Focused ultrasound (FUS) combined with microbubbles (MBs) is a cutting-edge technology
for local, safe, and transient BBB opening. While the innate blood-brain barrier (BBB) poses
a major obstacle in the delivery of therapeutics to the brain, normally excluding drugs sized
0.4 kDa or greater, BBB opening with FUS+MB can be optimized for maximized drug
delivery of larger molecules. This can especially be utilized for the delivery of lipid
nanoparticles (LNP), which are highly investigated therapeutics in the field of cancer.
Glioblastoma Multiforme (GBM) is the most aggressive brain malignancy, with a median
survival of ~15 months after surgery combined with chemotherapy or radiation, mainly due
to high recurrence rate and the development of drug resistance. Hence, there is a desperate
need for new therapeutic approaches for this devastating disease.
We aim to develop a therapeutic platform for GBM, by combining BBB opening together
with systemic administration of unique mRNA-LNPs encapsulating the mRNA of the
proinflammatory cytokine IL7 (mIL7-LNPs). The expressed protein would function as
immunotherapy against the brain tumor, and shrink it in a non-invasive manner. This can lead
the path to a new US-based technology for brain noninvasive GBM therapy, or other brain
diseases where the BBB forms a major obstacle for drug delivery.
