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. 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.
Short interfering RNAs (siRNAs) and artificial microRNAs (amiRNAs) are a class of artificial small RNAs that can bring about the inactivation of cellular and viral genes via the RNA interference (RNAi) pathway. In a previous project led by Dr. Reinhard Klein highly potent siRNAs and amiRNAs with activity against components of the adenoviral DNA replication machinery that can effectively inhibit the replication of human adenoviruses in cell culture experiments were developed and characterized.
The project is aimed at investigating if adenovirus infections can be inhibited by these RNAi-triggering small RNAs in vivo, and which of the two approaches (i.e. siRNA versus amiRNA) is more effective. RNAi-based inhibition of adenoviruses is assessed in the Syrian hamster model which is able to mimic adenovirus infections in immunodeficient humans. Moreover, one of the two small RNA-based approaches is anticipated to lead to the selective amplification of the RNAi-triggering RNAs in adenovirus-infected cells and their transfer to neighbouring cells where they are supposed to inhibit the otherwise uncontrolled multiplication of spreading adenoviruses.
The project is funded by the Austrian Science Fund (FWF).