Biodistribution is defined as the distribution of a therapeutic substance in various tissues and organs of an organism. While biodistribution analysis is a very standard and common process for investigating novel small molecule therapies, it is more complicated for cell and gene therapy products. In gene therapy, biodistribution analysis is performed to determine the in vivo distribution and the persistence of the viral vector in target and non-target tissues, body fluids and organs following administration in animals. Another assessment is viral shedding which is define as the dissemination of the virus (most commonly AAV vector) via body excretions. The detection of viral biodistribution and shedding is a critical assessment of safety of the gene therapy product.
The FDA recommends biodistribution studies for the following category of gene therapy (GT) products prior to human studies:
- Investigational GT products that belong to a new vector class.
- Established vectors with significant changes in the vector backbone.
- Established vectors with a significant formulation change.
- Established vectors with a significant change in the ROA.
- Established vectors with a significant change in the dosing schedule and/or the vector dose levels.
Applied StemCell (ASC) has extensive experience in gene therapy biodistribution studies involving many different species of animals and AAV serotypes. Using technical expertise in various PCRs (qPCR, ddPCR, RT-PCR), NGS and Sanger Sequencing, we can quantitate the viral copy numbers in DNA samples extracted from animal tissue and body fluids, as well as transgene expression levels. Assays will be custom developed and validated for each gene therapy product and AAV serotype to enable clear understanding of the therapeutic candidate and therefore vital decisions in the drug development process.