Current antiretroviral therapy cannot cure HIV infection. This is based on the fact that, upon infection, HIV permanently integrates its genes (i.e. the proviral DNA) into the genome of the infected host cell. The aim of this project is to reverse infection by excision of the integrated proviral DNA from host cell genomes using the HIV-1-specific designer recombinase Brec1.  
  
Brec1 has been developed by collaboration of scientists of the Heinrich Pette Institute, Leibniz Institute for Experimental Virology (HPI) in Hamburg (Prof. Joachim Hauber) and the Technical University Dresden (Prof. Frank Buchholz). Brec1 expression in HIV-1-infected humanized mice demonstrated absence of cytopathic effects and lasting suppression of viremia to levels below the limit of detection. Brec1 may therefore represent an important component of novel curative HIV-1 therapies.    

A first-in-human phase Ib/IIa clinical Brec1 gene therapy trial, which received funding from the Federal Ministry of Education and Research (BMBF) and the Ministry of Science, Research and Equalities (BWFG) in Hamburg, was started early in 2019 at the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf (Prof. Nicolaus Kröger). During this trial, hematopoietic stem cells from HIV-infected patients will be genetically modified to express Brec1. In consequence, the respective progeny cells will, upon HIV-1 infection, excise the proviral DNA and will thereby remove, at least partially, HIV from the organism. In turn, viremia may be controlled and the patient’s immune system may be functionally reconstituted.

In the context of this first-in-human clinical gene therapy study, funding by ForTra gGmbH für Forschungstransfer of the Else Kröner-Fresenius-Stiftung (EKFS) enables the preparation of critical and essential administrative issues, particularly relating to study application, legal advice, intellectual property and technical implementation.

Here you can get further information.   

Project partners:
Prof. Dr. med. Nikolaus Kröger
Onkologisches Zentrum, Interdisziplinäre Klinik und Poliklinik für Stammzelltransplantation
Universitätsklinikum Hamburg-Eppendorf
Martinistraße 52, 20246 Hamburg

Dr. med. Olaf Degen
Ambulanzzentrum des Universitätsklinikum Hamburg-Eppendorf
Fachbereich Infektiologie
Martinistraße 52, 20246 Hamburg

Prof. Dr. rer. nat. Frank Buchholz
Medizinische Fakultät Carl Gustav Carus
TU Dresden
01307 Dresden