Important legal notice
Contact   |   Search on Europa   

Infectious Diseases Graphic element print icon Graphic element
  Homepage
Graphic element General information
  RTD Infectious Diseases Unit
  Developing countries
  EDCTP
   
Graphic element Projects
  About FP6 Funding
  FP6 projects
  About FP5 Funding
  FP5 projects
   
   
Graphic element Addressed Diseases
  HIV/AIDS
- News
  Malaria
  Tuberculosis
   
Graphic element Calls for proposals
  FP7 Calls
   
Graphic element Contact corner
  Unit
  Scientific officers
  Subscribe to our mailing list
   
 
HIVSTOP
HIV/AIDS
Framework programme: 6
Call: 3
Project number: LSHP-CT-2006-037301
EC contribution: € 2,250,000
Duration: 36 Months
Type: STREP
Starting date: December 2006
Graphic element Development of an Effective RNA Interference-Based Anti-HIV-1 Therapy Using an SV40-Derived Vector
Keywords: Therapeutic Molecular Vaccination, HIV-1, AIDS, SV40-Vector and RNA Interference.

Summary:

The Acquired Immunodeficiency Syndrome (AIDS) caused by infection with the human immunodeficiency virus type 1 (HIV-1) is a pandemic continuing to grow at an alarming rate, despite the availability of highly active anti-retroviral chemotherapy (HAART). The World Health Organisation (WHO) and European Union (EU) therefore launched a co-ordinated action program to combat poverty-related communicable diseases, including AIDS.

In this project a novel therapy for the treatment of individuals infected with HIV-1 is to be developed. This therapy involves the application of RNA interference (RNAi) to prevent productive infection of new cells with HIV-1 and therefore eventually cure infection. An SV40-based vector will be used to transfer the therapeutic anti-HIV-1 sequence to T-cells of HIV-1 infected individuals in order to result in long-lasting improvements of their condition.

SV40 vectors are intrinsically safe, transfecting both non-dividing and dividing cells. In order to use this therapy in developing countries it is essential to keep the costs and complexity low. A producer cell line will therefore be generated in order to produce viral vector particles at high titres and focus on a singleadministration, long-lasting therapeutic molecular vaccination. The safety and efficacy of the developed therapeutic vaccine will be tested in vitro and subsequently in vivo using mouse and simian challenge models.

Background:

HAART can be effective; however, resistant viral strains do emerge. Eventually, these resistant variants can cause AIDS in treatment-resistant patients. A novel therapy that involves the application of RNA interference (RNAi) to prevent productive infection of new cells with HIV-1 and thus eventually cure infection is the aim of this project. So far, RNAi-based inhibition of HIV-1 replication has been accomplished through the introduction of virus-specific, synthetic short double-stranded RNAs. These are short interfering RNAs or DNA constructs encoding short hairpin RNAs. However, their use as therapeutic antiviral against HIV-1 is limited because of the rapid emergence of virus escape variants.

In order to solve this durability problem, DNA constructs encoding virusspecific long hairpin RNAs (lhRNAs) were developed. It was demonstrated recently that expression of such lhRNAs in target cells provides durable, sequence-specific and broad-spectrum inhibition of HIV-1 replication.

Aim:

To develop a novel therapy for the treatment of individuals infected with HIV- 1. This therapy involves the application of RNA interference (RNAi) to prevent productive infection of new cells with HIV-1 and so eventually cure infection.

An SV40-based vector will be used, and the costs and complexity will be kept low. Therefore a producer cell line will be generated, to produce viral vector particles at high titres and focus on a single-administration, long-lasting therapeutic molecular vaccination.

Expected results:

  1. Proof of safety and efficacy of the developed therapeutic vaccine tested in vitro and subsequently in vivo using mouse and simian immunodeficiency virus (SIV)/Cynomolgus macaque models.
  2. A producer cell line to produce viral vector particles at high titres

Potential applications:

Therapeutic anti-HIV-1 Vaccine.

Coordinator:

1 - Gerrit-Jan van Holst
Viruvation B.V., Wassenaarseweg
72, PO box 1048, 2302 BA
Leiden,
The Netherlands
Tel. +31 71 572 1749
E-mail: gerritjan.vanholst@viruvation.com
Website: www.viruvation.com

Partners:

Principal
Scientific
Participants
Official Address Other Information
2Dr Ben Berkhout AMC,
Meibergdreef 9,
PO box 22660
1100 DD Amsterdam,
The Netherlands
Tel. +31 20 566 7400
E-mail: e.h.albers@amc.uva.nl
Website: www.amc.nl
3Puri Fortes FIMA Avda. Pio XII 55
31008 Pamplona,
Spain
Tel.+34 948 194700
E-mail: pfortes@unav.es
Website: www.cima.es
4Neil Almond NIBSC Blanche Lane, South Mimms
EN6 3QG,
Potters Bar,
Great Britain
Tel. +44 1707 641220
Email: nalmond@nibsc.ac.uk
Website: www.nibsc.ac.uk

 
 
top
Graphic element