A bioanalytical assessment strategy needs to be in place to address the complex challenges of immunogenicity to gene therapy vectors and transgenes. The gene therapy using viral vectors aims to deliver corrected version of gene to stem cells, tissues and immune cells to target single gene mutations, target defective cells within tissues and target tumors through viral vectors that can promote oncolysis. The main challenges with these approaches include immune responses to the viral and transgene proteins. Hence the humoral and cellular immune response needs to be assessed along with any nucleic acid related priming of the immune system The bioanalytical assays have to either be adapted from our knowledge of vaccine assays or modified to provide a better understanding of the immune response to both vector and transgene. Additionally, the shedding and biodistribution will require amplification of virus signal based on the site of administration.
Viral Vectors based Gene Therapy (AAV and Oncolytic viral vectors )
2. Bioanalytical Assays and their Consideration
Neutralizing Ab assay/Pre-existing Ab
Biodistribution and shedding
Regulatory concerns and guidance
Recommendations for enzyme assays and their characterization, and life cycle management