The engineered AAV2-HBKO promotes non-invasive gene delivery to large brain regions beyond ultrasound targeted sites.

Magnetic resonance imaging-guided focused ultrasound combined with microbubbles injected in the bloodstream (MRIgFUS) temporarily increases the permeability of the blood-brain barrier (BBB), which facilitates the entry of intravenously administered adeno-associated viruses (AAVs) from the blood to targeted brain areas. To date, the properties of the AAVs used for MRIgFUS delivery resulted in cell transduction limited to MRIgFUS-targeted sites. Considering future clinical applications, strategies are needed to deliver genes to multiple locations and large brain volumes while creating minimal BBB modulation.

Efficacy of gene delivery to the brain using AAV and ultrasound depends on serotypes and brain areas.

Focused ultrasound combined with intravenously injected microbubbles (FUS) is known to non-invasively, locally, and transiently increase the permeability of the blood-brain barrier (BBB). A promising approach for non-invasive gene delivery to the brain is to administer recombinant adeno-associated viruses (AAVs) intravenously and allow them to cross the BBB at precise FUS-targeted brain regions. FUS-AAV delivery has been achieved in animal models; however, the key elements influencing, guiding, and monitoring the success of FUS-AAV delivery to the brain remain largely unknown.