Hepatic siRNA delivery using recombinant human apolipoprotein A-I in mice.
Apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein (HDL), plays a key role in reverse cholesterol transport from peripheral tissues to liver or steroidogenic organs. Class B, type 1 scavenger receptor (SR-BI) is abundantly expressed in these target tissues and recognizes apo A-I of HDL for selective cholesteryl ester uptake. Recently, we reported the liver-targeting potential of plasma-derived apo A-I and the efficient delivery of therapeutic small interfering RNAs (siRNA) assembled with cationic liposome and apo A-I. In this study, we expressed and purified recombinant human apo A-I (rhapo A-I), low endotoxin grade, from an Escherichia coli expression system. The liver-targeting property of rhapo A-I was compared to that of plasma-derived apo A-I. Using a hepatitis C virus mouse model, intravenous administration of virus-specific siRNA with liposome and rhapo A-I significantly inhibited viral protein expression, demonstrating great promise for its use in clinical applications.
Lee
Hyeon
H
Virus Research Laboratory, Mogam Biotechnology Research Institute, 341 Bojeong-dong, Giheung-gu, Yongin-si, Gyeonggi-do 449-913, South Korea.
Kim
Soo In
SI
Shin
Duckhyang
D
Yoon
Yeup
Y
Choi
Tae Hyun
TH
Cheon
Gi-Jeong
GJ
Kim
Meehyein
M
D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000628:therapy*; D006801:Humans; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D014018:Tissue Distribution
D016632:Apolipoprotein A-I; D008081:Liposomes; D034741:RNA, Small Interfering; D011994:Recombinant Proteins