Keywords: Therapeutic Molecular Vaccination, HIV-1, AIDS, SV40-Vector and RNA Interference
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.
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.
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.
Therapeutic anti-HIV-1 Vaccine.
|Official Address||Other Information|
|2||Dr Ben Berkhout||
PO box 22660
1100 DD Amsterdam,
|Tel. +31 20 566 7400 |
FIMA Avda. Pio XII 55 |
|Tel.+34 948 194700 |
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|Tel. +44 1707 641220 |