The U.S. Food and Drug Administration just approved a virus-based therapy for cancer. It is the first ever virus-based therapy approved, but it won't be the last.
Viruses as a treatment for cancer and other genetic disease will soon be the norm because of their ability to both easily gain access to the inside of cells and manipulate a cell's genome. However, finding the right virus is a tricky game but researchers believe they may have found a treat.
One vector that is currently increasing in popularity is the adeno-associated virus (AAV). Unlike the related adenovirus, which causes respiratory infections, there is no known disease that is caused by AAV. Despite its lack of pathogenicity, it infects human cells very effectively, while only invoking a very mild response from the immune system. Studies have shown that it can enter a diverse line of cells including pancreatic, liver, retina and muscle. It also enters both dividing and non-dividing cells.
However, there still exists a limited understanding of the virion's structure, hindering researchers ability to engineer an improved vector. Furthermore, one hurdle for employing AAV as a vector is that up to 90 percent of people produce antibodies to an AAV strain, thus making gene therapy with AAV less than ideal for the majority of the population.
In an attempt to better overcome these obstacle, Dr. Luk Vandenberghe s group at Harvard used computer based models to reverse-evolve to determine the now-extinct ancestral lines of AAV. Then they created these predecessors in order to test their ability to infect mammalian cells.
In short, they brought a virus back from the dead...a zombie virus if you will.
The results, published in Cell Reports, revealed that the oldest putative ancestor, Anc80, worked as well if not better than a commonly used AAV strain. The ancestral strain was able to express a transgene in retinal, skeletal, and liver cells of a mouse.
The advantage of bringing a strain back from extinction is that the immune system of modern humans would not have mounted a memory response to that vector. In a sense, scientists brought Anc80 back from extinction, making it highly unlikely that a person s immune system would have experienced a challenge from this strain.