“III. Background
A. Potential Risks of Delayed Adverse Events Following Exposure to Human Gene Therapy Products…
Characteristics unique to human GT [gene therapy] products that may be associated with delayed adverse events include: ...
3. Prolonged expression: A GT product where the transgene (therapeutic gene) encodes growth factors, such as vascular endothelial growth factor (VEGF) or proteins associated with cell division such as p53, may raise the potential for unregulated cell growth and malignancies due to prolonged exposure to the therapeutic protein. Similarly, transgenes encoding immune recognition factors may introduce the risk for autoimmune-like reactions (to self-antigens) upon prolonged exposure. For GT products that carry transcriptional regulatory elements (e.g., microRNA) or immune-modulatory proteins (e.g., cytokines) there is also the risk of unknown pleotropic effects, including altered expression of host (human) genes that could result in unpredictable and undesirable outcomes.
4. Latency: When the GT product has the potential for latency, such as a herpesvirus, there is the potential for reactivation from latency and the risk of delayed adverse events related to a symptomatic infection.
5. Establishment of persistent infections: GT products that are replication competent viruses and bacteria, such as listeria-based bacterial vectors, have the potential to establish persistent infections in immunocompromised patients leading to the risk of developing a delayed but serious infection.”