Low-density lipoprotein receptor (LDLR) family and Sialic acid (LDLR/LRP1/Sialic acid)

AAV-Ep+ is a next-generation adeno-associated virus (AAV) capsid variant engineered for high-efficiency gene delivery to the central nervous system (CNS), specifically targeting ependymal cells and neurons. Developed by Latus Bio and researchers at the Children's Hospital of Philadelphia, AAV-Ep+ utilizes specific cell-surface receptors and glycans for entry, with recent evidence identifying members of the low-density lipoprotein receptor (LDLR) family, such as LDLR and LRP1, as key mediators of its potent transduction. By targeting the ependyma, AAV-Ep+ enables the creation of "protein factories" that secrete therapeutic enzymes into the cerebrospinal fluid (CSF), providing a broad distribution of treatment for neurodegenerative and lysosomal storage disorders like CLN2 disease. The capsid's entry mechanism also involves interactions with sialic acid glycans, inherited from its parental AAV1 serotype, which facilitate initial attachment and subsequent receptor-mediated endocytosis. This dual-receptor mechanism allows AAV-Ep+ to achieve superior transduction levels at significantly lower doses compared to traditional AAV vectors, potentially reducing systemic toxicity and improving therapeutic outcomes in CNS-directed gene therapies.

Other names

Low-density lipoprotein receptorLow-density lipoprotein receptor-related protein 1LRP1LDLRSialic acidAlpha-2,3-linked sialic acidAlpha-2,6-linked sialic acidAAV-Ep+ receptor

Receptor-mediated endocytosis and viral entry