Receptor-mediated gene delivery by folate-PEG-baculovirus in vitro.
Gene delivery using baculovirus is a promising approach for efficient and safe gene therapy compared with animal viruses. However, obstacles of baculovirus-mediated gene delivery include inactivation of baculovirus in human serum and whole blood and the lack of specificity in targeted delivery. Therefore, chemical modification of the viral surface with poly(ethylene glycol) (PEG) and a targeting ligand, such as folate, is necessary for stable and targeted gene delivery via receptor-mediated endocytosis. In this study, folate-PEG (F-PEG) was attached on the baculovirus surface to obtain efficiency and specificity of gene delivery. Composition of F-PEG and degree of capsid modification with F-PEG was determined using (1)H nuclear magnetic resonance ((1)H NMR) and fluorescamine assay, respectively. Folate-PEG-Baculovirus (F-P-Bac) showed enhanced transduction efficiency compared to PEG-Baculovirus (P-Bac) in folate receptor (FR)-positive KB cells. Moreover, this enhanced transduction was not observed in FR-negative HepG2 cells. Presence of free folate in the medium blocked the transduction of F-P-Bac, whereas transduction efficiency of P-Bac in the presence or absence of free folate was not changed significantly. This study thus suggests that F-P-Bac can be used as a receptor-mediated gene delivery system.
Kim
You-Kyoung
YK
Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
Choi
Jae Young
JY
Yoo
Mi-Kyong
MK
Jiang
Hu-Lin
HL
Arote
Rohidas
R
Je
Yeon Ho
YH
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D016367:Baculoviridae / Q000235:genetics*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000493:pharmacokinetics*; D018390:Gene Targeting / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D004247:DNA; D005492:Folic Acid