Nano and Microtechnologies for the Delivery of Oligonucleotides with Gene Silencing Properties

Giuseppe De Rosa,Maria Immacolata La Rotonda

doi:10.3390/molecules14082801

Giuseppe De Rosa, Maria Immacolata La Rotonda

Open Access

https://doi.org/10.3390/molecules14082801

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Abstract

Oligonucleotides (ONs) are synthetic fragments of nucleic acid designed to modulate the expression of target proteins. DNA-based ONs (antisense, antigene, aptamer or decoy) and more recently a new class of RNA-based ONs, the small interfering RNAs (siRNAs), have gained great attention for the treatment of different disease states, such as viral infections, inflammation, diabetes, and cancer. However, the development of therapeutic strategies based on ONs is hampered by their low bioavailability, poor intracellular uptake and rapid degradation in biological fluids. The use of a non-viral carrier can be a powerful tool to overcome these drawbacks. Lipid or polymer-based nanotechnologies can improve biological stability and cellular uptake of ONs, with possibility of tissue and/or cellular targeting. The use of polymeric devices can also produce a prolonged release of the ON, thus reducing the need of frequent administrations. This review summarizes advantages and issues related to the main non-viral vectors used for ON delivery.

Highlights

In the last decades, the discovery of the intracellular pathways responsible for a number of disease states has led to the identification of new therapeutic targets
RNA interference (RNAi) relies on a multistep intracellular pathway in which a long double stranded RNA molecules is processed by the endoribonuclease, named Dicer, in small interfering RNAs [8]
The intravenous administration of small interfering RNAs (siRNAs) complexed with cationic liposomes in an animal model of subcutaneous tumor did not result in a higher intratumoral levels of the nucleic acid, compared with siRNA administered as naked

Summary

Introduction

The discovery of the intracellular pathways responsible for a number of disease states has led to the identification of new therapeutic targets. Sorensen et al showed a successful silencing of the marker gene (GFP) in liver after intravenous injection of cationic liposome/siRNA complexes in mice [41]. The intravenous administration of siRNA complexed with cationic liposomes in an animal model of subcutaneous tumor did not result in a higher intratumoral levels of the nucleic acid, compared with siRNA administered as naked.

Results

Conclusion