2023 - Going Beyond the Blood-Brain Barrier: Delivery of Diverse Cargo to Targeted Cells Within the Central Nervous System

The blood-brain barrier is a set of specialized and highly selective cellular barriers that protects the central nervous system (CNS). While necessary under normal physiology, the blood-brain barrier prevents entry of many neurotherapeutics into the brain and biologic therapies such as antibodies and gene therapies are essentially excluded from the CNS.
SRI International has developed an unbiased screening platform to identify peptides that mediate delivery throughout the CNS without disruption of the blood-brain barrier or destruction of biological cargo. This approach, named DiaCyt (Dia: Through and Cyt: Cell), utilizes high diversity phage-displayed peptide libraries to peptides that transport cargos across a cellular barrier.
NODATA
The MTS can transport proteins and monoclonal antibodies into the CNS. The identified MTSs can access the CNS but have no affinity for cells of the CNS, thus intracellular delivery of cargos to these important cell types requires additional cell-targeting agents. Towards this goal, they have also identified cell-specific peptides for microglia and neuronal cells, capable of intracellular delivery of cargos. These peptides, referred to as molecular guidance systems (MGS), display cell-specificity for their target cell type and mediate rapid uptake resulting in intracellular concentrations that range from 100 nM to 1 µM. Combining the MTS and MGS peptides allows for both transport and cell-specific targeting within the CNS.
Register today to learn more about going beyond the blood-brain barrier through the delivery of diverse cargo within the central nervous system.