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siRNA - Small Interfering RNAs

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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.
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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...

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Related Experiment Video

Updated: Jul 11, 2025

MISSION esiRNA for RNAi Screening in Mammalian Cells

MISSION esiRNA for RNAi Screening in Mammalian Cells

Published on: May 12, 2010

Three 'E' challenges for siRNA drug development.

Shuai Guo¹, Mengjie Zhang¹, Yuanyu Huang²

¹School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing 100081, China; Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China.

Trends in Molecular Medicine

|November 11, 2023

Summary

This summary is machine-generated.

RNA interference (RNAi) therapeutics show promise for various diseases but face delivery challenges. Strategies like ligand conjugates and combination therapies aim to improve siRNA drug development and clinical translation.

Keywords:

drug development efficacy entry escape oligonucleotide siRNA therapeutics

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Last Updated: Jul 11, 2025

MISSION esiRNA for RNAi Screening in Mammalian Cells

MISSION esiRNA for RNAi Screening in Mammalian Cells

Published on: May 12, 2010

Porous Silicon Microparticles for Delivery of siRNA Therapeutics

Porous Silicon Microparticles for Delivery of siRNA Therapeutics

Published on: January 15, 2015

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery

Published on: May 2, 2019

Area of Science:

Biotechnology
Pharmacology
Molecular Biology

Background:

Small interfering RNA (siRNA) therapeutics are gaining traction, with six approved drugs and broad investigation for metabolic, cardiovascular, infectious, rare genetic diseases, cancer, and CNS disorders.
Despite progress, significant druggability challenges hinder the widespread clinical application of siRNA-based therapies.

Purpose of the Study:

To discuss the key challenges in siRNA therapeutics, focusing on the 'three E's: entry, escape, and efficacy.
To explore promising strategies for overcoming these hurdles and advancing siRNA drug development towards clinical translation.

Main Methods:

Review and synthesis of current literature on siRNA delivery and therapeutic challenges.
Analysis of emerging strategies including ligand-siRNA conjugates, novel modification geometries, and combination therapies.

Main Results:

Identified targeted accumulation/cellular uptake ('entry'), endolysosomal escape ('escape'), and in vivo performance ('efficacy') as critical barriers.
Highlighted diverse ligand-siRNA conjugates, expanded disease targets, novel modification geometries, and combination therapies as promising solutions.

Conclusions:

Addressing the 'three E' challenges is crucial for successful siRNA therapeutic development.
The proposed strategies offer potential pathways to enhance the clinical translation and broaden the application of siRNA drugs.