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
Analysis And Manipulation Of The Genome-wide Integration Signatures Of Gamma-retroviral And Lentiviral Vectors In Human Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$612,154.00
Summary
Gene therapy has been successful in treating several diseases involving the bone marrow, but has been associated with the development of leukaemia in a number of patients. The cause has been tracked to the gene transfer technology used and associated damage to the genetic blueprint of treated cells. In this study we plan to use high-throughput genetic analysis to better understand the nature of this damage and to develop strategies to improve the safety of the gene repair process.
A Gene Therapy Approach To Acute Myeloid Leukaemia: Reversion Of The Disease Phenotype
Funder
National Health and Medical Research Council
Funding Amount
$744,911.00
Summary
Acute myeloid leukaemia is a cancer of white blood cells in which there is uncontrolled cell growth filling up the blood with cells that do not function properly. The cells also invade various tissues causing further damage. The patient becomes increasingly compromised due to the lack of appropriate normal cell types. The present standard therapy involves radiation or chemicals which are toxic to the leukaemic cells. However, these treatments are also toxic to normal cells so very high doses tha ....Acute myeloid leukaemia is a cancer of white blood cells in which there is uncontrolled cell growth filling up the blood with cells that do not function properly. The cells also invade various tissues causing further damage. The patient becomes increasingly compromised due to the lack of appropriate normal cell types. The present standard therapy involves radiation or chemicals which are toxic to the leukaemic cells. However, these treatments are also toxic to normal cells so very high doses that might be more effective to kill the leukaemic cells can not be given. At the doses which can be administered, the leukaemia often (in greater than 50% of patients) becomes resistant. The present project seeks to use a novel treatment strategy in which genes are used to modify the genetic abnormalities present in these leukaemic cells thereby stopping their growth. This growth suppression will be specific to the leukaemic cells as it targets their abnormal genetics leaving normal cells alone. The gene therapeutics have already been identified in part and the aims of this grant are: 1. To show that the gene therapeutic approach is justified to selectively stop the leukaemic cells from growing. 2. To confirm novel means to identify the inhibitory genes. 3. To determine the best inhibitory gene(s). 4. To show how these inhibitory genes can be delivered to the patients' cells and to model their effect in animal models. This project would represent a paradigm shift in the treatment of leukaemia and also has implications for the treatment of other cancer types.Read moreRead less