ADENOVIRAL-MEDIATED GENE-TRANSFER TO BLADDER IN-VIVO

This study was designed to examine the potential for gene therapy in b ladder in vivo using adenoviral vectors. Gene transfer to rat bladders was accomplished via direct intravesical instillation using a replica tion-defective adenoviral vector containing a marker gene encoding for Escherichia coli beta-galactosidase (beta-gal). Successful gene trans fer was confirmed by analyzing bladder samples for DNA and RNA using p olymerase chain reaction (PCR) with primers specific for beta-gal and adeno sequences, detecting beta-gal in full-thickness bladder wall usi ng specific histochemical staining (X-gal) and documenting recombinant protein production. Bladder architecture was preserved, without evide nce of distant spread of virus as assessed by PCR. Gene expression was evident for at least 7 days. In summary, bladder cells can be genetic ally altered using replication-deficient adenoviral vectors via simple intravesical instillation of vector. Introduction of exogenous geneti c material is a potentially powerful therapeutic modality for immunomo dulation of bladder neoplasms.