Infectious Papillomavirus Pseudoviral Particles


This invention describes pseudoviral particles of papillomavirus capsids encapsidating DNA useful for gene therapy and as vaccines. The pseudoviral particles are made by co-expressing the papillomavirus L1, L2 and E2 genes in a cell line along with a vector comprising the useful DNA and DNA containing E2 protein binding sites (E2BS). It is the discovery of the inventors that the presence of the E2BS containing DNA results in the encapsidation of the DNA. The encapsidated DNA can be a gene to replace a defective gene, or can encode an antigen, for gene therapy or immunization respectively. Since papillomaviruses selectively multiply in epithelial cells, the capsids may be particularly useful for mucosal vaccines, and for delivering genes to epithelial tissues. The existence of many non-crossreacting serotypes of human papillomaviruses can be taken advantage of to eliminate the problem of immune rejection of a pseudoviral particle. The same gene or antigen encoding DNA can be incorporated in pseudoviral particles of different serotypes for multiple dosing. The inventors have demonstrated delivery of the neomycin resistance gene to mammalian cells with a BPV capsid encapsidating a vector consisting of the neomycin gene under control of a mammalian promoter and DNA containing E2 binding sites. Claimed are the pseudoviral particles, methods of making them, and methods of using them.

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Updated: Dec 1, 1998