WESTPORT, CT (Reuters Health) Dec 21 - A vector derived from an insect baculovirus can transfect neural cells in culture and in rodents, French researchers report in the December 19th issue of the Proceedings of the National Academy of Sciences.
The nuclear polyhedrosis virus Autographa californica is potentially ideal for gene therapy of nondividing cells because it is expressed episomally and its promoter is silent in mammalian cells, according to Dr. J. Mallet from Centre National de la Recherche Scientifique, in Paris, and colleagues.
To see if a version of this baculovirus expressing green fluorescent protein could transfect neural cells, they infected two neuroblastoma cell lines, three human primary neural cultures and adult astrocytes with the virus and found efficient transduction of the virus in all but one of the neuroblastoma cell lines. Expression was improved by the addition of butyrate, which inhibits histone deacetylases, "highlighting the importance of the chromatin state of the baculovirus genome in the infected cells to express the transgene."
The researchers also infected telencephalic cultures from human embryonic brains and found efficient transduction, particularly of neuroepithelial, neuroblastic, and glial cells. At a multiplicity of infection of 25, the reporter gene was expressed in over 50% of transduced cells.
The baculovirus could also transduce neural cells after direct injection into the brains of rodents, and was not inactivated by the complement system. Within a week of injection, immunohistochemical staining showed that transduced cells were mostly astrocytes were with a few neurons.
"Baculovirus is a promising tool for gene transfer into the central nervous system both for studies of the function of foreign genes and the development of gene therapy strategies," Dr. Mallet and colleagues conclude.
Further work "could be used to design a new generation of baculovirus-derived vectors able to transduce neural cells ex vivo and in vivo with a high efficacy and to sustain a long-term expression," they add. "These vectors might then become a novel gene delivery system for the treatment of acquired or inherited diseases of the central nervous system."
Proc Natl Acad Sci USA 2000;97:14638-14643.
2000 Reuters Ltd.