Hybrid phages, consisting of cis-elements from adeno-associated viruses and a single-stranded bacteriophage, have been used for ligand-directed tumor targeting, selectively killing tumor cells in mice in vivo.

Since it has been shown that these hybrid phages are able to kill eukaryotic cells selectively, they might be suitable for fighting parasites in or on their host organism, without attacking and damaging the host itself. In our project for the iGEM competition, we are planning to construct hybrid phages by heterologous gene expression in Escherichia coli. Furthermore, we are aiming to use selective endocytosis mechanisms as well as highly specialized CRSISPR- or toxicity systems to induce celldeath of unicellular parasites.

As possible model organisms to examine the implementation of hybridphages for this application, we intend to use Trypanosoma brucei, the pathogen causing the sleeping sickness, and Puccinia graminis, a parasite of grains, causing stem rust.

The sleeping sickness, also known as African trypanosomiasis is a disease caused by protozoa of the species T. brucei. It is usually transmitted via the bite of an infected tsetse fly. Treatments available for this disease have a low efficiency and cause major side effects like blindness, nerve damage, myelotoxicity or death.

Wheat stem rust is an infection of wheat or other varieties of grain, leading to lower crop yield and harvest losses up to 100%. It is caused by the parasitic fungus P. graminis. Previously, plants were modified to be resistant for these infections, but several P. graminis varieties overcame this resistance. One of these, Ug99, has been discovered in Uganda in 1998. According to estimates, approximately 90% of all wheat varieties are sensitive to Ug99, causing it to endanger food supplies in several countries in Africa and the middle east where it has been detected so far.