Disciplines
Biology (80%); Medical Biotechnology (20%)
Keywords
Adenovirus,
Infection,
CRISPR,
Cas9
Abstract
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.