Should patients with pre-existing anti-AAV antibodies be excluded from receiving intrathecally delivered AAV vectors?

Pre-existing neutralizing antibodies (NAbs) to adeno-associated virus (AAV) remain one of the largest practical barriers to limit the availability of gene therapy treatments to patients.1,2 Most AAV-based gene therapy clinical trials exclude patients with pre-existing anti-AAV NAbs. Although this is highly justified for AAV-based treatments delivered intravenously (i.v.), there has been an outstanding question of whether this exclusion should be in place for other routes of administration, such as direct intraparenchymal injection, subretinal injection, or intrathecal (IT) administration.