RT Journal Article
SR Electronic
T1 Interaction with Blood Components Plays a Crucial Role in Asialoglycoprotein Receptor-Mediated in Vivo Gene Transfer by Galactosylated Lipoplex
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 484
OP 493
DO 10.1124/jpet.105.089516
VO 315
IS 2
A1 Shintaro Fumoto
A1 Shigeru Kawakami
A1 Kosuke Shigeta
A1 Yuriko Higuchi
A1 Fumiyoshi Yamashita
A1 Mitsuru Hashida
YR 2005
UL http://jpet.aspetjournals.org/content/315/2/484.abstract
AB In this study, we evaluated the effect of blood components (whole blood and serum) on asialoglycoprotein receptor-mediated in vivo gene transfer. The hepatic transfection activity of galactosylated lipoplex preincubated with serum was approximately 10 times higher than that without incubation after intraportal injection in mice. However, preincubation with whole blood significantly reduced hepatic transfection activity. Fluorescent resonance energy transfer analysis and agarose gel electrophoresis revealed that preincubation with serum reduced the degree of destabilization of the galactosylated lipoplex in blood, partially supporting enhanced hepatic transfection activity by preincubation with serum. Inhibition of hepatic transfection activity by predosing galactosylated bovine serum albumin indicated that the galactosylated lipoplex exposed to serum is recognized by asialoglycoprotein-receptors on hepatocytes. Inactivation of serum prior to mixing with galactosylated lipoplex reduced liver accumulation and completely abolished enhancement of hepatic transfection activity by preincubation with active serum, suggesting that not only the stability of the lipoplex in blood but also the serum opsonin activity plays important roles. Alternatively, preincubation with inactivated serum reduced the lung accumulation and inflammatory cytokine production of galactosylated lipoplex. The information provided by this study will be valuable for the future use, design, and development of galactosylated lipoplex for in vivo asialoglycoprotein receptor-mediated gene transfer. The American Society for Pharmacology and Experimental Therapeutics