The pre-clinical study led by Genethon demonstrated that co-administration of synthetic vaccine particles encapsulating rapamycin (“SVP-R”) with adeno-associated virus (“AAV”) gene therapy vectors induced safe and effective mitigation of immune responses against the capsid in an antigen-selective manner. This resulted in safe and efficient vector re-administration in both small and large animal models of hepatic gene transfer.
Immunogenicity of AAV viral vectors has been a major roadblock to vector re-administration which may be required to ensure the durability of gene therapy, particularly for systemic and pediatric applications.
For many inherited metabolic and degenerative diseases, early morbidity and mortality requires treatment early in life prior to the onset of irreversible tissue damage. However, expression of the therapeutic transgene is expected to wane over time as pediatric patients grow. Maintaining the ability to re-administer viral vectors such as AAV may therefore be essential to achieve sustained therapeutic efficacy over time.
“Despite exciting therapeutic results achieved to date with AAV-mediated gene therapy, development of antibodies against the vector, hampering efficient re-administration, represents potential obstacles for long-term efficacy of the treatments.” said Frédéric Revah, Ph.D., CEO of Généthon. “Safe and effective strategies that reduce AAV vector immunogenicity and allow for stable transgene expression and redosing are urgently needed to allow continued advancement of the field. Co-administration of AAV vectors and SVP-R represents a potentially powerful strategy to address this long-standing challenge by modulating vector immunogenicity and enabling vector re-administration in mice and non-human primates, as was shown in the published study.”