Purdue University researchers successfully eliminated the native infection preferences of a Sindbis virus engineered to target and kill cancer cells, a milestone in the manipulation of this promising viral vector.
“This virus had been known to be a good vector for delivering therapeutic cargo, however it naturally infected all kinds of cells, and these diversions would compete with what we were instructing it to target,” said Richard Kuhn, the Gerald and Edna Mann Director of Purdue’s Bindley Biosciences Center. “We have now overcome a major challenge by not only inserting a targeting molecule of our choice, but also successfully stripping the virus of its native entry preferences. This was a big step in unlocking the potential of developing this virus into a platform for both targeted drug delivery, where it would sneak drugs inside cancer cells, and oncolytic virotherapy, where the virus itself destroys cancer cells.”
The achievement also demonstrates the ability to use methods of manipulation previously only applied to proteins. The team combined the methods of rational design, in which certain portions of the virus were strategically altered based on known information about their structure and function, and directed evolution, in which random mutations were introduced to millions of copies of the virus and the results are then screened for the desired traits, he said.
“These experiments demonstrate that these two methods can be combined and used to create complex molecular machines, like this viral vector with a tailored targeting receptor,” said Kuhn, who also is head of the Department of Biological Sciences. “We’ve now reached the point where we can easily change the virus to carry a variety of cargos and to seek out specific types of cells. We know where and how to add the characteristics we want and eliminate those that we do not.”