Published in Scientific Reports: An adeno-associated virus (AAV) stably integrated into the DNA of large-footed Australian marsupials millions of years ago. Its evolutionary imprints were now discovered by scientists from the US and Australia*, and potentially could provide a new tool for translational and clinical applications.
For the first time researchers have demonstrated sequences of this type of virus in marsupials, which were found integrated in the genome of Macropodiformes - large-footed marsupials such as kangaroos and wallabies.
These 'endogenous viral elements' present a genetic record of an ancient virus, which between 45 and 27 million years ago became part of the genetic makeup of an ancestral marsupial. It then was passed on from generation to generation, leaving an evolutionary trace otherwise not available from viruses as they do not leave fossil records.
By studying their family tree and the viral DNA sequences from these different species, the researchers reconstructed the DNA sequence of the AAV that existed tens of millions of year ago.
Remarkably, it remained restricted to species within the Macropodiformes, so did not spread to other kinds of marsupials. The virus also remained relatively conserved in structure.
As well as providing new insight into the evolution of AAVs, their discovery could also be of interest for health and medical research.
AAVs are very efficient at getting therapeutic genes into target organs, yet are widely considered not to cause disease in mammals, including humans.
Different AAVs are specific for different cells and tissues in humans (a property known as “tropism”), and new AAVs are required to successfully aim at tissues over and above the main current targets, namely the central nervous system, the eye and the liver.
The discovery could thus provide new tools for the development of gene therapies.
*Australian researchers taking part in the study were from the Children’s Medical Research Institute, the Children’s Hospital at Westmead, the University of Sydney and La Trobe University