ADENOVIRUS DODECAHEDRON, A NEW VECTOR FOR HUMAN GENE-TRANSFER

Recombinant adenovirus is one of most efficient delivery vehicles for gene therapy. However, the initial enthusiasm for the use of recombina nt adenovirus for gene therapy has been tempered by strong immune resp onses that develop to the virus and virus-infected cells. Even though recombinant adenoviruses are replication-defective, they introduce int o the recipient cell, together with the gene of interest, viral genete s that might lead to fortuitous recombination if the recipient is infe cted by wild-type adenovirus, We propose the use of a dodecahedron mad e of adenovirus pentons or penton bases as an alternative vector for h uman gene therapy. The penton is a complex of two oligomeric proteins, a penton base and fiber, involved in the cell attachment, internaliza tion, and liberation of virus into the cytoplasm, The dodecahedron ret ains many of the advantages of adenovirus for gene transfer such as ef ficiency of entry, efficient release of DNA from endosomes, and wide r ange of cell and tissue targets. Because it consists of only one or tw o adenovirus proteins instead of the 11 contained in an adenovirus vir ion and it does not contain the viral genome, it is potentially a safe r alternative to recombinant adenovirus.