Apertura Gene Therapy Reveals Newly Engineered AAV Capsids Tailored for Human Transferrin Receptor 1 in Advancing Neurological Gene Therapy Delivery
Friday, January 05, 2024
Apertura Gene Therapy, a biotechnology company, has introduced its proprietary engineered Adeno-Associated Virus (AAV) capsids designed to target the human Transferrin Receptor 1 (TfR1). This technology aims to facilitate the traversal of the blood-brain barrier (BBB), allowing for effective gene therapy delivery throughout the central nervous system (CNS) to address diseases with limited treatment options.
The human TfR1, found extensively in brain capillary endothelium, plays a crucial role in mediating iron transport across the BBB. The BBB, a protective layer of endothelial cells, poses challenges for drug development in treating neurological disorders due to its selective nature. Apertura's TfR1 capsids, developed in collaboration with Dr. Ben Deverman's Vector Engineering Lab at the Broad Institute of MIT and Harvard, bind to the apical domain of TfR1, enabling receptor-mediated transcytosis into the CNS without hindering transferrin binding. Administered intravenously, these second-generation capsids efficiently cross the BBB, displaying widespread distribution and transduction in neurons and astrocytes while minimizing distribution to the liver. Notably, Apertura's TfR1 capsids achieve this with significantly lower dose levels compared to existing CNS-targeted gene therapies.
Joseph La Barge, CEO of Apertura, highlighted the significance of this achievement, emphasizing that the capsids represent a groundbreaking approach in gene therapy design. Engineered through their native structure to target TfR1, these capsids mitigate the historical challenges associated with AAV capsid engineering and demonstrate potential for treating currently intractable CNS diseases. Apertura is leveraging this technology to advance its pipeline of next-generation gene therapies for various genetic diseases.
Established in 2021, Apertura employs an integrated, machine learning-enabled, data-driven strategy to enhance gene expression and delivery. The company is actively progressing two undisclosed neurologic condition programs using its TfR1 capsids and applying its platform technologies to engineer novel payloads for genetic expression regulation, along with developing additional AAV capsids targeting specific human receptors.
Source: businesswire.com
