An AAV-based vector delivery system for delivering the gene cassette
Best-in-Class AAV-based Vector Delivery System
We deliver the gene cassette to the target tissue using an engineered, non-replicating viral vector delivery system based on AAV (adeno-associated virus). Researchers have used AAV-based vectors in pre-clinical research and over 80 clinical trials in which AAV-based vectors have demonstrated a good safety profile. AAVs have also demonstrated lasting therapeutic gene expression following a single treatment in preclinical and clinical studies.
We use the AAV5 variant, or serotype, of vector in our product candidates in hemophilia B and Huntington's disease, and have exclusive, worldwide rights to AAV5 for use in therapeutic products delivered to the brain or liver. Our research suggests that a greater portion of patients can be effectively treated with AAV5 gene therapy, compared to other AAV-based gene therapies.
AAV5-based gene therapies have been demonstrated to be safe and well-tolerated in a multitude of clinical trials, including five uniQure trials conducted in nearly 80 patients in hemophilia B and other indications. No patient treated in clinical trials with the uniQure’s AAV5 gene therapies has experienced any confirmed cytotoxic T-cell-mediated immune response to the capsid. Additionally, pre-clinical and clinical data show that AAV5-based gene therapies may be viable treatments in patients with pre-existing antibodies to AAV5, thereby potentially increasing patient eligibility for treatment compared to other gene therapy product candidates.
One of the major challenges in AAV-based gene therapy is the presence of circulating anti-AAV neutralizing antibodies, which can pre-exist in patients and may prevent successful gene transfer. We have presented preclinical data demonstrating successful and effective transduction of AAV5 in non-human primates with pre-existing anti-AAV5 neutralizing antibodies (NABs). At all observed levels, pre-existing neutralizing antibodies for AAV5 did not have a negative impact on the transduction effectiveness of the AAV5 vector. This suggests a much broader potential population of eligible patients than previously expected for AAV5-based gene therapies, as it appears that patients with pre-existing anti-AAV5 NABs may still be able to be successfully treated with AAV5 gene therapies.
High levels of circulating anti-AAV neutralizing antibodies can develop after a single administration of gene therapy and can prevent successful gene transfer in patients. We have made tremendous progress in optimizing and advancing re-administration and cross-administration protocols that we believe will significantly impact the application of our gene therapies and potentially enable repeated administration. We have presented preclinical data demonstrating successful re-administration of gene therapy with our AAV5 vector following a proprietary immunoadsorption procedure in non-human primates (NHPs). In addition, we have published data demonstrating successful cross-administration of gene therapies in NHPs using sequential administration of AAV5 and AAV1 vector serotypes, suggesting that cross-administration of AAV5 gene therapies with other vectors may be possible in humans.
AAV5 is a highly differentiated, best-in-class vector with the potential to more effectively and safely deliver gene therapies to a greater portion of patients in need of treatment.