Ziel
- To construct highly potent, non-toxic anti-HIV genes and oligonucleotides with low immunogenicity and the capacity to inhibit most or all variants of HIV, as well as limit the onset of escape mutants.
- To improve transduction of HIV-infectable cells (T-lymphocytes, macrophages, and dendritic cells) through development and optimization of a gene delivery system based on reconstituted viral envelopes (virosomes).
In Western Europe an estimated 450,000 adults are living with HIV infection, and AIDS has become the leading cause of death among adults under age 45 in many Western European cities. Despite enormous efforts, traditional therapeutic approaches have failed to achieve long-term control of viral replication. The goal of our four-country research project is to advance the state of the art of gene therapy against HIV by developing safe, effective anti-HIV genes together with a highly efficient and specific gene delivery system.
The proposed research has two primary objectives:
1) to construct highly potent, non-toxicanti-HIV genes and oligonucleotides with low immunogenicity and the capacity to inhibit most, if not all, variants of HIV, as well as limit the onset of escape mutants;
2) to improve the efficiency of transduction of HIV-infectable cells(T-lymphocytes, macrophages, and dendritic cells) through development and optimisation of a gene delivery system based on reconstituted viral envelopes(virosomes). Because the viral membrane fusion protein is functionally incorporated in the virosomal membrane, virosomes are highly fusogenic and therefore provide a powerful system for delivery of encapsulated molecules into the cytosol of target cells.
The three-year, shared-cost RTD project is divided into five tasks;
1) The Italian group will develop HIV-1-specific antiviral genes and antisenseoligonucleotides that block HIV-1 gene expression by inhibiting the action of the HIV-l regulatory proteins Tat and Rev;
2) Chemical modifications of these genes and oligonucleotides will be performed by the Belgian group to increase antiviral efficacy (catalyticoligonucleotides) and ensure effective incorporation of the antiviral compounds into virosomes;
3) The Dutch group will assemble influenza-derived virosomes and incorporate the modified genes and oligonucleotides into the virosomes;
4) The French group will confer a cell-specific binding property on the virosomes, as well as attempt to lower the immunogenicity of virosomal delivery systems;
5) The Italian group will evaluate virosome-mediated delivery of antiviral nucleic acids into primary human T-lymphocytes, macrophages, and dendritic cells, as well as into micro-cultures of human tonsils. These methods can potentially replace the use of animal models.
When the virosome-mediated gene therapy system has been tested in human clinical trials and is approved for clinical use, it is expected to improve the prognosis for AIDS patients. This is pioneering work that is not being done at the national level in any European country because of the high cost and level of expertise needed. Thus this project will introduce a new medical technology, which can be applied to other disorders such as infectious diseases and cancer. The results of these collaborative studies will be made accessible in international conferences, and published in the open scientific literature.
Wissenschaftliches Gebiet (EuroSciVoc)
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
CORDIS klassifiziert Projekte mit EuroSciVoc, einer mehrsprachigen Taxonomie der Wissenschaftsbereiche, durch einen halbautomatischen Prozess, der auf Verfahren der Verarbeitung natürlicher Sprache beruht.
- NaturwissenschaftenBiowissenschaftenBiochemieBiomoleküleNukleinsäure
- Medizin- und GesundheitswissenschaftenMedizinische BiotechnologieGentechnologieGentherapie
- NaturwissenschaftenBiowissenschaftenBiochemieBiomoleküleProteine
- Medizin- und GesundheitswissenschaftenGesundheitswissenschaftenInfektionskrankheitRNS-VirusHIV
- Medizin- und GesundheitswissenschaftenKlinische MedizinOnkologie
Sie müssen sich anmelden oder registrieren, um diese Funktion zu nutzen
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Data not availableFinanzierungsplan
CSC - Cost-sharing contractsKoordinator
27100 Pavia
Italien