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Updated: Jun 8, 2026
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Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes
Published on: July 23, 2016
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Synthesis of Chemically Diverse siRNA-Lipid Conjugates Enabled by Reversible Adsorption to Solid Support (RASS).
Albert Kakkis1, Linzhongyi Sun1, Zhijie Xie1
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla California, 92037, USA.
Chembiochem : a European Journal of Chemical Biology
|June 5, 2025
Summary
Researchers developed a new method for modifying small interfering RNAs (siRNAs) using reversible adsorption onto a solid support. This technique allows for diverse lipid conjugations, expanding therapeutic possibilities for siRNA drugs.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Drug Delivery
Background:
- Small interfering RNAs (siRNAs) regulate gene expression and are promising therapeutic agents.
- Chemical modifications enhance siRNA stability, cellular uptake, and targeting.
- Postsynthetic lipidation is a key strategy, but current methods have limitations in chemical diversity.
Purpose of the Study:
- To develop a novel method for postsynthetic modification of siRNAs.
- To expand the chemical space of siRNA-lipid conjugates.
- To create siRNA therapeutics with improved pharmacokinetic properties.
Main Methods:
- Reversible adsorption of oligonucleotides onto a cationic solid support.
- Multistep, postsynthetic modification in neat organic solvent.
- Generation of siRNA-lipid conjugates with diverse lipid moieties.
Main Results:
- Demonstrated a novel method, RASS (Reversible Adsorption of Single-stranded/double-stranded siRNA), for siRNA modification.
- Successfully incorporated challenging lipid moieties, such as long-chain alkyl thioethers and polyfluorinated biphenyl groups.
- Obtained siRNA-lipid conjugates with significantly expanded chemical diversity.
Conclusions:
- RASS is a rapid and versatile approach for generating diverse siRNA-lipid conjugates.
- This method accelerates the discovery of potent siRNA therapeutics.
- Expanded chemical space of siRNA modifications holds promise for treating various diseases.
