1. ¹Immunology and Virology Group, Mogam Biotechnology Research Institute, Yongin-si, South Korea
2. ²Emergency Medical Team and Nuclear Medicine Laboratory, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea
3. ³Protein Research Laboratory, Green Cross Corporation, Yongin-si, South Korea

Correspondence: Meehyein Kim, Immunology and Virology Group, Mogam Biotechnology Research Institute, 341, Bojeong-dong, Giheung-gu, Yongin-si, Kyonggi-do 449-913, South Korea. E-mail: mkim@mogam.re.kr

Received 10 October 2006; Accepted 11 March 2007; Published online 17 April 2007.

Abstract

Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (IV) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I–mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (2 mg/kg) in only a single treatment, and its persistent antiviral effect up to 8 days. The liver-targeted gene silencing was also shown by in vivo images, in which bioluminescent signals emitted from the liver were efficiently reduced after IV administration of luciferase-specific siRNA and DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a foundation for the development of a new class of promising therapeutics against hepatitis viruses or hepatocyte genes related to tumor growth.