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
Novel Silver Nanoparticle Coatings For The Prevention Of Infection Of Biomedical Implants And Devices
Funder
National Health and Medical Research Council
Funding Amount
$455,305.00
Summary
This project targets infections associated with implants and biomedical devices such as catheters, pacemaker leads, knee and hip implants, by the development and evaluation of coatings delivering antibacterial silver ions. The novel coating method is more uniform and reproducible and can be applied to a wide range of biomedical implants and devices. The novel coatings will be tested for antimicrobial effectiveness and safety using cell and tissue culture methods and animal clinical studies.
Development And Application Of A Pressure-sensing Electropalatograph For The Assessment And Treatment Of Speech Disorder
Funder
National Health and Medical Research Council
Funding Amount
$200,750.00
Summary
A multidisciplinary team of researchers aim to develop a unique, advanced, computer-based speech device that speech pathologists can use to assess and treat a variety of speech disorders. The device will record the location, timing and pressure of tongue contacts against the roof of the mouth (palate) during speech using innovative sensors embedded in an artificial plate placed over the roof of the mouth. State-of-the-art 3D graphics will be used to display tongue-to-palate contacts to both spee ....A multidisciplinary team of researchers aim to develop a unique, advanced, computer-based speech device that speech pathologists can use to assess and treat a variety of speech disorders. The device will record the location, timing and pressure of tongue contacts against the roof of the mouth (palate) during speech using innovative sensors embedded in an artificial plate placed over the roof of the mouth. State-of-the-art 3D graphics will be used to display tongue-to-palate contacts to both speech pathologist and patient.Read moreRead less
The Development Of A Cross-strain And Cross-subtype Pre Pandemic Influenza Vaccine Using Savine Technology
Funder
National Health and Medical Research Council
Funding Amount
$159,500.00
Summary
The flu vaccines in use today work by inducing antibodies to surface proteins. Flu causes disease every year but occasionally a new strain arises that is distincly differnet from previous strains and can cause wides spread disease and deaths worldwide. Our new approach is to increase the level of T cells that can recognise and kill flu infected cells from all flu strains.
Ocular Implant For The Treatment Of Bacterial Endophthalmitis
Funder
National Health and Medical Research Council
Funding Amount
$483,446.00
Summary
We seek to develop an ocular implant for the treatment of bacterial endophthalmitis. The implant will be a small device that can be administered directly to the affected ocular cavity to release an antibiotic in a controlled manner to clear any infection. The implant will erode and leave no residue. It will be produced from a novel drug-polymer conjugate technology that allows polymer devices that comprise >50% drug to be made.