Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 31, Pages 11479-11484Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604993103
Keywords
antibody; gene therapy; lentivirus; retrovirus; targeted gene delivery
Categories
Funding
- NIAID NIH HHS [R01 AI068978-01, R01 AI068978] Funding Source: Medline
Ask authors/readers for more resources
We have developed an efficient method to target lentivirus-mediated gene transduction to a desired cell type. It involves incorporation of antibody and fusogenic protein as two distinct molecules into the lentiviral surface. The fusogen is constructed by modifying viral envelope proteins, so that they lack the ability to bind to their cognate receptor but still retain the ability to trigger pH-dependent membrane fusion. Thus, the specificity of such a lentiviral vector is solely determined by the antibody, which is chosen to recognize a specific surface antigen of the desired cell type. This specific binding then induces endocytosis of the surface antigen, bringing the lentivirus into an endosome. There, the fusogen responds to the low pH environment and mediates membrane fusion, allowing the virus core to enter the cytosol. Using CD20 as a target antigen for human B cells, we have demonstrated that this targeting strategy is effective both in vitro and in intact animals. This methodology is flexible and can be extended to other forms of cell type-specific recognition to mediate targeting. The only requirement is that the antibody (or other binding protein) must be endocytosed after interaction with its cell surface-binding determinant.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available