Improving The Safety Characteristics Of Lentiviral Vectors.
Funder
National Health and Medical Research Council
Funding Amount
$296,250.00
Summary
Gene therapy holds great promise for the treatment of many types of disease including inherited disorders, cancer and cardiovascular disorders. However, the potential of gene therapy has in many cases been limited by the lack of suitable technologies for gene delivery. We have developed a novel gene delivery vehicle from human immunodeficiency virus type 1 (HIV-1). Although this vehicle has many of the characteristics desired of a gene therapy vector its derivation from a retrovirus, particularl ....Gene therapy holds great promise for the treatment of many types of disease including inherited disorders, cancer and cardiovascular disorders. However, the potential of gene therapy has in many cases been limited by the lack of suitable technologies for gene delivery. We have developed a novel gene delivery vehicle from human immunodeficiency virus type 1 (HIV-1). Although this vehicle has many of the characteristics desired of a gene therapy vector its derivation from a retrovirus, particularly one with such an unenviable reputation, raises obvious safety concerns. In order to properly address this issue it is necessary that the vector is carefully designed and properly tested. This project aims to continue our rational, systematic and stepwise approach to the development of our vector with the aim of producing a vector that can be used with a high degree of confidence in its safety, such that it is suitable for clinical usage. Given the highly desirable properties of these vectors, and the wide range of diseases where their use is being considered, the availability of such a vector will have great significance for the widespread practical application of gene therapy. Indeed, several of the projects we are developing with our vector will in all likelihood lead to lead to clinical trials and it is clear that the conduct of these trials will depend on the availability of a suitable vector.Read moreRead less
Kunjin Virus Replicon-based Vaccine Vectors: New Developments And Applications
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of ne ....The project is aimed towards further development of a unique gene expression and delivery system based on self-replicating RNA (replicon) of the nonvirulent Australian flavivirus Kunjin (KUN). A number of improvements in the design of KUN replicon vectors aimed to increase their efficiency and to optimize them for production of heterologous gene products with desired terminal sequences are proposed. Also proposed are improvements in the current KUN replicon packaging system and development of new packaging systems for production of large amounts of virus-like particles (VLPs) containing KUN replicon RNA enclosed in KUN coat proteins for use as potential vaccines. The vaccine potentials of the curent and newly developed KUN vectors and VLPs will be evaluated in mice using respiratory syncytial virus as a model. An entirely new direction proposed in this application is generation of chimeric fowlpox virus-KUN replicon vectors which will combine the advantages of both systems and may result in the generation of an ultimate vaccine vector.Read moreRead less
The Role Of Bone Morphogenetic Proteins In The Pathogenesis Of Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$236,540.00
Summary
Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened bo ....Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened both to find out new information about the disease process that affects the lung blood vessels and to offer a strategy for new treatments. The project will use a crippled form of the cold virus to deliver genes to the lining of the lung blood vessels, then see what impact that has on the pressure within the vessels and the ways in which they respond to certain stresses. These studies will be carried out using laboratory animals. If successful, it may be possible to eventually design such viruses to deliver genes which have a helpful therapeutic impact on the disease in patients.Read moreRead less