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Updated: May 19, 2026
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Preclinical biodistribution and safety study of reduced expression in immortalized
Morito Sugimoto1, Masami Watanabe, Haruki Kaku
1Department of Urology, Okayama University, Okayama 700-8558, Japan.
Abstract:
The biodistribution and safety of adenoviral vectors encoding the human REIC/Dkk-3 tumor suppressor gene (Ad-REIC) were examined in this preclinical study for in situ prostate cancer gene therapy. First, the in vitro apoptotic effects of Ad-REIC in normal and cancer cells derived from the prostate and liver were examined. Significant apoptotic effects were observed at 100 MOI (multiplicity of infection) in prostate cancer cells (LNCaP, PC3) and hepatoma cells (HEP3B and HEPG2); however, no effects were seen in normal cells. To analyze the safety of intraprostatic Ad-REIC administration, the biodistribution and histology after Ad-REIC injection were evaluated in various organs of normal male C57BL6 mice. In a supporting study, vector dissemination following intravenous injection of Ad-REIC into tail veins was determined. To evaluate whether Ad-REIC was present in the collected tissue specimens, human REIC gene detection was performed using DNA-PCR. Intraprostatic treatment administered at lower doses showed vector biodistribution into the colon, urinary bladder and prostate. At higher doses, vector dissemination was observed in tissues more distant from the prostate, including the lung, thymus, heart, liver and adrenal gland. After intravenous injection of Ad-REIC, dissemination was observed in the liver and spleen. These results indicate that the biodistribution of Ad-REIC is determined by the dose and route of administration. Although acute inflammatory effects were observed in the prostate after intraprostatic administration at higher doses, no abnormal histological findings were noted in the other tissues, including those of intravenously treated mice. Regarding the safety of Ad-REIC administration, no deaths and no signs of toxicity or unusual behavior were observed in the mice in any treatment group. Based on these preclinical experiments, adenovirus-mediated in situ REIC/Dkk-3 gene therapy is considered to be safe for use as a treatment for human prostate cancer.
Insights
Adenoviral vectors encoding the REIC/Dkk-3 tumor suppressor gene (Ad-REIC) show promising safety for prostate cancer gene therapy. Preclinical studies confirm Ad-REIC
Area of Science:
- Oncology
- Gene Therapy
- Viral Vector Technology
Background:
- Prostate cancer remains a significant health concern, necessitating novel therapeutic strategies.
- Adenoviral vectors offer a promising platform for delivering therapeutic genes.
- The REIC/Dkk-3 tumor suppressor gene has potential in cancer treatment.
Purpose of the Study:
- To evaluate the biodistribution and safety of adenoviral vectors encoding REIC/Dkk-3 (Ad-REIC).
- To assess the in vitro apoptotic effects of Ad-REIC on prostate and liver cells.
- To determine the safety profile of Ad-REIC for in situ prostate cancer gene therapy.
Main Methods:
- In vitro apoptosis assays using normal and cancer prostate/liver cells exposed to Ad-REIC.
- In vivo biodistribution and histological analysis in mice following intraprostatic and intravenous Ad-REIC administration.
- DNA-PCR used for detecting the human REIC gene in tissue specimens.
Main Results:
- Ad-REIC demonstrated significant apoptotic effects on prostate cancer and hepatoma cells, sparing normal cells.
- Biodistribution varied with dose and route; intraprostatic administration showed localized spread at low doses and wider dissemination at high doses.
- No deaths, toxicity, or significant abnormal histological findings were observed, indicating a favorable safety profile.
Conclusions:
- Adenovirus-mediated in situ REIC/Dkk-3 gene therapy (Ad-REIC) exhibits potent in vitro anti-cancer effects.
- Preclinical biodistribution and safety studies suggest Ad-REIC is well-tolerated with dose- and route-dependent spread.
- Ad-REIC represents a potentially safe and effective gene therapy strategy for human prostate cancer.
