Points to consider for non-clinical safety evaluation of <i>in vivo</i> gene therapy products

Abstract

Advances in gene therapy have led to a wide range of gene therapy products. Hence, it is challenging to use standard non-clinical safety tests, which are typically used to evaluate chemically synthesized products. Therefore, a case-by-case safety evaluation based on the unique characteristics of each product is necessary. In Japan, the fundamental considerations for evaluating the non-clinical safety of gene therapy products are outlined in “Ensuring the Quality and Safety of Gene Therapy Products”. Notably, when designing non-clinical safety studies, it is essential to consider factors such as the efficiency of vector transduction, tissue/cell tropism of the vector, and species differences in the expression level and biological activity of transgene products in the target tissue/organs. However, it is also crucial to understand the limitations of animal studies that arise due to species differences and to assess the safety of expression vectors and expressed genes based on a thorough literature review of their biological properties. The aims of this review are to present non-clinical safety evaluation approaches for gene therapy products as outlined in the Japanese guidelines and key considerations for appropriate non-clinical safety evaluation of in vivo gene therapy products.