It is the purpose of the present proposal to develop a gene transfer vector capable of specific and selective transduction of disseminated neoplastic cells. The development of a vector with this capacity would allow the targeting of malignant cells in situ after systemic delivery. Capitalizing on the unique capacity of recombinant adenoviral vectors to accomplish high efficiency in vivo gene delivery, it is the hypothesis of the investigators that further modifications of this vector may be achieved to alter parent virus tropism such that selective transduction of malignant cells may be accomplished.
The specific aim of this proposal is thus to modify the tropism of recombinant adenoviral vectors employing genetic and immunologic methods to modify the adenoviral fiber protein. The capacity of the tropism-modified adenoviral vectors to accomplish targeted tumor cell-specific transduction in vivo in the context of animal models of disseminated neoplastic disease will be determined. The derivation of this 'targetable injectable' vector system would represent a potentially powerful technical advance allowing the implementation of a variety of strategies to accomplish gene therapy for cancer.
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