2025 Volume 42 Issue 3 Pages 226-229
In prion diseases, normal prion protein is transformed into the abnormal protein which propagates and accumulates in the brain, rapidly leading to neurodegeneration. The therapeutic strategy of normal prion gene knockdown in the brain using nucleic acid drugs is expected to be an effective disease modifying therapy from the early clinical stages. In fact, antisense oligonucleotide drugs, the most prevalent type of nucleic acid drugs, have begun to be utilized in a clinical trial.
A major challenge in the treatment of brain diseases using nucleic acid drugs is the requirement for frequent and invasive intrathecal administration. An ideal solution would involve the systemic administration of nucleic acid drugs, enabling their delivery into the brain across the blood–brain barrier (BBB).
Here we introduce two types of our original BBB–crossing drug delivery system. One is a nano engineering–based system for a variety of drug modalities, that allows the delivery through the transcellular route of brain microvascular endothelial cells, the chief components of the BBB, in response to the change in blood glucose concentration. The other system is a recombinant peptide–based system, that modulates the tight junctions at the points where the corners of three brain microvascular endothelial cells meet, allowing the delivery of antisense oligonucleotide through the paracellular route into the brain.
