Genesis seeks novel biologics which can be used as therapeutics or as targets for new drug therapies. Its primary disease targets are autoimmne diseases and cancers.
Immunology project:
From its functional genomics platform, Genesis investigated a series of novel bioactive molecules for their therapeutic potential. The most promising of these molecules is Zyrogen, the fifth member of the fibroblast growth factor receptor family (FGFR5). Zyrogen is a cell surface protein that is expressed by the stromal cells found in bone marrow and lymph nodes. These cells are rich in secreted and cell surface proteins that influence the development and mature functioning of the immune system. The expression of Zyrogen by stromal cells suggested that it might play a similar role.

The effects of Zyrogen on the immune system have been studied in a series of in vitro and in vivo experiments using a dimeric soluble form of the receptor generated by fusing the receptor’s extracellular domain to the Fc fragment of human IgG1.

Zyrogen’s ability to stimulate an autoimmune-like disorder in mice and to drive osteoclastogenesis in vitro suggest that antagonists will be of therapeutic benefit in autoimmune diseases, such as systemic lupus erythematosus (SLE), osteoporosis and cancer. Zyrogen antagonists may take the form of humanised monoclonal antibodies or small molecules.

It’s ability to promote an immune response to the Fc portion of the fusion protein when administered to mice indicates that Zyrogen is also an effective adjuvant. This finding, in conjunction with data indicating that it breaks immune tolerance to self (DNA), suggests that a fusion between Zyrogen and a cancer antigen may promote a therapeutic immune response.

Cancer project:
Cancer continues to be one of the leading causes of death world-wide, claiming more than seven million lives every year. Traditional treatments for cancer – surgery, chemotherapy and radiation therapy – all have significant limitations, and there remains an urgent need for new and innovative treatments. In our oncology program, we are utilising the new and powerful technology of RNA interference (RNAi) to develop new cancer therapeutics that kill cancer cells by inhibiting their nutrient uptake and metabolic activity.

Genesis is targeting changes in nutrient uptake and energy production, two important aspects of the different cellular physiology of tumour and normal cells. We aim to identify small interfering RNA (siRNAs) that lead to cancer cell death, and those that act synergistically with chemotherapeutic drugs in a combinatorial approach.