Neutralizing antibody evasion ability of adenovirus vector induced by the bioconjugation of methoxypolyethylene glycol succinimidyl propionate (MPEG-SPA).
Although adenovirus vectors (Ad) which possesses high transduction efficiency are widely used for gene therapy in animal models, clinical use is very limited. One of the main reason is that nearly 80% of human beings possess anti-Ad antibodies. In this study, we tried to modify Ad with methoxypolyethylene glycol (MPEG) activated by succinimidyl propionate, and, the neutralizing antibody evasion ability of PEGylated Ad was evaluated. The results demonstrated that PEG-Ad showed stronger protection ability against anti-Ad neutralizing antibody compared to that with unmodified-Ad. Considering there are many people carrying neutralizing antibody against Ad and readministration of Ad was necessary for treating chronic diseases, this strategy, which was also applicable to other vectors, can be used for developing improved vectors.
Eto
Yusuke
Y
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Gao
Jian-Qing
JQ
Sekiguchi
Fumiko
F
Kurachi
Shinnosuke
S
Katayama
Kazufumi
K
Mizuguchi
Hiroyuki
H
Hayakawa
Takao
T
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011422:Propionates / Q000008:administration & dosage* / Q000737:chemistry; D013388:Succinimides / Q000008:administration & dosage* / Q000737:chemistry
D000914:Antibodies, Viral; D011422:Propionates; D013388:Succinimides; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol