Adeno-associated virus rhesus isolate 10 capsid (AAVrh.10) (AAVrh.10)

The Adeno-associated virus rhesus isolate 10 (AAVrh.10) capsid is a protein shell derived from a rhesus macaque AAV serotype, widely utilized as a vector in gene therapy (Gao et al., 2002). It is composed of three structural proteins (VP1, VP2, and VP3) that assemble into an icosahedral structure to protect and deliver a therapeutic genetic payload (Piguet et al., 2017). AAVrh.10 is particularly noted for its robust tropism for the central nervous system and liver, making it a primary candidate for treating neurodegenerative and metabolic disorders like Metachromatic leukodystrophy (Rosenberg et al., 2014). However, its efficacy is significantly challenged by pre-existing neutralizing antibodies (NAbs) in the human population, which can bind the capsid and prevent cellular entry (Leborgne et al., 2020). Human intravenous immunoglobulin (IVIG) is frequently used in research to model this inhibitory effect, as it contains a pool of antibodies that cross-react with the AAVrh.10 surface (Mimuro et al., 2014). Strategies to overcome this barrier include the use of IgG-cleaving enzymes like imlifidase or plasmapheresis to temporarily deplete the circulating antibodies before vector administration (Leborgne et al., 2020). This target is critical for the development of "off-the-shelf" gene therapies that can be administered to patients regardless of their serostatus.

Other names

AAVrh10AAV-rh10Rhesus monkey-derived AAV serotype 10AAV serotype rh.10

AAVrh.10 acts as a viral vector that encapsulates a therapeutic DNA expression cassette, facilitating its delivery into target cells by binding to specific cell surface receptors and undergoing endocytosis. Drugs like imlifidase target and degrade the neutralizing antibodies that would otherwise bind to and clear the AAVrh.10 capsid, thereby enabling successful transduction in the presence of pre-existing immunity.