Terminal galactose (Gal)

Terminal galactose residues on N-linked glycans serve as the primary cell-surface attachment factors for the Adeno-associated virus rhesus isolate 10 (AAVrh.10) capsid. These glycans are ubiquitously expressed on various cell types, particularly in the central nervous system and liver, which facilitates the broad tropism of AAVrh.10-based gene therapy vectors [1]. The interaction occurs when the viral capsid's surface loops bind specifically to the terminal galactose moiety, triggering the internalization of the viral particle via endocytosis [2]. In a therapeutic context, these glycans are exploited as docking sites for recombinant AAV vectors delivering genetic cargo to treat conditions like Sanfilippo syndrome and Metachromatic leukodystrophy [3]. Understanding the density and distribution of these glycans is crucial for predicting the efficacy and biodistribution of AAVrh.10-mediated gene transfer [4]. Challenges include potential off-target effects due to the widespread presence of galactose and the influence of neuraminidase activity, which can expose more terminal galactose sites by removing sialic acid [5]. Furthermore, pre-existing neutralizing antibodies against the AAVrh.10 capsid can interfere with this binding process, limiting the patient population eligible for such therapies.

Other names

Terminal GalN-linked galactoseGalactose-containing glycansAAVrh.10 receptorTerminal beta-galactoseCell-surface glycans recognized by AAVrh.10 capsid

The AAVrh.10 capsid binds to terminal galactose residues on cell-surface N-linked glycans, facilitating viral attachment and subsequent receptor-mediated endocytosis for the delivery of therapeutic genetic material.