Development of Chimeric Adenoviruses for Malignant Glioma
2005 Seed Grant
Maciej Lesniak, M.D.
The University of Chicago
The success of gene therapy depends on efficient gene delivery into target cells. Viral vectors, in the forms of adenoviruses, have provided one potential means for the delivery of gene therapy. However, the potency of adenoviral agents is determined directly by their capability of infecting target cells. Most adenoviruses used for gene therapy have been based on serotype S (AdS). Unfortunately, expression of the primary receptor for AdS, or CAR, is deficient on malignant brain tumor cells. We therefore explored substituting the receptor binding domain of AdS with adenovirus serotype 3 (Ad3). Our preliminary data suggest that this chimeric virus exhibits superior potential for glioma gene therapy.
Since malignant gliomas remain one of the most devastating of human illness for which there is no cure, the development of novel therapeutic approaches is desperately needed. The creation chimeric viral vectors with enhanced potential not only for gene therapy but also oncolysis offers a powerful approach for combating these tumors and may offer a new direction in the design of gene therapy vectors for human disease.