Infectious Large Capacity Vectors For Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$374,625.00
Summary
The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Proje ....The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Project, genetics research will identify genes that are central to these processes, leading to gene-based medicine. Some of this new treatment will be drug-based but an alternative is the correction of the defective genes themselves gene therapy to either replace inherited faulty genes or to provide novel or modified genes that may help the repair and maintenance of tissue, or combat abnormal processes such as cancer. Gene therapy is a field still in its infancy with just a few qualified successes reported in the past few years. Persistent expression of a transgene at therapeutic levels is required for successful gene therapy. Most of the currently used vector and virus systems have a small capacity and usually employ a reduced (cDNA) copy of the transgene lacking natural control mechanisms. These are prone to vector loss and promiscuous expression or loss of expression. The delivery of genomic DNA up to 20 times this size would enable genes to be transferred in entirety, including their natural regulatory elements. This project aims to develop a vector system based on Herpesviruses that tackles some of the problems with the current generation of gene therapy vectors. This system is particularly aimed at providing long-term gene expresssion at physiological levels and safe, efficient delivery systems through the use of genomic DNA.Read moreRead less
Development Of Contemporary Surveillance And Control Methodologies For Dengue And Other Mosquito-borne Viral Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$512,290.00
Summary
This research proposal will address the need for better surveillance and control methodologies for mosquito-borne viral diseases and their vectors, including dengue and its global mosquito vector, Ae. aegypti, and a range of other important arboviral diseases throughout Australia. Research will focus in three areas: surveillance and control of Ross River and Barmah Forest viruses; development of contemporary risk management frameworks for dengue; and innovative investigations of insect age to pr ....This research proposal will address the need for better surveillance and control methodologies for mosquito-borne viral diseases and their vectors, including dengue and its global mosquito vector, Ae. aegypti, and a range of other important arboviral diseases throughout Australia. Research will focus in three areas: surveillance and control of Ross River and Barmah Forest viruses; development of contemporary risk management frameworks for dengue; and innovative investigations of insect age to provide evidence based monitoring and novel approaches to arbovirus disease prevention.Read moreRead less
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