In vivo characterization of a prostate-specific antigen promoter-based suicide gene therapy for the treatment of benign prostatic hyperplasia

H. S. Park, J. Cheon, H. Y. Cho, Y. H. Ko, J. H. Bae, D. G. Moon, J. J. Kim

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    Abstract

    To develop a novel gene therapeutic modality for the effective treatment of benign prostatic hyperplasia (BPH), we investigated the properties of toxic gene therapy utilizing prostate-specific antigen (PSA) promoter driving herpes simplex virus thymidine kinase (HSV-TK) suicide gene to induce highly selective molecular ablation of epithelial cells with minimal systemic toxicity in canine prostate. Replication-defective recombinant adenoviral vectors containing HSV-TK gene under transcriptional control of long PSA promoter (Ad-PSA-HSV-TK) were developed and delivered in an situ manner. Briefly, laparotomies were performed and Ad-PSA-HSV-TK (1 × 109 PFUs) was injected into the left lateral lobe of prostate only on days 1 and 7 with appropriate prodrug acyclovir in adult Beagle dogs. The therapeutic efficacy was evaluated on the 56th experimental day. The striking apoptosis of epithelial cells was identified in the treated left half of canine prostate on TUNEL assay. On immunohistochemical studies, there was markedly decreased number of PSA-secreting epithelial cells compared to control. Also significant atrophy of prostate glands, associated with dense infiltration of lymphocytes and plasma cells, was identified in the treated side. The PSA promoter-based suicide gene therapy induced highly selective and definite ablation of epithelial cells in benign canine prostate. Our novel approach could open opportunity of gene therapeutic modality for the treatment of clinical BPH.

    Original languageEnglish
    Pages (from-to)1129-1134
    Number of pages6
    JournalGene Therapy
    Volume10
    Issue number13
    DOIs
    Publication statusPublished - 2003 Jul

    Keywords

    • Prostate-specific antigen
    • Prostatic hyperplasia

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics

    Fingerprint

    Dive into the research topics of 'In vivo characterization of a prostate-specific antigen promoter-based suicide gene therapy for the treatment of benign prostatic hyperplasia'. Together they form a unique fingerprint.

    Cite this