026Article
- 1'-Sugar-Tethered Cholesterol-Modified siRNAs with Variable Linker Lengths for Carrier-Free Delivery and Enhanced RNAi Efficiency.ACS omega · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Investigating theBioconjugate chemistry · 2026Article
- Evaluation and forecasting of siRNA delivery technologies: An analysis of hierarchical decision model based on patent data.Molecular therapy. Nucleic acids · 2026Article
- 5'-end uridine-derived base modification for siRNAs potency reinforcement.Cell & bioscience · 2026Article
- Brain-targeted delivery of siRNA via non-viral delivery systems, the therapeutic strategy for Alzheimer's disease-Unveiling challenges and prospects.International journal of pharmaceutics: X · 2026Review
- The RNA delivery dilemma-lipid versus polymer nanoparticle platforms.Drug delivery and translational research · 2026Article
- Immunogenicity Assessment for siRNA Therapeutics: A Risk-Based Proposal for Event-Driven Testing.The AAPS journal · 2026Review
- Evolution of siRNA Therapeutics: From Mechanistic Foundations to Clinical Expansion.Pharmaceutics · 2026Review
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity.RSC chemical biology · 2026Article
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- An acyclic nucleic acid-modified siRNA targeting CAG expansions for polyglutamine disease treatment.Molecular therapy. Nucleic acids · 2026Article
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- Combination therapy with tobevibart and elebsiran potently reduces hepatitis B virus surface antigen levels in preclinicalAntimicrobial agents and chemotherapy · 2026Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
54 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutics based on short interfering RNAs (siRNAs) delivered to hepatocytes have been approved, but new delivery solutions are needed to target additional organs. Here we show that conjugation of 2'-O-hexadecyl (C16) to siRNAs enables safe, potent and durable silencing in the central nervous system (CNS), eye and lung in rodents and non-human primates with broad cell type specificity. We show that intrathecally or intracerebroventricularly delivered C16-siRNAs were active across CNS regions and cell types, with sustained RNA interference (RNAi) activity for at least 3 months. Similarly, intravitreal administration to the eye or intranasal administration to the lung resulted in a potent and durable knockdown. The preclinical efficacy of an siRNA targeting the amyloid precursor protein was evaluated through intracerebroventricular dosing in a mouse model of Alzheimer's disease, resulting in amelioration of physiological and behavioral deficits. Altogether, C16 conjugation of siRNAs has the potential for safe therapeutic silencing of target genes outside the liver with infrequent dosing.
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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.