Prostate-specific targeting using PSA promoter-based lentiviral vectors.
The prostate-specific antigen (PSA) promoter is known to be highly tissue specific. Although its tissue specificity has been confirmed, its efficiency of gene transcription is significantly lower compared to known nonspecific viral promoters. These lower levels of promoter activity therefore pose a problem when developing an efficacious gene vector for prostate cancer gene therapy. Thus, selecting an appropriate therapeutic gene and vector system to carry the gene driven by the PSA promoter (PSAP) is important. In the studies described here, a human immunodeficiency virus (HIV)-1-based lentiviral vector carrying either the enhanced green fluorescent protein (EGFP) reporter or the diphtheria toxin A (DTA) gene was constructed. The results demonstrate that the PSA promoter in a lentiviral vector drives genes in prostate cells with satisfactory efficacy and specificity. The tissue-specific expression of the DTA protein efficiently eradicates LNCaP prostate cells in culture. We also infected prostate cancer cells and control cells carried by nude mice with the EGFP lentiviral vector. Significant numbers of EGFP-positive LNCaP cells were detected in all the mice bearing these tumors, but no EGFP-positive control cells were detected in any other mouse tissue. The high levels of expression in prostate cells, compared with the low levels of background expression in other cells, show that the PSAP-lentiviral vector could be a potential useful tool for gene therapy of metastatic prostate cancer.
Yu
D
D
Division of Oral Biology and Medicine, UCLA School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA.
Chen
D
D
Chiu
C
C
Razmazma
B
B
Chow
Y H
YH
Pang
S
S
D000818:Animals; D003094:Collagen; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000378:metabolism / Q000821:virology; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007279:Injections, Subcutaneous; D007797:Laminin; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011467:Prostate / Q000378:metabolism / Q000821:virology; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D011509:Proteoglycans; D014162:Transfection; D014407:Tumor Cells, Cultured
D004167:Diphtheria Toxin; D004338:Drug Combinations; D007797:Laminin; D008164:Luminescent Proteins; D010446:Peptide Fragments; D011509:Proteoglycans; C029795:diphtheria toxin fragment A; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen; D017430:Prostate-Specific Antigen