ANTIBODIES FOR TARGETED GENE-THERAPY - EXTRACELLULAR GENE TARGETING AND INTRACELLULAR EXPRESSION

Antibody genes of human origin and human antibodies directed against h uman proteins have become widely available in recent years. These are valuable reagents for gene therapy applications, in which the use of h uman proteins and genes allows for increased therapeutic benefit. Engi neered human antibodies can be used in gene therapy both as a componen t of a gene delivery system and as a therapeutic gene. As the targetin g moiety of a gene delivery system, the antibody should meet certain c riteria that have been previously determined from other clinical appli cations of antibodies. These include bioavailability, specificity for the target cell, and rapid clearance. In addition, if repeat delivery of therapeutic genes is going to be needed, then gene delivery vectors should be non-immunogenic to allow repeated administration. The use o f human antibodies in this application should therefore be superior to approaches which use rodent-derived antibodies. Another application o f antibodies in gene therapy is the use of antibodies expressed inside the cell (intrabodies) as therapeutic agents. The power of the immune system to rearrange a limited set of genes to create recognition site s for any known molecule is well documented. The ability to harness th is information and use these highly specific binding molecules as medi cines to inhibit an unwanted cellular function is a promising advance in the field of molecular medicine, and in particular, in the field of intracellular immunization. (C) 1998 Elsevier Science B.V.