Virosome-mediated gene therapy against hiv-1

Información del proyecto

Identificador del acuerdo de subvención: BMH4972503

Proyecto cerrado

Fecha de inicio 1 Octubre 1997

Fecha de finalización 31 Diciembre 2000

Financiado con arreglo a

• Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998

Coste total

Sin datos

Aportación de la UE

Sin datos

Coordinado por

Policlinico San Matteo (IRCCS)
Italy

Objetivo

- 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.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › ácido nucleico
• ciencias médicas y de la salud › biotecnología médica › ingeniería genética › terapia génica
• ciencias naturales › ciencias biológicas › bioquímica › biomoléculas › proteínas
• ciencias médicas y de la salud › ciencias de la salud › enfermedad infecciosa › virus de ARN › VIH
• ciencias médicas y de la salud › medicina clínica › oncología

Programa(s)

• FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998

Tema(s)

• 4.2.4 - Development of therapeutic agents

Convocatoria de propuestas

Datos no disponibles

Régimen de financiación

CSC - Cost-sharing contracts

Coordinador

Policlinico San Matteo (IRCCS)

• Aportación de la UE: Sin datos
• Dirección: Piazzale Golgi 2 ; 27100 Pavia ; Italia
• Coste total: Sin datos

Participantes (3)

Institut National de la Santé et de la Recherche Médicale (INSERM)

Francia

• Aportación de la UE: Sin datos
• Dirección: Parc Scientifique de Luminy ; 13288 Marseille
• Coste total: Sin datos

Katholieke Universiteit Leuven

Bélgica

• Aportación de la UE: Sin datos
• Dirección: 10,Minderbroedersstraat ; 3000 Leuven
• Coste total: Sin datos

UNIVERSITY OF GRONINGEN

Países Bajos

• Aportación de la UE: Sin datos
• Dirección: Antonie Deusinglaan 1 ; 9713 AV GRONINGEN
• Coste total: Sin datos