RNA INTERFERENCE IN HUMAN ES CELLS AND THE PROSPECTS FOR FUTURE THERAPIES

ABSTRACT: Decades of genetics research have revealed a wealth of information about the molecules that make life. RNA interference has emerged as a fundamentally important biological phenomenon and as a versatile, powerful tool for biomedical research. In organisms from fungi and flies to plants and mammals, RNAi plays a multifaceted role in molecular biology by silencing genes through chromatin remodeling, interfering with protein synthesis, and--in its best-studied mode of action--quashing gene expression by cleaving messenger RNA. The discovery of RNA interference and the derivation of human embryonic stem (ES) cells have yielded exciting new possibilities for researchers and clinicians alike. While fundamentally different, aspects from these two fields may be combined to yield extraordinary scientific and medical benefits. Other proposed clinical uses center on antiviral therapies, including the inhibition of viral gene expression in cancerous cells, the silencing of hepatitis A and hepatitis B genes, silencing of influenza gene expression, and inhibition of measles viral replication. Potential treatments for neurodegenerative diseases have also been proposed, with particular attention being paid to the polyglutamine diseases such as Huntington's disease. RNA interference is also often seen as a promising way to treat cancer by silencing genes differentially upregulated in tumor cells or genes involved in cell division. A key area of research in the use of RNAi for clinical applications is the development of a safe delivery method, which to date has involved mainly viral vector systems similar to those suggested for gene therapy. Although the fields of RNAi and ES cell research are in their infancy, it is already possible to envision cell and gene therapies combining both of these strategies. Studies of ES cells differentiation may overcome concerns about the limiting number and purity of cells available for cell-replacement therapies. For this reason it is important to understand the mechanisms that regulate ES cell differentiation. This review tries to summaries the most recent developments in the field of applied combining RNAi and ES cell manipulation for basic research and future therapies, as well as current limitations and obstacles that need to be overcome, in first step. Secondly, common designs of therapy are discussed along with practical examples of such devices.
Asian Reproductive Biotechnology Society


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