SiRNA Induced Transcriptional Silencing Of HIV-1: Elucidating The Mechanisms And Exploring Options For Delivery
Funder
National Health and Medical Research Council
Funding Amount
$512,631.00
Summary
Current drug therapy for HIV is for life We have discovered a set of molecules that will turn off the ability of HIV to reproduce itself. These molecules are from a new family of RNA molecules . A single dose of these molecules suppress the ability of the virus to reproduce itself for more than a month. Further we have found ways of extending this supressive ability to greater than one year. These studies will tell us how these molecules work and how they might be effectively administered.
SiRNA Induced TGS Of Retroviruses: Elucidation Of Underlying Mechanisms And Their Application In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$371,502.00
Summary
AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechani ....AIMS To elucidate changes in DNA that accompany suppression of HIV growth caused by certain unusual RNA molecules that turn off the ability of HIV to reproduce and make the virus dormant within the infected cell. While we have discovered RNA molecules that can do this to HIV in the test tube, we wish to develop similar molecules that can be used in animal models, so that we can decide whether this technology can be developed for use in humans. We also wish to understand more clearlky the mechanisms underlying this effect. BACKGROUND These RNA molecules can suppress a range of pathogenic human viruses including HIV-1 in the test tube. Our novel approach appears to induce changes that are long lasting and are less susceptible to mutations by the virus that allow it to become resistant to other therapeutic strategies. RESEARCH PLAN Initially more work will be done in tissue culture to determine the optimal design of these molecules and the best way to administer them. The most promising of these designs will be tested in small groups of infected animals as a preliminary demonstration of efficacy. In parallel experiments will be performed to elucidate the mechanisms undelying the suppressive effects of these molecules. OUTCOMES AND SIGNIFICANCE This work will lead to a significant increase in our understanding of the way replication of HIV is regulated and will develop a promising new therapeutic strategy for this virus that may be applicable to other conditions.Read moreRead less
Macfarlane Adaptive Changes In HIV-1 Subtype C Envelope Glycoproteins Contributing To Pathogenicity.
Funder
National Health and Medical Research Council
Funding Amount
$310,787.00
Summary
HIV exists as multiple subtypes. The most commonly studied is type B (B-HIV). B-HIV is common in developed countries, but accounts for only a small fraction of HIV infections worldwide. Type C HIV (C-HIV) in Africa and Asia accounts for the majority of infections worldwide, yet very little is known about how C-HIV causes AIDS. We aim to understand how C-HIV causes AIDS. This is critical for development of drugs and vaccines specifically designed for those who are most urgently need.
Processes Underlying Establishment And Maintenance Of The Latent HIV Resevoir And Potential Impact Of Integrase Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$318,044.00
Summary
Therapy for HIV-infected individuals is currently able to control the growth of the virus, but cannot eradicate the viral infection. This is due to a pool of CD4+ T lymphocytes which contain HIV DNA in a latent state, ready to reactivate as soon as therapy is interrupted. This project aims to better understand how this pool of latently infected CD4+ T lymphocytes is established and maintained, particularly how it is linked to the essential T cell survival signal from interleukin 7.
Understanding The Side Effects Of HAART In HIV Patients
Funder
National Health and Medical Research Council
Funding Amount
$387,489.00
Summary
Combination therapy has dramatically improved the life expectancy of people living with HIV. However, the long term side effects of these medications can be significant. Not everyone treated with the same drugs suffers similar side effects. This project seeks to unravel factors that lead a given individual to experience particular side effects. Understanding why medication side effects occur will be critical in finding safer ways to treat HIV.
AIDS is caused by the human immunodeficiency virus type 1 (HIV-1). Long-term HIV infection leads to increased incidence of Kaposi's sarcoma, AIDS dementia complex, and immune dysfunctions. The HIV-1 Tat protein has been linked to disease progression. However, Tat is predominantly found in the cell nucleus while measurable levels in patient serum. This is not believed to be a passive event caused by dying cells. Here we will investigate how Tat is released by HIV-1 infected cells.
Whole Human Genone Expression Analysis In CD4+ CD8+ T Cells And Monocytes At Various Stages Of HIV Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
HIV is an important global problem and what happens to human gene machinery at the level of different cell types upon contact with HIV remains unclear. We have a novel approach of analysing whole human genome expression in relation to HIV in diverse blood cell types. Identification and understanding of key genes will provide insights into how restoration of the host immune system could be achieved in the future in combating HIV infection and possible cure.
In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extende ....In recent years it has become clear that certain white blood cells called CD8+ T lymphocytes or killer T cells are required to protect people against HIV. Unfortunately, current vaccines that produce or anti-HIV CD8 T cells only produce effective T cells for a short period. In this project we intend to test a novel vaccine vector called a Kunjin replicon, which promises to persistently produce or maintain effective T cells because the vaccine itself persists and continually immunises for extended periods. We intend to test the ability of this vaccine to persist and persistently produce effective CD8 T cells not only systemically in the blood system but also at mucosal surfaces, where HIV usually gains entry during sexual intercourse.Read moreRead less