Fig. 3.

Pathways to treatment of genetic diseases. Potential pathways whereby the ability of XIST to silence trisomy can advance translational research and therapeutic strategies for systems impacted in Down syndrome. The middle pathway utilizes inducible “trisomy silencing” as a powerful experimental approach to investigate the underlying biology of human trisomy 21, information key to design of traditional pharmacotherapeutics, or potentially gene therapies. A more formidable but potentially transformative path is the possibility that an XIST transgene itself could be developed as an agent for “chromosome therapy”, which could potentially involve ex vivo or in vivo delivery. Because this approach addresses the root cause of various cell pathologies, over-expression of chromosome 21 genes, it circumvents the need to unravel and address the complexity of pathways and genes involved. While chromosome therapy is a compelling concept, and recent findings are encouraging, this nonetheless is a far-reaching and challenging prospect