Fig. 1.

Potential mechanism of AAV trans-neuronal transduction. (A) Low titer of AAV. After entering the neurons by endocytosis, AAV particles are transported towards the nucleus through the cytoskeleton, and internalized into the nucleus, where they release the single-stranded DNA genome, which is converted to double-stranded DNA. Then the target transgene is expressed to synthesize its encoded protein. (B) High titer of AAV. Most of the AAV particles entering the cell follow the process described in A (solid lines). But the overloaded AAV capsids cannot all be uncoated and express the target gene in the initially-infected neurons. Thus, the uncoated virus is transported anterogradely along the axons to the terminal and released from the synapse, then re-enter the adjacent postsynaptic neurons, and expresses the target transgene at lower incidence (dashed lines).