CMV-iGluSnFR AAV (Serotype 9)

Since 1984, when recombinant adeno-associated virus (rAAV) serotype 2 was designed and first successfully used as a gene transfer vector, numerous other rAAV serotypes have been isolated and characterized. While many of these viruses demonstrate robust transduction efficiencies in various organ systems throughout the body via simple systemic delivery methods, widespread transduction of the central nervous system (CNS) via relatively noninvasive methods has been elusive. The well-established blood-brain barrier (BBB) ​​serves as a protective barrier that excludes potentially harmful molecules and microorganisms based on size, charge, and lipid solubility. Thus, the BBB effectively blocks the spread of rAAV to the CNS.

However, Foust and colleagues may have taken an important step toward the goal of systemic gene delivery to the CNS using rAAV in their recent report. In this exciting study, peripheral intravascular (i.v.) injections of rAAV9 into newborn or adult mice resulted in widespread transduction of the spinal cord or brain. Furthermore, rAAV has historically been shown to have extremely limited transduction of non-neuronal cells of the CNS. However, in this study, a significant fraction of non-neuronal cells in the brain and spinal cord were infected, depending on the age of the injected animals. Therefore, the findings of Foust et al. may have important clinical implications, as they will expand the scope of rAAV delivery to other cell types in the central nervous system that have been inaccessible to date.