Preparation of Lipid-Conjugated siRNA Oligonucleotides for Enhanced Gene Inhibition in Mammalian Cells
Nucleic acid conjugates are promising drugs for treating gene-related diseases. Conjugating specific units like lipids, cell-penetrating peptides, polymers, antibodies, and aptamers either at the 3′- or 5′-termini of a siRNA duplex molecule has resulted in a plethora of siRNA bioconjugates with impr...
| Autores: | , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/250102 |
| Acesso em linha: | http://hdl.handle.net/10261/250102 |
| Access Level: | acceso abierto |
| Palavra-chave: | Lipids Ultrasounds Phosphoramidite chemistry Serum RNA interference siRNA conjugates siRNA delivery |
| Resumo: | Nucleic acid conjugates are promising drugs for treating gene-related diseases. Conjugating specific units like lipids, cell-penetrating peptides, polymers, antibodies, and aptamers either at the 3′- or 5′-termini of a siRNA duplex molecule has resulted in a plethora of siRNA bioconjugates with improved stabilities in bloodstream and better pharmacokinetic values than unmodified siRNAs. In this sense, lipid-siRNA conjugates have attracted a remarkable interest for their potential value in facilitating cellular uptake. In this chapter, we describe a series of protocols involving the synthesis of siRNA oligonucleotides carrying either neutral or cationic lipids at the 3′- and 5′-termini. The resulting lipid-siRNA conjugates are aimed to be used as exogenous effectors for inhibiting gene expression by RNA interference. A protocol for the formulation of lipid siRNA using sonication in the presence of serum is described yielding interesting transfection properties for cell culture without the use of transfecting agents. |
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