( A new platform for regulating the expre...)New Platform for Regulating Expression of Therapeutic Genes Unveiled,Health

A new platform for regulating the expression of therapeutic genes, which will have major implications for gene and cell therapy, was presented today at the 10th Annual Meeting of the American Society of Gene Therapy (ASGT) in Seattle.

Carefully regulating gene expression is crucial to the success of gene and cell therapy. For many applications, gene transfer is being employed to engineer cells for therapeutic factor production, expansion, selection of a desired cell type and even fail-safe suicide. These applications often require precise regulation in order to ensure gene expression in the correct tissue and prevent it in unwanted cell types.

Now, a team of scientists led by Dr. Luigi Naldini at the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) in Milan have developed a new platform. Dr. Naldini and colleagues provided a striking demonstration that their new design can enable delivered genes to become highly responsive to a cells identity. This is particularly relevant for the emerging field of stem cell gene therapy, in which genes are delivered into a cell that can give rise to many distinct cell types.

To achieve their goal, the TIGET scientists came up with a strategy to take advantage of a recently discovered network of gene regulation mediated by small RNA molecules, known as microRNA.

MicroRNAs downregulate the expression of specific genes in cells where the gene is not needed, and thereby have an important influence over the identity of the cell. More than 350 mammalian microRNAs have been identified, with many being present only in some specific tissues and cell types.

Dr. Naldinis group showed that the addition of microRNA binding sites into their gene delivery vectors results in gene regulation dictated by the cells own cognate microRNA. Simply put, they could engineer their gene to be turned off in cells where the microRNA is present. As a proof-of-principle, the resea
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