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  • Review Article
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New short interfering RNA-based therapies for glomerulonephritis

Nature Reviews Nephrology volume 7, pages 407–415 (2011)Cite this article

Subjects

Abstract

Current treatments for glomerulonephritis are not satisfactory, and the development of new therapies would be indispensable. Short interfering RNAs (siRNAs) are promising candidates for molecular therapy because of their strong and specific gene-silencing effects. Despite rapid progress in research into the therapeutic uses of siRNAs, however, many hurdles must be overcome before siRNA-based therapies can be brought to the clinic. Most in vivo studies of siRNA-based therapy have been limited to local administration or delivery to specific target organs, including the liver. Therapies based on siRNAs for patients with glomerulonephritis show promise, although tissue-specific protocols using siRNAs have not yet been established for this indication. This Review aims to provide an overview of the current challenges in siRNA-based therapy, primarily with respect to glomerular targeting. In addition, novel delivery approaches for glomerulus-targeted, siRNA-based therapies are described.

Key Points

  • Short interfering RNAs (siRNAs) are promising therapeutic tools because of their strong gene-silencing effects and high selectivity

  • Appropriate delivery vehicles are needed for the application of siRNA-based therapy

  • Glomerulus-targeted therapy is not yet established because of the lack of a definitive delivery system

  • siRNA delivery vehicles based on block copolymers are superior to previously used vehicles, owing to their stability in the bloodstream, small size, safety, and efficient drug release

  • Block copolymers are suitable as vehicles for siRNA-based therapy in the treatment of glomerulonephritis

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Figure 1: Intracellular mechanisms of action of siRNAs and barriers to their therapeutic use in renal disease.
Figure 2: Self-assembling micelles used for siRNA delivery.
Figure 3: Characteristics of the filtration barrier that influence the delivery of siRNA-containing complexes to the kidney.

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Acknowledgements

The authors thank Y. Hori, S. Kaname, K. Kataoka, and N. Nishiyama for useful advice and criticism during the preparation of this paper.

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  1. Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hideki Shimizu & Toshiro Fujita

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H. Shimizu wrote the article and provided a substantial contribution to discussions of the content. T. Fujita provided substantial contributions to discussion of the content, as well as to reviewing and editing of the manuscript before submission.

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Correspondence to Toshiro Fujita.

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Shimizu, H., Fujita, T. New short interfering RNA-based therapies for glomerulonephritis. Nat Rev Nephrol 7, 407–415 (2011). https://doi.org/10.1038/nrneph.2011.61

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