|The Anc80 virus delivers genes to the mouse retina that fluoresce green when expressed. Pictured here, the delivered genes are active in the retina's color-detecting cells.--Courtesy of Harvard|
Researchers at the Harvard Stem Cell Institute (HSCI) have built a viral vector based on an ancient virus that is highly effective at delivering gene therapies to the liver, muscle and retina. The findings may allow the use of viruses as a safe and more potent method for gene therapy.
The application of gene therapy using viral vectors to insert therapeutic molecules of DNA has had considerable attention in recent years. Using viruses as a courier for targeted gene therapy has many applications--and there's been a burst of new gene therapy startups in the biotech world--but its progress has been hampered by safety and efficacy issues in the clinic.
Recent work driven by Luk Vandenberghe at Massachusetts Eye and Ear at HSCI was published in Cell Reports. "We believe our findings will teach us how complex biological structures such as AAVs [adeno-associated viruses] are built," says the senior author. "From this knowledge, we hope to design next-generation viruses for use as vectors in gene therapy."
AAVs have been well studied as a vector of choice. However, if the patient has been exposed to these before--as they are naturally occurring throughout the human population--then their immune system will recognize and dispose of it. Vandenberghe's team is working to overcome this by developing new viruses capable of going undetected and in doing so, increase the number within a population who will benefit from gene therapy.
The difficulty of engineering these vectors lies within the complex structure of the AAV. By studying the evolutionary history of the virus, the team catalogued the structural changes of the virus and built nine new synthetic ancestor viruses.
The oldest recreated virus, called Anc80, was then injected into mice and targeted the liver, muscle and retina with no side effects.
"The vectors developed and characterized in this study demonstrate unique and potent biology that justify their consideration for gene therapy applications," Vandenberghe said.