Design of SiRNA Therapeutics from the Molecular Scale

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2013 Aug 27

PMID 23976875

Citations 19

Authors

Phillip Angart

Daniel Vocelle

Christina Chan

S Patrick Walton

Affiliations

Soon will be listed here.

Abstract

While protein-based therapeutics is well-established in the market, development of nucleic acid therapeutics has lagged. Short interfering RNAs (siRNAs) represent an exciting new direction for the pharmaceutical industry. These small, chemically synthesized RNAs can knock down the expression of target genes through the use of a native eukaryotic pathway called RNA interference (RNAi). Though siRNAs are routinely used in research studies of eukaryotic biological processes, transitioning the technology to the clinic has proven challenging. Early efforts to design an siRNA therapeutic have demonstrated the difficulties in generating a highly-active siRNA with good specificity and a delivery vehicle that can protect the siRNA as it is transported to a specific tissue. In this review article, we discuss design considerations for siRNA therapeutics, identifying criteria for choosing therapeutic targets, producing highly-active siRNA sequences, and designing an optimized delivery vehicle. Taken together, these design considerations provide logical guidelines for generating novel siRNA therapeutics.

Citing Articles

RNAi-Induced Gene Silencing against Chikungunya and COVID-19: What Have We Learned So Far, and What Is the Way Forward?.

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PMID: 39339965 PMC: 11437507. DOI: 10.3390/v16091489.

Cationic Liposomes Carrying HPV16 E6-siRNA Inhibit the Proliferation, Migration, and Invasion of Cervical Cancer Cells.

Sanchez-Meza L, Bello-Rios C, Eloy J, Gomez-Gomez Y, Leyva-Vazquez M, Petrilli R Pharmaceutics. 2024; 16(7).

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The Impact of Chemical Modifications on the Interferon-Inducing and Antiproliferative Activity of Short Double-Stranded Immunostimulating RNA.

Bishani A, Meschaninova M, Zenkova M, Chernolovskaya E Molecules. 2024; 29(13).

PMID: 38999177 PMC: 11243415. DOI: 10.3390/molecules29133225.

Antitumor Activity of Anti-miR-21 Delivered through Lipid Nanoparticles.

Zhang Z, Huang Y, Li J, Su F, Chun-Tien Kuo J, Hu Y Adv Healthc Mater. 2022; 12(6):e2202412.

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Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells Cultured in 3D Spheroids.

Bialkowska K, Komorowski P, Gomez-Ramirez R, de la Mata F, Bryszewska M, Milowska K Cells. 2022; 11(10).

PMID: 35626734 PMC: 9140188. DOI: 10.3390/cells11101697.

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