Bionomics and Louisiana State University collaborate on gene therapy

South Australian genomics company Bionomics (ASX:BNO) has shaken hands with Louisiana State University’s Health Sciences Centre (LSUHSC) on a landmark collaboration to explore the efficacy of the company’s gene-silencing constructs as a gene therapy for solid tumours.

A Bionomics research team led by Dr Gabriel Kremmidiotis has designed short interfering RNAs (siRNAs) to disrupt expression of the company’s proprietary gene target, BNO69.

The company’s researchers have shown that BNO69 is a key player in angiogenesis – the prolific growth of new blood vessels that fuels the growth of all solid tumours.

Bionomics has designed the prototype siRNA “magic bullets”, and Associate Prof J Michael Mathis has developed an adenoviral delivery system that will be genetically modified, to selectively target rapidly dividing vascular endothelial cells, and cause them to self-destruct.

Kremmiditiotis’ team has designed four siRNAs, all around 19 to 20 nucleotides in length – the optimal length needed to induce the native gene-silencing mechanism present in the cells of all eukaryotic life forms, including mammals.

Each construct targets a selected DNA sequences in the BNO69 gene, an early player in the cascade of genetic events that coordinates the supply of vascular endothelial cells to build new blood vessels.

Kremmidiotis says Bionomics researchers have tested each construct independently for its BNO69-silencing activity, and the best will be used in the adenoviral delivery system.

Mathis’ group at the LSUHSC Gene Therapy Centre has been experimenting with its adenoviral vector as a delivery system to transiently restore function of the vital P53 tumour-suppressor gene in cancerous cells. The silencing of P53 by mutation is one of the key events that tips pre-cancerous cells into cancerous growth.

Rather than restoring function to a disabled gene, Mathis’ team will test Bionomics BNO69 siRNA constructs for their ability to shut down the rampant growth of epithelial cells that form new blood vessels in established tumours.

The LSUHSC team tests its gene therapies in a mouse model of human cancer – an immunodeficient mouse that accepts cancerous human tissue grafts.

Tumours grow so rapidly that they live on the brink of oxygen debt – Kremmidiotis says a tumour deprived of its blood supply should be unable to grow to more than about 2mm in size.

More importantly, Kremmidiotis said, an effective BNO69-silencer will also prevent primary tumours metastasising – new blood vessels are the conduits by which cancerous cells escape the primary tumour to spawn potentially lethal secondary tumours in other organs.

Bionomics will have commercial rights over any new cancer treatments that emerge from the collaborative project.

Kremmidiotis said a number of different tumour types will be investigated since it is expected that only certain forms of breast cancers may provide a good model to explore the potential of BNO69 gene-silencing as a novel therapy for treating a wider range of solid tumours.

Dr Deborah Rathjen, CEO and Managing Director of Bionomics, said anti-angiogenesis therapies were in the forefront of the latest approaches to cancer treatment.

Earlier this year the US Food and Drug Administration approved an anti-angiogenesis therapeutic for the treatment of colorectal cancer.

Bionomics has strong expertise in the field, represented in its proprietary Angene platform, which it is using to identify new ways to approach the treatment of cancer and ultimately develop new therapeutics.

Mathis’ and Kremmidiotis’ teams will also collaborate on research into cellular and animal models of cancer to generate new data and other intellectual property based on other angiogenesis genes discovered by Bionomics.