Customize Consent Preferences

We use cookies to help you navigate efficiently and perform certain functions. You will find detailed information about all cookies under each consent category below.

The cookies that are categorized as "Necessary" are stored on your browser as they are essential for enabling the basic functionalities of the site. ... 

Always Active

Necessary cookies are required to enable the basic features of this site, such as providing secure log-in or adjusting your consent preferences. These cookies do not store any personally identifiable data.

Functional cookies help perform certain functionalities like sharing the content of the website on social media platforms, collecting feedback, and other third-party features.

Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics such as the number of visitors, bounce rate, traffic source, etc.

Advertisement cookies are used to provide visitors with customized advertisements based on the pages you visited previously and to analyze the effectiveness of the ad campaigns.

Citation

  • Authors: Wang, T., Chen, Y., Ronald, J. A.
  • Year: 2019
  • Journal: Gene Ther 26 177-186
  • Applications: in vivo / tumour-activatable minicircles (TA-MCs) / in vivo-jetPEI

Method

Biomolecule: a gene-based cancer detection system called tumour-activatable minicircles (TA-MCs). We used it to detect melanoma lung metastases in mice with a sensitive and relatively affordable blood reporter assay. Mice were injected with TA-MCs when tumours reached ~150 mm3. TA-MCs (25 μg/mouse) were complexed with 2.4 μL of linear polyethylenimine to achieve an N/P ratio of 6. This DNA–jetPEI complex was then resuspended in 50 μL 10% (w/v) glucose. Mice were anesthetised with 2% isoflurane then IT injections were performed by injecting the MC-PEI complexes into 4 or 5 loci of each tumour.

Abstract

Early and accurate detection of cancer is essential to optimising patient outcomes. Of particular importance to prostate cancer is the ability to determine the aggressiveness of a primary tumour, which allows for effective management of patient care. In this work, we propose using gene vectors called tumour-activatable minicircles which deliver an exogenously encoded reporter gene into cancer cells, forcing them to produce a unique and sensitive biomarker. These minicircles express a blood reporter protein called secreted embryonic alkaline phosphatase mediated by the tumour-specific survivin promoter, which exhibits activity graded to prostate cancer aggressiveness. Together, these components underlie a detection system where levels of blood reporter are indicative of not only the presence, but also the metastatic potential of a tumour. Our goal was to assess the ability of tumour-activatable minicircles to detect and characterise primary prostate lesions. Our minicircles produced reporter levels related to survivin expression across a range of prostate cancer cell lines. When survivin-driven minicircles were administered intratumourally into mice, reporter levels in blood samples were significantly higher (p < 0.05) in mice carrying prostate tumours of high versus low-aggressiveness. Continued development of this gene-based system could provide clinicians with a powerful tool to evaluate prostate cancer aggressiveness using a sensitive and affordable blood assay.

Go to