Gene Hackers Resurrect Ancient Virus, Create Powerful Gene Therapy Vector
Scientists at at Massachusetts Eye and Ear and Schepens Eye Research Institute have resurrected an ancient virus, and found that the virus is highly effective at delivering gene therapies to the liver, muscle, and retina. This discovery could potentially be used to design gene therapies that are safer and more potent, and have a wider reach, than therapies currently available.
The discovery is published July 30 in Cell Reports with the title “In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector.” The research paper is freely available online.
“We believe our findings will teach us how complex biological structures, such as AAVs (adeno-associated viruses), are built,” said Assistant Professor of Ophthalmology and Associate Director of the Ocular Genomics Institute Luk H. Vandenberghe.
From this knowledge, we hope to design next-generation viruses for use as vectors in gene therapy.
Synthetic Ancient Viruses Built in the Lab Deliver Gene Therapy to Mice
To survive, a virus must infiltrate a host organism undetected and transfer its genetic material into the host’s cells, where it will use the host to replicate and proliferate. Therefore, a virus modified to carry therapeutic genes can be an ideal delivery system for gene therapy.
It’s important to use a virus that is not recognized as harmful by the immune system, which otherwise would try to destroy the virus before it completes its therapeutic action. Engineering new, benign viruses could render the viruses unrecognizable and increase the number of people for whom a given gene therapy will work. However, engineering a new virus with desired properties from scratch is a very complex endeavor.
The researchers were able to trace evolutionary genetic changes in Adeno-Associated Viruses (AAV), a gene-delivery platform with demonstrated safety and efficacy, back to remote ancestors. Then, the researchers could build in the laboratory nine synthetic ancient viruses. When injected into mice, the most ancient, called Anc80, successfully targeted the liver, muscle, and retina, without producing toxic side effects.
“The ancestral reconstruction of Anc80L65, the common putative ancestor of AAV1–3 and 7–9, yielded a highly potent vector particle with potential use in gene therapy applications via in silico and synthetic biology methods,” concludes the researchers, and add that the development may eventually facilitate structure-based design of this potential new class of genetic drugs. Vandenberghe said:
The vectors developed and characterized in this study demonstrate unique and potent biology that justify their consideration for gene therapy applications.
Vandenberghe added that future related research will continue to seek improved vectors for clinical applications.
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