In in vivo gene therapy, a vector (typically, a virus) is introduced to the patient, which then achieves the desired biological effect by passing the genetic material (e.g. for a missing protein) into the patients cells. In ex vivo gene therapies, such as CAR-T therapeutics, the patients own cells (autologous) or healthy donor cells (allogeneic) are modified outside the body (hence, ex vivo) using a vector to express a particular protein, such as a chimeric antigen receptor.
In vivo gene therapy is seen as simpler, since it does not require the harvesting of mitotic cells. However, ex vivo gene therapies are better tolerated and less associated with severe immune responses. The death of Jesse Gelsinger in a trial of an adenovirus-vectored treatment for ornithine transcarbamylase deficiency due to a systemic inflammatory reaction led to a temporary halt on gene therapy trials across the United States. , in vivo and ex vivo therapeutics are both seen as safe.