Our beautiful immune systems have evolved to efficiently recognise foreign objects – like bacteria and viruses – that aren’t supposed to be there. This activates a huge series of biological reactions that secure the threat and restore a safe environment.
Sometimes, though, the immune system reacts to things that it perceives as a theat, but are actually benign. This includes drugs and biotherapeutics that are being delivered to treat patients, but get blasted by immune responses before they get a chance to help.
Now, a team of scientists led by Chris King at the University of Washington in the USA have explored an interesting way to silence immune reactions against such foreign therapeutic proteins. They used computers to locate every immunogenic part of the protein (the T cell epitopes), and then predict a redesigned sequence that eliminated the immunogenicity but retained the protein activity.
They used this method to successfully redesign two model proteins (GFP and Pseudomonas exotoxin A), and in future studies will use this approach to create immune silent proteins like factor VIII, a therapeutic protein for haemophilia A patients.
Image: The crystal structure of the factor VIII protein, Jacky Chi Ki Ngo