Lymphocyte antigen 6 complex locus A (Ly-6A) (Ly-6A)

Lymphocyte antigen 6 complex locus A (Ly-6A), widely known as Stem cell antigen-1 (Sca-1), is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein belonging to the Ly6/uPAR superfamily [1]. It is primarily expressed in mice and serves as a definitive marker for the identification and enrichment of hematopoietic stem cells (HSCs) [2]. Beyond its role as a biomarker, Ly-6A is involved in T-cell activation and the regulation of cell proliferation and differentiation within the immune system [3]. In recent years, Ly-6A has emerged as a critical target in gene therapy research due to its role as the primary receptor for engineered adeno-associated virus (AAV) capsids, such as AAV-PHP.B, which cross the blood-brain barrier (BBB) with high efficiency in specific mouse strains [4]. This interaction facilitates non-invasive delivery of genetic cargo to the central nervous system, although the lack of a direct human ortholog for Ly-6A limits the direct clinical translation of these specific vectors [5]. Consequently, while Ly-6A is a powerful tool for murine studies and proof-of-concept delivery systems, therapeutic applications in humans require the identification of analogous receptors in the human BBB [4, 5].

Other names

Sca-1Stem cell antigen-1TAPT-cell activating proteinLy-6A.2Ly-6E.1

Acts as a cell surface receptor for engineered adeno-associated virus (AAV) capsids to facilitate transport across the blood-brain barrier via receptor-mediated transcytosis.