Accession Number : ADA290501

Title :   Toxin-Mediated Transfer and Expression of Genes in Nerve Cells.

Descriptive Note : Final rept. 3 Jan 91-30 May 94,

Corporate Author : UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD F EDWARD HEBERT SC HOOL OF MEDICINE

Personal Author(s) : Mueller, Gregory P.

PDF Url : ADA290501

Report Date : 12 OCT 1994

Pagination or Media Count : 17

Abstract : Receptor-Mediated Gene Transfer In the CNS: A Feasibility Study. This research sought to determine the feasibility of using receptor-mediated gene transfer as a mechanism for introducing the expression of foreign genes in nerve cells. DNA carrier systems were constructed using neuronal ligands that are rapidly internalized by receptor-mediated endocytosis. These proteins, principally wheat germ agglutinin and tetanus toxin C-fragment, were complexed with high expression reporter genes and applied to nerve cells in vitro, and administered in vivo into rats. Uptake and expression of the reporter genes were analyzed by standard enzymatic and histochemical procedures. While we have demonstrated, for the first time, that cells in brain can internalize and express plasmid DNA, there is no evidence that this process can be made specific through the introduction of a receptor-mediated mechanism. The findings indicate that; (1) receptor-mediated uptake and expression does occur in the CNS, and (2) lysosomal degradation is probably not the underlying basis for our inability to observe expression. From this it may be concluded that receptor-mediated uptake is not an efficient means for directing the expression of foreign genes in nerve cells in vivo.

Descriptors :   *NERVE CELLS, *GENES, FOREIGN, DEGRADATION, BRAIN, RATS, ENZYMES, PROTEINS, DEOXYRIBONUCLEIC ACIDS, CHROMOSOMES, IN VITRO ANALYSIS, FEASIBILITY STUDIES, LIGANDS, IN VIVO ANALYSIS, PATHOPHYSIOLOGY, CELLS(BIOLOGY), CENTRAL NERVOUS SYSTEM, TOXINS AND ANTITOXINS, HISTOCHEMISTRY, TETANUS.

Subject Categories : Anatomy and Physiology
      Genetic Engineering and Molecular Biology

Distribution Statement : APPROVED FOR PUBLIC RELEASE