Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways

Dirk Grimm, Konrad L. Streetz, Catherine L. Jopling, Theresa A. Storm, Kusum Pandey, Corrine R. Davis, Patricia Marion, Felix Salazar and Mark A. Kay ()
Additional contact information
Dirk Grimm: Stanford University, School of Medicine
Konrad L. Streetz: Stanford University, School of Medicine
Catherine L. Jopling: Department of Microbiology and Immunology
Theresa A. Storm: Stanford University, School of Medicine
Kusum Pandey: Stanford University, School of Medicine
Corrine R. Davis: Department of Comparative Medicine
Patricia Marion: Hepadnavirus Testing, Inc.
Felix Salazar: Hepadnavirus Testing, Inc.
Mark A. Kay: Stanford University, School of Medicine

Nature, 2006, vol. 441, issue 7092, 537-541

Abstract: Adverse reaction to shRNA It's early days, but RNA interference (RNAi) is already seen as a potentially important therapeutic technique for silencing genes. One way of delivering short interfering RNAs (siRNAs) in vivo involves cloning the siRNA sequence as a short hairpin into an adenovirus vector. When introduced into the animal, the hairpin sequence is expressed, forms a duplex RNA (shRNA), and is processed by the RNAi pathway. A study of the long-term effects of shRNA expression in the livers of adult mice strikes a note of caution, however. It turns out that many shRNAs are toxic when expressed in mice. The toxicity — often fatal — seems to result from competition between shRNAs and endogenous microRNAs for binding to exportin-5, a factor involved in transporting molecules out of the nucleus. There is growing interest in developing shRNA-based therapies, and until now there has been little evidence to suggest severe in vivo toxicity.

Date: 2006
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature04791 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:441:y:2006:i:7092:d:10.1038_nature04791

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature04791

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().