ArticleNucleic acids research2019
Diverse lipid conjugates for functional extra-hepatic siRNA delivery in vivo.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Albumin-binding dendrimer-conjugated siRNA enables safe and effective gene silencing throughout the central nervous system.Nucleic acids research · 2026Article
- 1'-Sugar-Tethered Cholesterol-Modified siRNAs with Variable Linker Lengths for Carrier-Free Delivery and Enhanced RNAi Efficiency.ACS omega · 2026Article
- 5'-Palmitate Lipid and Internal LNA-Piperidyl Triesters Enhance the RNA Affinity and Activity of Splice-Switching Oligonucleotides.Journal of the American Chemical Society · 2026Article
- Investigating theBioconjugate chemistry · 2026Article
- Precision RNAi for Fibrodysplasia Ossificans Progressiva: a combinatorial, unimolecular, allele selective approach.Research square · 2026Article
- Sequence-Defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.bioRxiv : the preprint server for biology · 2026Article
- Therapeutic delivery of albumin-binding siRNA targeting IRS2 to diverse cell types reduces mammary tumor growth.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Programmable Lipid Functionalization of Nucleic Acid Nanoparticles Modulates Liver Cell-Type Targeting.ACS applied materials & interfaces · 2026Article
- [Anti-inflammatory effects of cell membrane vesicle-mediated delivery of small interfering RNA targeting tumor necrosis factor-α on dental pulp stem cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026Article
- An autonomous siRNA delivery system targeting NLRP3: implications in Parkinson's disease.BMC medicine · 2026Article
- Advancements in RNA-based therapies from bench to bedside.npj drug discovery · 2026Review
- Model selection in preclinical nucleic acid therapeutics research.Communications biology · 2026Review
- Intradermal delivery of lipophilic siRNAs enables prolonged skin retention and sustained gene silencing in a porcine model.Nature communications · 2026Article
- Review
- The efficacy of oligonucleotide-based gene therapeutics in gene silencing.Theranostics · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Functionalizing Nucleic Acids: Synthesis and Purification Strategies for Bioconjugates as Biomaterials.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2Journal of medicinal chemistry · 2025Article
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
Abstract
Small interfering RNA (siRNA)-based therapies are proving to be efficient for treating liver-associated disorders. However, extra-hepatic delivery remains challenging, limiting therapeutic siRNA utility. We synthesized a panel of fifteen lipid-conjugated siRNAs and systematically evaluated the impact of conjugate on siRNA tissue distribution and efficacy. Generally, conjugate hydrophobicity defines the degree of clearance and the liver-to-kidney distribution profile. In addition to primary clearance tissues, several conjugates achieve significant siRNA accumulation in muscle, lung, heart, adrenal glands and fat. Oligonucleotide distribution to extra-hepatic tissues with some conjugates was significantly higher than with cholesterol, a well studied conjugate, suggesting that altering conjugate structure can enhance extra-hepatic delivery. These conjugated siRNAs enable functional gene silencing in lung, muscle, fat, heart and adrenal gland. Required levels for productive silencing vary (5-200 μg/g) per tissue, suggesting that the chemical nature of conjugates impacts tissue-dependent cellular/intracellular trafficking mechanisms. The collection of conjugated siRNA described here enables functional gene modulation in vivo in several extra-hepatic tissues opening these tissues for gene expression modulation. A systemic evaluation of a panel of conjugated siRNA, as reported here, has not previously been investigated and shows that chemical engineering of lipid siRNAs is essential to advance the RNA therapeutic field.
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Registered trials
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