Host neutralizing antibodies against AAV-PR capsid proteins (Anti-AAV-PR NAbs)

Host neutralizing antibodies against AAV-PR capsid proteins are a specific subset of the humoral immune response that recognizes and binds to the engineered AAV-PR viral vector. AAV-PR is a specialized adeno-associated virus variant, derived from the AAV9 serotype with a PRPPSTH peptide insertion at position 588, designed for high-efficiency transduction of vascular smooth muscle cells and cerebral pericytes (McCarthy et al., 2023). These neutralizing antibodies (NAbs) pose a significant challenge to gene therapy, as they can bind to the viral capsid in the systemic circulation, preventing the vector from reaching its target tissues or entering cells. In clinical and preclinical settings, the presence of these antibodies often serves as an exclusion criterion for treatment or necessitates the use of clearing strategies such as IgG-cleaving enzymes (e.g., imlifidase) or plasmapheresis. Managing these antibodies is critical for the successful delivery of genetic payloads, such as CRISPR-Cas9 base editors, for treating multisystemic smooth muscle dysfunction syndrome (MSMDS) and other genetic vasculopathies (Alves et al., 2024).

Other names

Anti-AAV-PR antibodiesNeutralizing antibodies against AAV-PRHost antibodies to AAV-PRAnti-AAV-PR neutralizing antibodies

Proteolytic cleavage of IgG (Imlifidase), physical removal of antibodies (Plasmapheresis), B-cell depletion (Rituximab), and plasma cell inhibition (Bortezomib).