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New Platform for Regulating Expression of Therapeutic Genes Unveiled

rchers used a lentiviral vector to introduce a gene encoding a fluorescent protein into human embryonic stem cells. Their gene contained target sites for a microRNA specific of neuronal cells. While undifferentiated, the embryonic stem cells expressed high levels of the fluorescent gene, however, as soon as the cells turned into neurons, the engineered gene was turned off in response to the presence of the microRNA in the neurons. So versatile is their approach, that they could even demonstrate the reverse. By changing the microRNA binding site in their vector to one recognized by an embryonic stem cell-specific microRNA, their vector was kept off in immature embryonic stem cells, but began to express itself as the cell turned into more defined tissues. This new platform now provides a means for scientists to achieve highly tailored gene expression patterns when delivering recombinant genetic material into cells.

We had been looking for ways to regulate transgenes better, when it hit us, nature had already solved the problem for us, says Dr. Brian Brown, one of the studies authors. Now, we can utilize a cells own regulatory network to control a gene we introduce.

Dr. Naldinis 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.

The American Society of Gene Therapy is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of gene and related cell and nucleic acid therapies and the promotion of professional and public education in the field.


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