1. ¹Department of Molecular Physiology and Biophysics and Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
2. ²The Iowa City VA Medical Center, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA
3. ³Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA
4. ⁴David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Correspondence: Michael D. Henry, Department of Molecular Physiology and Biophysics and Pathology, Roy J. and Lucille A. Carver College of Medicine, 6-510 Bowen Science Building, University of Iowa, Iowa City, Iowa 52240, USA. E-mail: michael-henry@uiowa.edu

Received 17 July 2008; Accepted 6 August 2008; Published online 9 September 2008.

Abstract

A significant barrier to the successful general development of small-interfering RNA (siRNA) therapeutics is the ability to deliver them systemically to target organs and cell types. In this study, we have developed a mouse strain that will facilitate the evaluation of the efficacy of siRNA delivery strategies. This strain contains robust ubiquitous expression of firefly luciferase from germ line Cre-mediated recombination of the ROSA26-LSL-Luc allele. We show that luciferase is highly and uniformly expressed in all tissues examined. Using this mouse model, we describe a facile assay that enables the assessment of the pharmacodynamics of a systemically delivered siRNA formulation. These mice can also be used as universal donors, enabling the efficient and sensitive monitoring of cell trafficking or tissue transplantation. The primary advantage of this approach is that siRNA efficacy against a nonessential target can be easily evaluated in any tissue. This strain should generally enhance the ability to rapidly screen, compare and optimize various siRNA formulations for tissue-targeted or -enhanced systemic delivery in a preclinical development setting.