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Nat Rev Genet. 2015 Sep;16(9):543-52. doi: 10.1038/nrg3978.

Knocking down disease: a progress report on siRNA therapeutics.

Author information

1
1] Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. [2] Department of Clinical Sciences, Section for Oncology and Pathology, Lund University, 221 85 Lund, Sweden.
2
Program in Cellular and Molecular Medicine, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

Small interfering RNAs (siRNAs), which downregulate gene expression guided by sequence complementarity, can be used therapeutically to block the synthesis of disease-causing proteins. The main obstacle to siRNA drugs - their delivery into the target cell cytosol - has been overcome to allow suppression of liver gene expression. Here, we review the results of recent clinical trials of siRNA therapeutics, which show efficient and durable gene knockdown in the liver, with signs of promising clinical outcomes and little toxicity. We also discuss the barriers to more widespread applications that target tissues besides the liver and the most promising avenues to overcome them.

PMID:
26281785
PMCID:
PMC4756474
DOI:
10.1038/nrg3978
[Indexed for MEDLINE]
Free PMC Article

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