From ex vivo to in vivo: Shaping the next generation of viral vector manufacturing

Recent years have seen a major industry shift from ex vivo to in vivo viral vector delivery, driven by the need for scalable, cost‑effective, and more accessible gene and cell therapies.

In ex vivo approaches (e.g., autologous CAR‑T), cells are removed, genetically modified with viral vectors, and then reinfused; here the vector is a manufacturing tool, and residual impurities can be washed away from the final cell product. In contrast, in vivo therapies deliver the viral vector directly into the patient, so the vector itself is the drug and must meet stringent biologic‑grade purity and safety standards.

This shift is transforming viral vector manufacturing:
in vivo production requires much larger doses (scaling bioreactors from roughly 200 to up to 2,000 liters), stricter control of impurities (empty particles, extracellular vesicles, residual DNA, host cell proteins), and more advanced analytics and purification methods. Developers are moving toward stable producer cell lines, continuous‑processing platforms, and next‑generation purification techniques to maintain high functional titers and product quality at commercial scale.

Industry and regulatory attention is especially focused on lentiviral vectors (LVV) and adeno‑associated virus (AAV) vectors for in vivo use. LVVs are advancing for in vivo CAR‑T generation and other systemic applications, enabled by improved tropism, targeting, and safety features, while AAV remains the dominant in vivo platform for direct tissue‑targeted gene delivery.

Overall, the transition from ex vivo to in vivo is reshaping viral vector manufacturing to prioritize scalability, purity, and robust analytics, positioning these technologies as the backbone of next‑generation gene and cell therapies.