Providing a cure for HIV/AIDS by excising integrated proviral HIV-1 DNA
To date, no effective vaccine is available against HIV nor is it possible to cure the disease. The only option is life-long medication with a mix of highly active anti-retrovirals (HAART) to keep the disease under control. Unfortunately, however, long-term HAART therapy is frequently accompanied by emerging new toxicities, resulting in secondary complications that include metabolic disorders, osteoporosis, cardiovascular disease and chronic kidney disease. In contrast, transgenic expression of an engineered HIV-1 long terminal repeat (LTR) site-specific recombinase (Tre) has been shown to excise integrated proviral DNA, providing a novel and promising approach to eradicate HIV-1.
A hallmark of the retroviral life cycle is stable integration of the proviral DNA into the host cell genome. Due to this mechanism, neither current anti-retroviral combination drug therapies nor prevention of de novo infection are able to reverse an established HIV infection.
In order to overcome this limitation, an HIV-1 LTR-specific recombinase (Tre-recombinase) has been developed, accurately excising the integrated HIV-1 provirus from infected host cells and thereby reversing the HIV infection without cellular toxicity. Pronounced anti-viral effects have been demonstrated in vivo, using HIV-infected humanized mice. The innovative Tre-recombinase excises CCR5- and CXCR4-tropic HIV-1 from infected host cells, thereby providing a technology to cure HIV/AIDS.
The technology is offered for co-development with Provirex, a biomedical start-up project associated with the Heinrich Pette Institute – Leibniz Institute for Experimental Virology.
Preclinical studies are under way, and Tre technology will be further developed in clinical studies for the treatment of HIV/AIDS as well as possibly other retroviral infections.
In 2007, patent applications on Tre-recombinase and its production have been filed in all relevant markets (cf. EP07100206; PCT/EP2008/000021; AU2008204586, CA2674275, CN101622356, US2010172881). Further patent applications were added in 2010/11 (EP10005499.8; PCT/EP2011/002646) that cover a tailored Tre-recombinase with broad specificity, recognizing most HIV strains.