Biologically speaking, T cells will only thrive in the presence of certain chemicals called cytokines that are normally delivered or triggered by other cells that are part of a proper immune response. In its work, the team implanted genes in the T cells, enabling the cells to produce the cytokines for themselves. This ability, however, is controlled by another addition: a series of switches, encoded in RNA, that allow cytokine production to proceed only in the presence of a drug.
With the help of co-author Michael Jensen, MD, cancer immunology researcher at the City of Hope's Beckman Research Institute in Duarte, Calif., the team tested a variety of modifications both in mice and in cultures of human T cells. They used different drugs to trigger the production of different cytokines. Generally, the results showed that their engineering produced healthier, faster-growing populations of the T cells, until the drugs were withdrawn and growth shut down. In the human cell cultures, for example, the technology led to a 24 percent increase in the live T-cell population compared to controls and 50 percent fewer cells dying off.
The research can be traced back to 2007 at Caltech, when Smolke led the development of the ribozyme-based RNA switches. At the time the switches were synthesized as fundamental, generally useful components. Now they have found an advanced use. By analogy, they are light switches that have now been successfully integrated into a working circuit.
"Originally we were looking at how can you design an RNA molecule that can detect a chemical and then translate that into a gene-regula
|Contact: David Orenstein|
Stanford University Medical Center