title: Multiple components in serum contribute to hepatic transgene expression by lipoplex in mice.
abstract: BACKGROUND
  Interaction of cationic liposome/plasmid DNA complex (lipoplex) with serum was not a limiting factor for in vivo transfection. After intraportal injection of lipoplex, hepatic transgene expression was enhanced by interaction with serum in mice. In the present study, we analyzed the mechanism of enhanced hepatic transgene expression of lipoplex by interaction with serum components.
  
  
  METHODS
  Lipoplexes were incubated with several serum components for 5  min at 37  ° C before administration. Transfection efficiency of lipoplexes was measured 6  h after intraportal injection of lipoplex in mice.
  
  
  RESULTS
  Depletion of divalent cation from serum decreased hepatic transgene expression. The addition of calcium ion to divalent cation-depleted serum restored transgene expression. Heat-inactivated serum and bovine serum albumin diminished the enhancing effect of serum on hepatic transgene expression. On the other hand, removal of anionic proteins from serum using an anion-exchanging column was critical for the enhancing effect of serum on transgene expression. Among the serum components tested, fibronectin and complement component C3 enhanced hepatic transgene expression.
  
  
  CONCLUSIONS
  Hepatic transgene expression by lipoplex was enhanced by interaction with multiple components in serum. Interaction of lipoplex with serum could be an important factor for successful in vivo gene transfer. Hence, the information obtained in the present study is valuable for the future development of effective gene carriers.
authors: Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors: Naoki
authors: N
authors: Yoshikawa
authors: Keiko
authors: K
authors: Sakamoto
authors: Sachiyo
authors: S
authors: Mizuno
authors: Junichiro
authors: J
authors: Sakaguchi
authors: Hirotaka
authors: H
authors: Miyamoto
authors: Toyoharu
authors: T
authors: Mine
authors: Hitoshi
authors: H
authors: Sasaki
authors: Shintaro
authors: S
authors: Fumoto
authors: Koyo
authors: K
authors: Nishida
mesh_terms: D000818:Animals; D017920:Antiporters / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002413:Cations, Divalent / Q000737:chemistry; D002852:Chromatography, Ion Exchange; D003176:Complement C3 / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004492:Edetic Acid / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008561:Membrane Fusion; D051379:Mice; D010957:Plasmids / Q000737:chemistry / Q000235:genetics*; D044967:Serum / Q000737:chemistry* / Q000187:drug effects; D014162:Transfection / Q000379:methods*; D019076:Transgenes
chemical_list: D017920:Antiporters; D002413:Cations, Divalent; D003176:Complement C3; D005353:Fibronectins; D008081:Liposomes; D004247:DNA; D004492:Edetic Acid; D002118:Calcium