Chapter 16. Targeting of Poliovirus Replicons to Neurons in the Central Nervous System

Summary

In the central nervous system (CNS), poliovirus replicates primarily in motor neurons in the anterior horn of the spinal cord. To exploit the cellular targeting of poliovirus to motor neurons, we have developed an expression vector in which the capsid genes for poliovirus have been removed and substituted with foreign genes. These genomes (referred to as replicons) when introduced into cells undergo an amplification process that results in high-level expression of the foreign protein. We have developed a method to encapsidate replicons into authentic poliovirions by providing the capsid proteins in trans. The encapsidated replicons maintain the tropism of poliovirus for motor neurons in the CNS and, in contrast to poliovirus, even after multiple inoculations directly into the CNS do not result in neuron destruction. We have shown that replicons can express high levels of biologically active molecules in the CNS. The expression of foreign proteins in neurons from replicons is rapid, peaking at 24–48 hours post inoculation into the CNS; by 96 hours the expression of proteins from replicons ceases and is no longer detectable. The use of replicons as gene delivery vectors for molecules that would have therapeutic benefit in spinal cord injuries and neurological diseases is discussed.