For many applications, gene transfer is being employed to engineer cells for therapeutic applications, chek the following links for article 1 IFR, 2 (Nature), 3 (NIH), that 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 Naldin i at the San Raffaele Telethon Institute for Gene Therapy ( HSR-TIGET ) in Milan have developed a new design that enable delivered genes to become highly responsive to a cell’s identity with the helps of gene regulation mediated by small RNA molecules, known as microRNA. 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.
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.
Addition of microRNA binding sites into their gene delivery vectors results in gene regulation dictated by the cell’s own microRNA. Simply put, they could engineer their gene to be turned off in cells where the microRNA is present.
Dr. Naldini’s group has already begun to successfully exploit microRNA regulation for achieving stable long-term correction of hemophilia in the mouse model and for improving the safety of hematopoietic stem cell gene therapy.