Providing a Cure for HIV/AIDS by Excising Integrated Pro-Viral DNA

Providing a cure for HIV/AIDS by excising integrated pro-viral DNA Reference Number TO 13-00037 Challenge To date, no effective vaccine against HIV is available 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, long-term HAART therapy is frequently accompanied by emerging new toxicities, Licensing Contact resulting in secondary complications that include metabolic disorders, osteoporosis, cardiovascular Dr Torsten Stachelhaus disease and chronic kidney disease. In contrast, transgenic expression of an engineered HIV-1 long Technology Manager T: +49 40 226 112-78 terminal repeat (LTR) site-specific recombinase (Tre) has been shown to excise integrated proviral DNA, F: +49 40 226 112-75 providing a novel and promising approach to eradicate HIV. [email protected] Ascenion GmbH Herzogstraße 64 D-80803 München T +49 (0) 89 31 88 14-0 F +49 (0) 89 31 88 14-20 [email protected] www.ascenion.de Berlin Braunschweig Hamburg Hanover Munich Neuherberg Eradication of HIV-1 from a human cells by Tre-recombinase. HIV-1 Gag expressing cells are visualized by green (Cy2) label. Technology 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 novel, powerful technology to cure HIV/AIDS. Commercial Opportunity The technology is offered for co-development with Provirex, a biomedical start-up project at the Heinrich Pette Institute – Leibniz Institute for Experimental Virology. Developmental Status Preclinical studies are under way, and Tre-recombinase technology will be further developed in clinical studies for the treatment of HIV/AIDS and other retroviral infections. Patent Situation In 2007, a first patent application on tailored Tre-recombinases for the treatment of HIV was filed and subsequently extended to cover all relevant markets (cf. EP07100206; PCT/EP2008/000021; AU2008204586, CA2674275, CN101622356, US2010172881). The corresponding patent has meanwhile been granted in most of those countries (incl. EP, US, CN, RU, AU, ZA), and is still pending in the few remaining. In 2010 and 2014, respectively, a second (EP10005499.8; PCT/EP2011/002646) and third patent application have beend added, covering and claiming tailored Tre-recombinases with broad specificity to recognize most HIV strains. Further Reading Sarkar et al. (2007) HIV-1 proviral DNA excision using an evolved recombinase. Science 316: 1912 Buchholz & Hauber (2011) In vitro evolution and analysis of HIV-1 LTR-specific recombinases. Methods 53: 102 Hauber et al. (2013) Highly significant antiviral activity of HIV-1 LTR-S Tre recombinase in humanized mice. PLoS Pathogens 9: e1003587 Karpinski et al (2014) Universal Tre (uTre) recombinase specifically targets the majority of HIV-1 isolates. J Int AIDS Soc 17: 19706.

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