ArticleNucleic acids research2012
Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group.
Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 93 citations in OpenAlex.
- 1'-Sugar-Tethered Cholesterol-Modified siRNAs with Variable Linker Lengths for Carrier-Free Delivery and Enhanced RNAi Efficiency.ACS omega · 2026Article
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- 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
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Review
- piRNA28846 has the potential to be a novel RNA nucleic acid drug for ovarian cancer.NPJ precision oncology · 2025Article
- Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.Pharmaceutics · 2024Review
- Article
- Cholesterol Conjugates of Small Interfering RNA: Linkers and Patterns of Modification.Molecules (Basel, Switzerland) · 2024Article
- Fork- and Comb-like Lipophilic Structures: Different Chemical Approaches to the Synthesis of Oligonucleotides with Multiple Dodecyl Residues.International journal of molecular sciences · 2023Article
- Nucleic acid amphiphiles: Synthesis, properties, and applications.Molecular therapy. Nucleic acids · 2023Review
- Convenient Solid-Phase Attachment of Small-Molecule Ligands to Oligonucleotides via a Biodegradable Acid-Labile P-N-Bond.Molecules (Basel, Switzerland) · 2023Article
- Delivery of Oligonucleotides: Efficiency with Lipid Conjugation and Clinical Outcome.Pharmaceutics · 2022Review
- An Influence of Modification with Phosphoryl Guanidine Combined with a 2'-O-Methyl or 2'-Fluoro Group on the Small-Interfering-RNA Effect.International journal of molecular sciences · 2021Article
- Orthosteric and Allosteric Dual Targeting of the Nuclear Receptor RORγt with a Bitopic Ligand.ACS chemical biology · 2021Article
- Transport Oligonucleotides-A Novel System for Intracellular Delivery of Antisense Therapeutics.Molecules (Basel, Switzerland) · 2020Article
- Trimeric Small Interfering RNAs and Their Cholesterol-Containing Conjugates Exhibit Improved Accumulation in Tumors, but Dramatically Reduced Silencing Activity.Molecules (Basel, Switzerland) · 2020Article
- Review
- Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA.Frontiers in pharmacology · 2020Review
- Improving cellular uptake of therapeutic entities through interaction with components of cell membrane.Drug delivery · 2019Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.
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Registered trials
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