Gene Silencing
Genesis has established a new subsidiary company named Solirna Biosciences Ltd (soli: plural of solo) in recognition of the delivery of dual single strands of RNA to achieve gene inhibition throrugh the RNAi mechanism. Sollirna will be developing the novel single stranded gene silencing technology that was invented by Genesis scientists. A Japanese investment group will be providing funding to Solirna, with Genesis retaining a substantial ownership position.
Oncology
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 employing the new and powerful technology of RNA interference (RNAi) to develop new cancer therapeutics. Gene silencing by RNAi offers the advantages of inherent specificity and the ability to inhibit target genes considered undruggable with conventional small molecule drugs.
We are using RNAi to target the aberrant metabolism and nutrient transport characteristics of solid tumours that kill cancer cells by inhibiting their nutrient uptake and metabolic activity. We have identified siRNAs that lead to cancer cell death, and those that act synergistically with chemotherapeutic drugs in a combinatorial approach.
Immunology
From our functional genomics platform, a series of novel bioactive molecules have been investigated 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.
Its effects 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.
Its 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.
