Abstract
Abstract
While the blood–brain barrier (BBB) is critical for maintaining the microenvironment of the central nervous system (CNS), it simultaneously acts as a bottleneck for successful delivery of the majority of therapeutics into the brain. Low intensity focused ultrasound (FUS) combined with systemically delivered microbubbles (MBs) has already been employed to transiently open the BBB in a spatially-restricted manner to enhance the delivery of therapeutics into the brain, including recombinant adeno-associated viruses (rAAVs), antibodies, nanoparticles, or small interfering RNAs. In this study we demonstrate the feasibility to enhance the delivery of systemically administered fluorescently-labeled antisense oligonucleotides (ASOs) into the murine striatum using magnetic resonance imaging (MRI) targeted FUS. We focused only on the acute biodistribution 30 min post-sonication and did not evaluate target knockdown or long-term safety. Immunohistological analysis revealed that majority of medium spiny neurons within the sampled sonicated striatal region were positive for the ASO. Absolute tissue quantification via LC-MS confirmed these findings, revealing a substantial increase in target tissue concentration. Taken together, these results suggest MRI-targeted FUS as a promising non-invasive technology to enhance the delivery of naked ASOs into deep structures of the brain.