Terminal galactose-bearing cell-surface glycan (Terminal galactose)

Terminal galactose-bearing cell-surface glycans serve as the primary attachment receptors for Adeno-associated virus serotype 9 (AAV9), a prominent vector used in gene therapy. The AAV9 capsid specifically interacts with N-linked glycans that terminate in galactose, a binding mechanism that is essential for the virus to enter host cells (Shen et al., J. Virol. 2011). This interaction is particularly significant in medicine because AAV9 has the unique ability to cross the blood-brain barrier, making it a preferred vehicle for treating central nervous system disorders (Bell et al., J. Virol. 2011). Therapeutic agents like Onasemnogene abeparvovec (Zolgensma) leverage this binding to deliver corrective genes for spinal muscular atrophy. While highly effective for delivery, the ubiquity of these glycans and the prevalence of AAV9 in the environment can lead to pre-existing immunity, which may neutralize the therapy before it reaches the target tissue. Additionally, high systemic doses required for efficacy can lead to significant safety concerns, including liver injury and immune-mediated inflammatory responses (Mendell et al., N. Engl. J. Med. 2017).

Other names

AAV9 receptorN-linked terminal galactoseGalactose-bearing glycansAAV9 binding glycan

The AAV9 capsid binds to terminal galactose residues on cell-surface glycoproteins or glycolipids, facilitating viral attachment and subsequent internalization via endocytosis for the delivery of therapeutic genetic material.