Antibodies for targeted gene therapy: extracellular gene targeting and intracellular expression

Antibody genes of human origin and human antibodies directed against human proteins have become widely available in recent years. These are valuable reagents for gene therapy applications, in which the use of human proteins and genes allows for increased therapeutic benefit. Engineered human antibodies can be used in gene therapy both as a component of a gene delivery system and as a therapeutic gene. As the targeting moiety of a gene delivery system, the antibody should meet certain criteria that have been previously determined from other clinical applications 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 of human antibodies in this application should therefore be superior to approaches which use rodent-derived antibodies. Another application of 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 sites for any known molecule is well documented. The ability to harness this information and use these highly specific binding molecules as medicines 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.