Gene therapy vectors have to survive an obstacle course — circulation, immune surveillance, tissue barriers — before ever reaching and successfully transducing their target cells with the therapeutic gene.
transduction_prob ~ dose * tropism * proximity_to_target
cleared vectors removed at immuneRate
- Delivery path irregularity — how much the vector's path deviates as it navigates capillary beds and tissue barriers.
- Circulation speed — how fast the vector moves through the vascular system toward its target organ.
- Vector dose / tropism — how much vector is dosed and how selectively its capsid targets the intended cell type.
- Immune clearance — how quickly the patient's immune system neutralizes circulating vector particles before they reach target cells.
Vector immunogenicity is a major real-world bottleneck: pre-existing antibodies against common AAV serotypes are why some gene therapy trials pre-screen patients and exclude those already immune to the chosen vector.