The Uab Research Foundation

Victor N Krasnykh

David T Curiel

Igor Dmitriev

Joanne T Douglas

Ramon Alemany

The present invention provides means to modify the tropism of recombinant adenoviral vectors using genetic methods to alter the adenoviral fiber cell-binding protein. The present invention generates an adenovirus with modified fiber gene such that novel tropism is achieved. This recombinant adenovirus has a fiber gene modified in the HI loop domain.

Adenovirus vector containing a heterologous peptide epitope in the hi loop of the fiber knob

A modified adenovirus capable of overcoming the problem of low level of coxsackle-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to mutations in E1a or E1b genes.

Infectivity-enhanced conditionally-replicative adenovirus and uses thereof

The utility of adenovirus vectors (Ad) for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. The present invention presents a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a receptor-binding ligand.

Modified adenovirus containing a fiber replacement protein

The present invention provides a means for the propagation of adenovirus lacking the native tropism by using genetic methods to modify the fiber protein by addition of a C-terminal tag. The modified virus is then propagated in a cell line transfected with a sequence encoding an artificial receptor for the C-terminal tag on the modified fiber protein.

Fiber receptor-independent system for the propagation of adenoviral vectors

The present invention provides means to modify the tropism of recombinant adenoviral vectors using genetic methods to alter the adenoviral fiber cell-binding protein while maintaining the native trimeric protein biosynthesis profile. The present invention further provides means to specifically target particular cell types for infection with recombinant adenoviral vectors using genetic methods to alter the adenoviral fiber cell-binding protein.

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Birmingham, AL, United States of America

Victor N Krasnykh