Transferrin receptor-targeting capsids
We have engineered a central nervous system (CNS)-targeting AAV capsid that binds to the human Transferrin Receptor 1 (TfR1)
Apertura’s TfR1 capsids can cross the blood-brain barrier (BBB) and deliver therapeutic cargo throughout the central nervous system (CNS) via systemic administration
Ubiquity and Specificity
Human TfR1 is broadly expressed across endothelium cells composing the blood vessels of the CNS. TfR1 is important for iron transport to the brain and spinal cord, which are robustly vascularized ensuring proximity to all cells, including neurons.
Enables Capsids to Cross the BBB
Via the TfR1, iron-bound transferrin is shuttled across the BBB through a process called receptor-mediated transcytosis. Apertura’s capsid binds to TfR1 without interfering with transferrin binding, resulting in receptor-mediated transcytosis of the capsid into the CNS.
Intravenous Delivery to the CNS
Because Apertura’s capsid crosses the BBB, it can be delivered by intravenous administration, a safer option than the current standards of direct injection into the brain or spinal cord.
Validated Biologic Target
TfR1 is already being exploited for CNS access by several biologic therapeutics that are approved and in clinical development.
Apertura’s human TfR1-targeted capsids cross the BBB, demonstrating broad distribution and transduction in both neurons and astrocytes while also reducing distribution of the capsids to the liver.
Apertura’s capsid holds tremendous promise as a gene therapy approach for patients with devastating neurological diseases.