Neutralizing antibody evasion ability of adenovirus vector induced by the bioconjugation of methoxypolyethylene glycol succinimidyl propionate (MPEG-SPA)

Biol Pharm Bull. 2004 Jun;27(6):936-8. doi: 10.1248/bpb.27.936.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology*
  • Animals
  • Antibodies, Viral / genetics
  • Antibodies, Viral / pharmacology*
  • Female
  • Genetic Vectors / immunology*
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / chemistry
  • Propionates / administration & dosage*
  • Propionates / chemistry
  • Succinimides / administration & dosage*
  • Succinimides / chemistry

Substances

  • Antibodies, Viral
  • Propionates
  • Succinimides
  • Polyethylene Glycols
  • monomethoxypolyethylene glycol