There is strong interest in developing practical strategies for gene delivery to the central nervous system (CNS). Direct delivery into the brain or spinal cord is highly invasive as well as inefficient or hazardous using most current vector systems. Our objective was to generate innocuous gene vehicles that would be effectively taken up by axons and then home to the neuron cell bodies. Vectors derived from Adeno-Associated Virus (AAV), a harmless human parvovirus, offer strong starting candidates for deriving such vehicles. Enhancing the axonal uptake of AAV, and conferring more efficient retrograde transport capabilities upon the virus, should produce near ideal gene transfer vehicles for the CNS. To enhance retrograde transport of the virus, peptides mimicking binding domains for cytoplasmic dynein were inserted in the capsid by directed mutagenesis. In separate clones, peptides derived from an NMDA receptor antagonist were also introduced to provide a specific affinity for this receptor. When combined, these two functionally distinct classes of mutation enabled efficient gene transfer into neurons under conditions not permissive for standard AAV-2 vectors prepared under the same conditions. These results hold strong promise for the development of safe, convenient vehicles to target genes and other sequences to neurons, enabling new and novel approaches for the treatment of multiple neurological disorders.