Adenoviral-mediated gene transfer to bladder in vivo.
This study was designed to examine the potential for gene therapy in bladder in vivo using adenoviral vectors. Gene transfer to rat bladders was accomplished via direct intravesical instillation using a replication-defective adenoviral vector containing a marker gene encoding for Escherichia coli beta-galactosidase (beta-gal). Successful gene transfer was confirmed by analyzing bladder samples for DNA and RNA using polymerase chain reaction (PCR) with primers specific for beta-gal and adeno sequences, detecting beta-gal in full-thickness bladder wall using specific histochemical staining (X-gal) and documenting recombinant protein production. Bladder architecture was preserved, without evidence of distant spread of virus as assessed by PCR. Gene expression was evident for at least 7 days. In summary, bladder cells can be genetically altered using replication-deficient adenoviral vectors via simple intravesical instillation of vector. Introduction of exogenous genetic material is a potentially powerful therapeutic modality for immunomodulation of bladder neoplasms.
Department of Surgery, University of California at Los Angeles 90024-6904.
B D
BD
Morris
K E
KE
Drazan
M E
ME
Csete
P E
PE
Werthman
M P
MP
Van Bree
J T
JT
Rosenthal
A
A
Shaked
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004279:DNA, Viral / Q000032:analysis; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D001743:Urinary Bladder / Q000166:cytology; D001616:beta-Galactosidase / Q000235:genetics
D004279:DNA, Viral; D012367:RNA, Viral; D001616:beta-Galactosidase