Behavioral and Brain Sciences

Authors' Responses

Local and global gene therapy in the central nervous system

Leslie L. Muldoona1 and Edward A. Neuwelta2a3

a1 Department of Cell Biology and Anatomy;

a2 Department of Neurology, Division of Neurosurgery

a3 Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, OR 97201.


For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient nature of transgene expression in vivo must be overcome before their use in human gene therapy becomes clinically applicable.