Exploitation Of Unique Growth Factors To Develop New Products For Infertility Treatment
Funder
National Health and Medical Research Council
Funding Amount
$132,525.00
Summary
Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro ma ....Infertility comes at an enormous social and financial cost to Australian society; infertility is a major psychological burden on young couples and the technologies used to treat infertility, such as in vitro fertilisation (IVF), require expensive drugs to stimulate the ovary. The cost of these drugs to Medicare is expected to exceed $100 million p.a. over the next decade. A reproductive technology, which has always shown great potential to elevate some of this burden, is oocyte (egg) in vitro maturation (IVM), which drastically reduces the use-cost of drugs and the stress to patients. However, oocyte IVM has been slow to live up to its potential and the technology is still not in widespread clinical practice, mainly due to disappointing success rates in women. We have been studying oocyte IVM in animals for many years, and have recently made a significant technological breakthrough, improving success rates by ~50%. In this field, a 50% increase in efficiency is substantial and has significant clinical and commercial application. Currently, we are the only group worldwide with this technology. Over the course of this 2-year project we will conduct follow-up experiments to refine this discovery and investigate the feasibility of using this approach to treat human infertility. We are already in negotiations with two medical device manufacturers to licence this technology. We expect that this project will lead to a series of products and technologies that will enter a clinical trial for the treatment of infertility within 2-3 years.Read moreRead less
Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Kunjin Replicons For Gene Therapy And Protein Manufacture
Funder
National Health and Medical Research Council
Funding Amount
$310,000.00
Summary
This grant seeks to provide proof of concept (PoC) for the use of the Kunjin replicon technology for gene therapy and protein production. (A) Protein production. Two Kunjin replicon constructs expressing green fluorescent protein (GFP) and secreted alkaline phosphatase (SEAP) are to be constructed and protein production monitored using FACS and SEAP bioactivity reporter kit (Roche), respectively. Protein production and biological activity of the proteins will be monitored in transient transfecti ....This grant seeks to provide proof of concept (PoC) for the use of the Kunjin replicon technology for gene therapy and protein production. (A) Protein production. Two Kunjin replicon constructs expressing green fluorescent protein (GFP) and secreted alkaline phosphatase (SEAP) are to be constructed and protein production monitored using FACS and SEAP bioactivity reporter kit (Roche), respectively. Protein production and biological activity of the proteins will be monitored in transient transfections and over an extended time period. Several cell lines, culture conditions and Kunjin replicon vector modifications will be tested. Arrangements have also been made to send the constructs to Roche, GSK, Eli Lilly, and Exelixis for side by side comparisons of this system with existing proprietary protein production echnologies. (B) Gene therapy. Two PoC gene therapy systems are proposed to be used for evaluation of Kunjin replicon vectors. (i) Tumours expressing granulocyte macrophage colony stimulating factor (GMCSF) by transfection cause the generation of anti-tumour CD8 T cells and subsequent tumour rejection. Current approaches include adoptive transfer of adeno-GM-CSF transfected tumour cells, a costly and laborious process resulting in only transient expression (Can. Imm. Immunother 2001 50:373). We intend to inject Kunjin replicon virus like particles into growing s.c. B16 melanomas and expect to see a high infection rate, a sustained high-level expression of GMCSF, and rejection of the tumour. In contrast to Kunjin, nearly all humans have antibody responses to adenovirus, and very high titres of adenovirus are required to obtain high infection and GM-CSF expression. Both factors limit adenovirus use in vivo. (ii) Transplant rejection can be inhibited by expression in the graft of CTLA4-Fc a reagent that blocks T cell co-stimulation enhancing allo-graft acceptance (Transplantation 2000 69:1806). High-level expression for over 100 days is expected to correlate with optimal graft acceptance. Our ability to use Kunjin to express beta galactosidase for several months in vivo without inflammation illustrates the potential for this approach (CIB ref 15). Initially we intend to use P815 cells injected i.p. into C57BL-6, where they are usually rejected within a few days. In contrast, P815 cells with Kunjin replicon-mediated CTLA4-Fc expression should survive for an extended period. Graft survival is easily monitored using FACS and anti-H-2d antibodies.Read moreRead less
Synthesis And Purification Of Flavivirus-specific Antiviral Factor Mrasal
Funder
National Health and Medical Research Council
Funding Amount
$140,000.00
Summary
