Synthesizing artificial devices that redirect cellular information at will

Cells respond to signals from their surrounding environment. External signals activate a sequence of events inside the cell that can change how it behaves. These events are often called signaling pathways and they typically change the cell’s behavior by changing the activity of its genes. A major objective of the field of genetic engineering is to customize or artificially create new signaling pathways to make cells behave in certain ways. The ability to control a cell’s behavior is likely to have a major impact on human health and medicine. For instance, it may be possible to reprogram signaling events in cancer cells so that they die rather than grow rapidly. Researchers are developing artificial genetic devices to manipulate signaling pathways. Molecules of ribonucleic acid (or RNA) are widely used to design such devices. In nature, RNA molecules are highly versatile: messenger RNA molecules carry genetic information in a form that can be translated into protein, while other RNA molecules fine-tune gene expression and perform a host of other roles. RNA is apt for artificial devices because it can be tailored to detect signals and convert this information into a predictable outcome, such as turning specific genes on or off. In 2016, researchers constructed an RNA device to control the expression of genes in response to particular signals. However, this device was too large to deliver efficiently inside cells. Now, Liu, Li, Chen et al. – including some of the researchers involved the 2016 study – design smaller RNA devices to overcome this limitation. Each new device consists of two RNA components: one that recognizes the signal, and another that recognizes the messenger RNA of a target gene. Together the two components trigger the desired change in gene expression in response to a specific signal. The devices were shown to have multiple uses such as making new connections in a signaling pathway and creating new signaling networks. Furthermore, Liu, Li, Chen et al. engineered one device such that it was able to specifically turn off genes in a particular signaling pathway that allows human bladder cancer cells to divide. By silencing these genes, the cancer cells were less able to grow. These newly developed RNA devices should allow other researchers to customize cellular information and may have future therapeutic applications as well.