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
Overcoming The Delivery Hurdle For Peptide Therapeutics: New Treatment For Autoimmune Diseases
Funder
National Health and Medical Research Council
Funding Amount
$574,955.00
Summary
Peptide blockers of a key potassium channel in T cells have been shown to be effective treatments for autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Our goal is to develop formulations of these peptides that will allow oral administration and thereby enhance their effectiveness as therapeutics.
Lipoceramic Technologies: A Solution To Low And Variable Bioavailability Of Poorly Soluble Anti-inflammatory Drugs
Funder
National Health and Medical Research Council
Funding Amount
$200,600.00
Summary
A novel oral drug delivery platform will be developed that improves the absorption of poorly soluble drugs from the GI tract, leads to improved clinical outcomes and has significant commercial value. This development will be based on the combination of formulation, in vitro analysis and in vivo animal model studies. An advanced prototype formulation will be established for celecoxib (a non-steroidal anti-inflamatory drug) that will be suitable for human phase 1 clinical trials.
Xenotransplantation Of Encapsulated Insulin-producing Pig Cells
Funder
National Health and Medical Research Council
Funding Amount
$763,316.00
Summary
The ideal treatment for insulin-dependent diabetes is the replacement of insulin-producing cells. Currently, this is carried out using a whole pancreas or experimentally with cells isolated from the pancreas of donor humans. Despite the success of these procedures, demand for human organs far exceeds supply, thus driving the search for suitable alternatives. Pigs are physiologically similar to humans, and insulin-producing cells can be easily isolated from the fetal pig pancreas as islet-like ce ....The ideal treatment for insulin-dependent diabetes is the replacement of insulin-producing cells. Currently, this is carried out using a whole pancreas or experimentally with cells isolated from the pancreas of donor humans. Despite the success of these procedures, demand for human organs far exceeds supply, thus driving the search for suitable alternatives. Pigs are physiologically similar to humans, and insulin-producing cells can be easily isolated from the fetal pig pancreas as islet-like cell clusters; 8% of the cells in the cluster produce insulin and the remaining cells develop this capability after transplantation. Transplantation requires chronic immunosuppression with drugs which increase the risk of infection and cancer. To many people with diabetes, the side effects will be greater than the potential benefit. Placing cells inside microcapsules made of a biologically inert material may prevent graft rejection without chronic immunosuppression. The Investigators have demonstrated that encapsulated insulin-producing pig cells survive and function when transplanted into diabetic immunodeficient mice, but not when xenografted into immunocompetent mice. It is hypothesised that this is due to an immunological or inflammatory response by the host in response to the shedding of molecules by the encapsulated pig cells. A pre-clinical model to test the efficacy of encapsulated insulin-producing pig cells is the humanized mouse. It is hypothesized that transient administration of anti-rejection drugs will be needed to allow the survival of pig cells xenografted into these mice and normalization of BGL once diabetes has been induced. The aims of this study are: 1. To assess the nature of the host response when encapsulated insulin-producing fetal pig cells are transplanted into diabetic BALB-c mice. 2. To normalize blood glucose levels (BGL) in diabetic humanized mice transplanted with encapsulated insulin-producing fetal pig cells.Read moreRead less