Vectors for tissue-specific replication

Abstract

The invention generally relates to targeted gene therapy using recombinant vectors and particularly adenovirus vectors. The invention specifically relates to replication-conditional vectors and methods for using them. Such vectors are able to selectively replicate in a target tissue to provide a therapeutic benefit from the presence of the vector per se or from heterologous gene products expressed from the vector and distributed throughout the tissue. In such vectors, a gene essential for replication is placed under the control of a heterologous tissue-specific transcriptional regulatory sequence. Thus, replication is conditioned on the presence of a factor(s) that induces transcription or the absence of a factor(s) that inhibits transcription of the gene by means of the transcriptional regulatory sequence with this vector; therefore, a target tissue can be selectively treated.

1 - 8 . (canceled)  
     
     
         9 : A method for distributing a polynucleotide in a tissue in vivo, comprising introducing a replication-conditional vector containing said polynucleotide into said tissue, wherein said vector contains a gene essential for vector replication, the coding region of which gene is operably linked to a transcriptional regulatory sequence that functions specifically in said tissue so that replication of the vector occurs in said tissue and not in a tissue in which said transcriptional regulatory sequence does not function.  
     
     
         10 - 40 . (canceled)