Inhibitation of adenovirus replication by CISPR/Cas9

Patients with an impaired immune system such as HIV-positive individuals or solid organ and particularly hematopoietic stem cell transplant recipients are at high risk of undergoing life- threatening infections with human adenoviruses. Among stem cell transplant recipients with systemic infections mortality rates almost as high as 80% have been reported. The efficacy of commonly used drugs to treat adenovirus infections is limited and frequently associated with toxicity. Alternative drugs are still under investigation. Hence, given the fact that numbers of solid organ and hematopoietic stem cell transplant recipients are constantly rising, alternative treatment options are highly needed. The project is aimed at investigating if adenovirus infections can be inhibited by CRISPR/Cas9 in vitro and in vivo. CRISPR/Cas9 is a technology that can be used to inactivate cellular and viral genes. Inactivation of essential viral genes is expected to inhibit the multiplication of the virus. The project aims at inactivating the adenoviral E1A gene whose function is to modify the host cell in a way to generate an environment in which the virus is able to multiply. Moreover, the project aims at investigating if concomitant inhibition of viral DNA replication by conventional methods can aid in the inactivation of the viral genome by CRISPR/Cas9. The results generated in this project could possibly lay the fundament for the future development of an anti-adenoviral therapeutic strategies which may improve the treatment options directed against life-threatening adenovirus infections that are refractory toward conventional therapy.