In this proposal we suggest to develop an anti-flaviviral compound based on naturally occurring host factors associated with inborn flavivirus resistance observed in mice. We propose to synthesise and purify a mouse protein factor encoded by a gene (Mrasal), which we have previously mapped by mouse genetics and positional cloning to a narrow 300 kb chromosomal region on mouse chromosome 5 carrying flavivirus resistance locus (Flv). When this mouse gene was isolated, sub cloned into a mammalian e ....In this proposal we suggest to develop an anti-flaviviral compound based on naturally occurring host factors associated with inborn flavivirus resistance observed in mice. We propose to synthesise and purify a mouse protein factor encoded by a gene (Mrasal), which we have previously mapped by mouse genetics and positional cloning to a narrow 300 kb chromosomal region on mouse chromosome 5 carrying flavivirus resistance locus (Flv). When this mouse gene was isolated, sub cloned into a mammalian expression vector pcDNA3tag and transiently transfected and expressed in cos-7 and Vero cells, its product conferred antiviral effect to a flavivirus Murray Valley encephalitis (MVE), but not to a non-flavivirus encephalomyocarditis virus (EMCV). Mrasal protein operates as an antiviral host factor and confers a flavivirus specific resistance at the cellular level. It could be directly used for the treatment-cure of acute flavivirus infections in vivo. Our aims are to produce and purify the Mrasal protein for the in vivo delivery as a therapeutic compound into susceptible mice during the acute phase of flavivirus infection: 1. To synthesise and purify Mrasal protein using baculovirus system. 2. To encapsulate the protein into liposomes ready to be used in mice. 3. To perform initial testing in a limited number of susceptible mice.Read moreRead less
Commercialisation Of A Glycoprofiling Diagnostic Kit And Novel Therapies For Biofilm Related Respiratory Disorders
Funder
National Health and Medical Research Council
Funding Amount
$203,050.00
Summary
Our preliminary studies have shown that a group of patients who suffer from chronic inflammatory disease and have bacterial biofilm identified on their mucosa have worse outcomes even after surgery. We have shown that they lack certain small protein and sugar molecules on their respiratory lining. We aim to use this technology as a diagnostic tool to aid the doctor in prescribing the appropriate treatment for these patients to prevent bacteria regrowing in their respiratory tract.
Development Of Novel Methods For Non-invasive Measurement Of Cardiac Output And Lung Volume During Anaesthesia
Funder
National Health and Medical Research Council
Funding Amount
$257,970.00
Summary
In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse ox ....In Australia approximately 2 million anaesthetic procedures are performed annually. Approximately one patient in 20,000 dies during or shortly after an anaesthetic from complications related to the anaesthetic itself, and as many as one in 170 suffers severe complications. Mortality and severe morbidity are often ultimately associated with lack of oxygen in the tissues. Oxygen is transported from the lungs to the tissues by the blood. The oxygen content of arterial blood is monitored by pulse oximetry during every anaesthetic, but blood flow is not. Cardiac output is measured in only a very small proportion of anaesthetised patients using intravenous catheters that pass through the heart to the lungs. This procedure is invasive and is associated with significant morbidity and mortality. At present there is no easy way to monitor cardiac output non-invasively during anaesthesia. Our proposed research project, currently underway in conjunction with an industrial partner, is aimed at the development of a reliable, rapidly repeating, non-invasive method for monitoring total cardiac output and lung volume in every patient who has an anaesthetic. The purpose of the new monitor is to ensure that potential problems with oxygen supply to the tissues are detected and corrected promptly. Our new monitoring technique is computer-controlled, can function without intervention by the anaesthetist and has very few side-effects. It can be added to any anaesthetic machine. Such a measurement technique is likely to have an impact on anaesthesia similar to that of pulse oximetry in the 1980's, and, if suitably adapted, is likely to find applications in other fields, such as intensive care, sports medicine, the respiratory function laboratory and in veterinary medicine.Read moreRead less
Development Of A PET Detection System Prototype With Depth Of Interaction Capability
Funder
National Health and Medical Research Council
Funding Amount
$360,906.00
Summary
This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and f ....This development project invovles the development of a slim-line Positron Emission Tomogrphy (PET) detection sub-module, the crucial component of PET scanners, that is small and extremely flexible. It is planned to utilize this module in the design of customized new commercial PET scanners ideal for diagnosing human brain and breast disorders. The development will proceed in collaboration with Insight Oceania-ADAC, Sydney. Insight Oceania-ADAC are very excited by the potential applications and future markets (Australia and overseas) of the newly developing PET detection sub-modules for dedicated PET scanners. Positron Emission Tomography (PET) is a functional imaging tool, which is able to quantify physiological and biochemical processes in vivo, using short-lived cyclotron-produced radiotracers. PET is emerging as an extremely important diagnostic procedure used in the early detection of cancers, neurological diseases and as an aid in treatment monitoring and drug development. The unique advantage of PET over anatomical imaging techniques, such as X-ray CT and MRI, arises from its ability to measure changes in tumour biology, at the molecular level, prior to anatomical changes in involved tissues, using trace amounts of a radiolabelled compound (radiotracer). The full potential of PET however, is not being completely utilized due to constraints within the current designs of PET scanners. When used to its full potential PET, in principle, would be an excellent diagnostic and treatment monitoring tool for breast cancer, brain tumours and other neurological conditions such as epilepsy, Alzheimer's, Parkinson's disease, post stress disorder, dementia, and depression. Lack of flexibility in current PET scanner designs to date has meant that no commercial human brain or breast imaging scanners exist. Pilot project data proved the feasibility of our new flexible PET detection module design.Read moreRead less