Out-licensing

Development of a Membrane Bound Reporter Gene System: For Gene Delivery and Imaging

Introduction/Background

Gene therapy has been described as the forth revolution in medicine. Currently, a great deal of research centres and bio-technology companies have expended great effort to develop gene vectors to deliver therapeutic genes to defined tissues in vivo; however, the safety and specificity of the vectors are being questioned.

Aims/Hypothesis

The availability of sensitive and specific reporter genes is critical for the continued development and practice of human gene therapy.

Research

To be clinically useful, a reporter gene should display low immunogenicity to allow repeated administration and prolonged expression. In addition, the reporter should be specific to allow unambiguous identification of the location and extent of gene expression. Several reporter genes have been developed including green fluorescent protein, luciferase, herpes simplex type 1 virus thymidine kinase, cytosine deaminase and b–galactosidase. Expression of these exogenous gene products, however, can induce immune responses that result in tissue damage and limit persistent gene expression and imaging. Endogenous reporter genes such as the dopamine D2 receptor and the transferrin receptor are not immunogenic but suffer from poor specificity due to their widespread expression.

To overcome these problems, we developed a membrane-anchored form of mouse b-glucuronidase (memzyme as a reporter gene to enzymatically convert a non-fluorescent glucuronide probe (fluorescein di-b-D-glucuronide, FDGlcU) to a highly fluorescent reporter to assess the location and persistence of gene expression. The power of the memzyme approach with bG is based on several factors including:

Conclusion

This invention relates to the development of a non-invasive reporter gene that can trace the gene expression in vivo. The bG memzyme imaging system appears to possess great potential for monitoring gene expression in animals and humans.

Relevance/Opportunity

This system has applications in the estimating the efficiency, safety and specificity of different gene delivery systems in vivo, accelerating Gene Delivery Systems approval by the FDA, imaging tissue specific promoter gene expression in transgenic animals, imaging of glucuronide prodrug cancer therapy and combined imaging and therapy with a single gene. Please enquire quoting reference no. 12A-950313 if you are interested in licensing partnerships.

Preclinical