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siRNA - Small Interfering RNAs

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...

RNA Interference

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...

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Related Experiment Video

Updated: Jul 7, 2026

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Protocol for the Solid-phase Synthesis of Oligomers of RNA Containing a 2'-O-thiophenylmethyl Modification and Characterization via Circular Dichroism

Published on: July 28, 2017

Solid-phase synthesis of siRNA oligonucleotides.

Serge L Beaucage¹

¹Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food & Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA. serge.beaucage@fda.hhs.gov

Current Opinion in Drug Discovery & Development

|February 20, 2008

Summary

Small interfering RNA (siRNA) therapeutics require efficient synthesis. Chemical modifications are crucial for developing stable and effective RNA interference (RNAi) gene-silencing agents for pharmaceutical applications.

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Area of Science:

Biochemistry
Molecular Biology
Medicinal Chemistry

Background:

RNA interference (RNAi) enables gene silencing via small interfering RNA (siRNA) oligonucleotides.
siRNAs are promising therapeutic agents targeting specific messenger RNAs (mRNAs).
This has increased demand for synthetic oligoribonucleotides and advanced RNA synthesis methods.

Purpose of the Study:

To develop rapid and efficient solid-phase RNA synthesis methods.
To identify essential biophysical and biochemical parameters for effective RNAi gene silencing.
To optimize chemical modifications for stable and potent siRNA therapeutics.

Main Methods:

Chemical modification of various siRNAs.
Evaluation of 2'-hydroxyl protecting groups for ribonucleoside phosphoramidites.
Assessment of coupling kinetics and efficiencies in solid-phase RNA synthesis.
Analysis of biophysical and biochemical properties of modified siRNAs.

Main Results:

Key 2'-hydroxyl protecting groups were identified for efficient RNA synthesis.
Optimized phosphoramidites demonstrated coupling comparable to deoxyribonucleoside phosphoramidites.
Chemically modified siRNAs showed enhanced stability and RNAi efficacy.
Essential parameters for effective and stable RNAi-mediated gene silencing were elucidated.

Conclusions:

Efficient chemical synthesis of RNA oligonucleotides is vital for pharmaceutical applications.
Strategic chemical modifications are necessary for developing potent and stable siRNA therapeutics.
This research advances the development of RNAi-based therapies.