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Delivery materials for siRNA therapeutics

Nature Materials volume 12, pages 967–977 (2013)Cite this article

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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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Authors and Affiliations

  1. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA

    Rosemary Kanasty & Daniel Anderson

  2. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA

    Rosemary Kanasty, Joseph Robert Dorkin, Arturo Vegas & Daniel Anderson

  3. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA

    Joseph Robert Dorkin

  4. Department of Anesthesiology, Children's Hospital Boston, Boston, 02115, Massachusetts, USA

    Arturo Vegas & Daniel Anderson

  5. Harvard-MIT Division of Health Sciences and Technology, Cambridge, 02139, Massachusetts, USA

    Daniel Anderson

  6. Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USA

    Daniel Anderson

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Correspondence to Daniel Anderson.

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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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