Enable Patients With Anti-Capsid Antibodies for AAV8 or AAVrh.10 to Participate in Clinical Trials to Undergo Gene Therapy with AAV
These adeno-associate vector capsid variants offer antibody-escaping abilities that will enable patients with antibodies against an AAV serotype to receive therapy or participate in clinical trials anyway. Due to the high incidence of target diseases and increased funding for gene therapy research, the market for AAV-based gene therapy is expected to grow exponentially with a growth rate of 43 percent in the period from 2019 to 2030. Up to 40 percent of the population has antibodies that neutralize AAV8, excluding them from AAV gene therapy or clinical trials utilizing AAV8. Other patients have neutralizing antibodies against AAVrh.10 and other AAV serotypes naturally or due to previous treatment with an AAV vector.
Researchers at the University of Florida have modified AAVrh.10 vectors to create improved variants that can evade neutralizing antibodies against different AAV serotypes that are structurally similar to AAVrh.10, most notably, AAV8. The variants will allow more patients previously treated with an AAV vector or those positive for neutralizing antibodies against AAVrh.10 and AAV8 to be treated using AAV gene therapy.
Application
AAV capsid variants that evade neutralizing antibodies to AAVrh.10 and AAV8 in populations with antibodies to those serotypes, allowing more patients to receive gene therapy and participate in clinical trials.
Advantages
- Capsid variants of the AAVrh.10 vector with host antibody escaping properties, providing an alternative serotype for the treatment of patients previously treated with an AAV8 vector or who have neutralizing antibodies to AAVrh.10
- Retains sufficient structure similarity to wild type serotypes, providing effective function without an immune response
Technology
The structure-guided approach by UF researchers aims to develop an AAVrh.10 vector capsid variant with tissue targeting and antibody escape abilities. Based on the analysis, the variant escapes recognition by antibodies cross-reactive to AAV8 and AAVrh.10, while maintaining the wild-type infectivity. This offers the opportunity to patients who have these antibodies for acceptance into clinical trials or treatments. Information of the receptor-binding site shows the possibility for AAV tissue tropism engineering, guiding the creation of altered tissue targets.
