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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...

Experimental RNAi

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...

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...

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...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

MicroRNAs

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...

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Related Experiment Video

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Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy

Published on: September 5, 2016

Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application.

Aimee L Jackson¹, Peter S Linsley

¹Regulus Therapeutics, Inc., 1896 Rutherford Road, Carlsbad, CA 92008, USA. ajackson@regulusrx.com

Nature Reviews. Drug Discovery

|January 1, 2010

Summary

Small interfering RNAs (siRNAs) offer powerful gene silencing for research and therapy. This review details off-target effects and mitigation strategies to improve siRNA specificity and safety.

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Area of Science:

Molecular Biology
RNA Interference
Biotechnology

Background:

Small interfering RNAs (siRNAs) are key tools for gene function studies and therapeutic development.
siRNAs have rapidly advanced into human clinical trials for diverse diseases.
The clinical application of siRNAs faces challenges, notably issues with specificity.

Purpose of the Study:

To outline the various types of off-target effects associated with siRNA technology.
To present methods for mitigating these off-target effects.
To facilitate the effective and safe application of siRNAs in research and medicine.

Main Methods:

Review of existing literature on siRNA off-target effects.
Categorization of different off-target mechanisms.
Discussion of strategies for reducing off-target activity.

Main Results:

siRNA off-target effects can arise from various mechanisms, complicating experimental interpretation.
These effects can lead to unintended toxicities in therapeutic contexts.
Several methods exist to minimize or avoid off-target activities.

Conclusions:

Addressing siRNA off-target effects is crucial for accurate gene function studies.
Mitigation strategies are essential for the safe and successful therapeutic use of siRNAs.
Further research and application of these strategies will enhance the utility of siRNA technology.