Gene therapy may warrant long-term follow-up of research subjects due to the risk of delayed adverse events. The FDA cites potential risks of adverse outcomes following exposure to human gene therapy products that are summarized as follows1:

“Integration activity” of the gene therapy product: Raises the potential for disruption of critical host genes that could result in malignancies.

Genome editing activity: Genome editing-based products impart their biological activity through site-specific changes in the human genome, but may also have off-target affects that raise the risk of malignancies and impaired gene function.

Prolonged expression: A gene therapy product where the therapeutic gene encodes growth factors, raising the potential for unregulated cell growth and malignancies.

Latency: A gene therapy product using, for example, a herpesvirus, has the potential for reactivation from latency, raising the risk of delayed adverse events related to a symptomatic infection.

Establishment of persistent infections: Gene therapy products that are replication-competent viruses and bacteria, such as listeria-based bacterial vectors, have the potential to cause persistent infections in immunocompromised patients.


1. FDA. Long-Term Follow-Up After Administration of Human Gene Therapy Products. Draft Guidance for Industry. July 2018. Available at: