Tolerization with a Novel Dual-Acting Liposomal Tim Agonist Prepares the Immune System for the Success of Gene...

Gene therapy holds great promise for treating various congenital rare diseases. However, immunogenicity against viral vectors used in gene therapy remains a challenge, impacting both the safety and efficacy of gene therapy products. Neutralizing antibodies against the vector capsid proteins impact the ability to re-dose patients, which a growing body of evidence suggests might be required for some indications and certain younger patient populations. In this communication, we report a novel dual-acting liposomal formulation that induces immune tolerance toward adeno-associated virus 9^null (AAV9^null) capsid proteins. We present in silico data on our first- and second-generation Tim agonist molecules as well as in vitro and in vivo data supporting the generation of antigen-specific regulatory T cells (Tregs) as well as abrogation of antibody response to AAV9^null capsid in our animal models. These early data are encouraging and may offer a new solution to mitigate the immunogenicity induced by gene therapy products.