Symbiosis therapy: The potential of using human protozoa for molecular therapy

Abstract

The concept of symbiosis is proposed as a disease therapy model. It is hypothesized that protozoa that live naturally in human tissues can be genetically modified for the production and delivery of therapeutic proteins. Approximately 30 identified species of protozoa live in a variety of human tissues, both intracellularly and extracellularly. Leishmania, one species of human protozoa, has been genetically altered for conditional auxotrophy and has shown no pathology in both mouse and nonhuman primate safety tests. Several species of protozoa have been transfected with a variety of genes and have successfully manufactured active foreign proteins. Protozoa have biochemical mechanisms to glycosylate proteins. Human protozoa have evolved sophisticated mechanisms for evading immune rejection and can sometimes persist for the lifetime of the host. Symbiosis therapy does not involve genetic alteration of the host and is potentially fully reversible. Research on treating genetic diseases is currently ongoing. For example, there is a group of more than 40 genetic diseases, lysosomal storage diseases, which result from defects in lysosomal enzymes primarily in macrophages. Leishmania specifically targets the lysosomal compartment of the macrophage and therefore may be the optimal vector for treatment of many of these diseases.