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Delivery materials for siRNA therapeutics

Abstract

RNA interference (RNAi) has broad potential as a therapeutic to reversibly silence any gene. To achieve the clinical potential of RNAi, delivery materials are required to transport short interfering RNA (siRNA) to the site of action in the cells of target tissues. This Review provides an introduction to the biological challenges that siRNA delivery materials aim to overcome, as well as a discussion of the way that the most effective and clinically advanced classes of siRNA delivery systems, including lipid nanoparticles and siRNA conjugates, are designed to surmount these challenges. The systems that we discuss are diverse in their approaches to the delivery problem, and provide valuable insight to guide the design of future siRNA delivery materials.

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Figure 1: RNA interference.
Figure 2: Common RNA-backbone modifications.
Figure 3: Cyclodextrin polymer nanoparticles.
Figure 4: Lipid structures and shapes.
Figure 5: DPC conjugates.
Figure 6: GalNAc–siRNA conjugates.
Figure 7: Self-assembly of oligonucleotide nanoparticles.

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Acknowledgements

The authors acknowledge the service to the MIT community of the late Sean Collier.

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D.A. has a research grant with Alnylam Pharmaceuticals.

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Kanasty, R., Dorkin, J., Vegas, A. et al. Delivery materials for siRNA therapeutics. Nature Mater 12, 967–977 (2013). https://doi.org/10.1038/nmat3765

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