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RNAi Programme

 


Genesis has had an RNAi therapeutic development programme since 2003. Early work on silencing targets in allergic disease has lead to our current focus on oncology, with particular interest in the altered nutrient uptake and metabolism in cancer cells. The aim of the programme is to develop therapeutics that kill cancer cells in solid tumours and/or improve the effect of existing cytotoxic chemotherapeutic drugs.

We have identified a number of genes that have strong potential as therapeutic targets in cancer. Silencing these target genes inhibits tumour cell growth both in vitro and in vivo, and sensitises the cells to clinically used chemotherapeutic drugs. The screening programme has been expanded to provide a wider platform of potential targets that are suitable for internal development or external licensing.

Our development strategy includes parallel testing of various siRNA designs, lengths and chemistries together with the assessment of various delivery technologies from collaborators.

Targets

Gen-a12 

This receptor is overexpressed in prostate cancer with levels of expression increasing with severity of disease. Knockdown in prostate cancer cells inhibits growth.

 
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Gen-037

An enzyme involved in nucleotide metabolism, Gen-037 is upregulated in a number of solid tumours and expression is increased in gemcitabine resistant tumours and cell lines. RNAi-mediated knockdown of this target strongly inhibits growth and sensitizes tumour cells to gemcitabine treatment.

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Gen-071

The expression of this transcription factor is linked to aggressive forms of breast cancer, as well as other tumour types. Reducing the expression of Gen-071 strongly inhibits the growth of a number of tumour types in vivo.

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Novel Gene Silencing Technology

The application of RNAi in vivo, whether as a research tool or as a therapeutic agent, remains hampered by inefficient delivery of siRNAs. We are developing a next generation gene silencing technology which utilizes novel RNA modifications that can overcome the requirement for a delivery vehicle as well as increasing the activity of siRNAs and antisense oligos.

 

Oncology Consultants:

Dr Bruce Baguley BSc MSc(Hons) PhD FRSNZ
Professor Baguley is currently Professor and Co-Director of the Auckland Cancer Society Research Centre at the University of Auckland, where he has a particular interest in the development of tumour models, antivascular drugs and cytotoxic drugs. He is the author of over 360 scientific publications and has co-edited the book “Anticancer Drug Development”, which provided the first comprehensive overview of this field. He was selected a Fellow of the Royal Society of New Zealand in 1991. in 2002, he was made an officer of the New Zealand Order of Merit (ONZM) for services in cancer research and in 2006, he was awarded the Sir Charles Hercus Medal in molecular and cellular sciences and technologies.

Dr Mark McKeage MbChB MMedSc PhD
Dr McKeage is Associate Professor in Clinical Pharmacology at the University of Auckland. He has published widely on the clinical pharmacology and development of anticancer drugs, and has played an integral role in the successful development of two new cancer drugs. At Auckland City Hospital, Dr McKeage has an ongoing clinical role as a medical oncology specialist. He is an editorial board member of several international journals, a longstanding member of the SCOTT committee and the Cancer Society National Scientific Advisory Committee, and is current President of the New Zealand Society for Oncology.