The genetic device holds promise for developing cancer-specific gene therapies and could create new consulting opportunities for pathologists and clinical laboratory scientists
In Israel, researchers are making progress on the futuristic concept of biologic, medically-savvy computers that are so small they can fit inside human cells and roam the body detecting and treating diseases in vivo. This is another example of how new technologies can shift diagnostic testing away from clinical laboratories.
This groundbreaking work is being done at the Weizmann Institute of Science in Rehovot. The research team has designed a genetic device that is inserted into bacteria cells where it operates independently. This device is programmed to identify certain disease parameters and mount an appropriate response, according to a story published by Science Daily.
Device Diagnoses the State of Cells and Produces a Therapeutic Response
This synthetic, programmable device is made up of a DNA sequence. It diagnoses the state of a cell based on predefined markers and produces a corresponding therapeutic output. The investigators, Professor Ehud Shapiro, Ph.D., and Tom Ran, Ph.D., of the Biological Chemistry and Computer Science, and Applied Mathematics Departments, also noted that this device may well be a basis for developing programmable drugs.
Their study was published in the September 7, 2012, issue of Nature’s Scientific Reports. They first created a device that functioned like what is known in computing as a NOR logical gate. The device was programmed to check for the presence of two transcription factors (TFs).
Transcription factors are proteins that control gene expression in cells. When the device is inserted into a bacterium, it searches for TFs and performs a “roll call” of TFs. If results match the preprogrammed parameters, the device responds by creating a protein that emits a visible green light, indicating a “positive” diagnosis, explained a Weizmann Institute press release.
Professor Ehud Shapiro, Ph.D. (left), and colleague Tom Ran, Ph.D. (right), are scientists at Israel’s Weizmann Institute of Science. Their research team has developed a biological computer that can be inserted into bacterium to detect malfunction in the cell—such as what happens with cancer—and mount an attack that causes the cell to self-destruct. (Photos copyright Weizmann Institute of Science.)
To test the device’s accuracy, the device was programmed to check for two types of TFs. The research team inserted the device into four types of genetically engineered bacteria, as follows:
1) Bacteria making both types of TFs;
2) Bacteria making no TFs; and,
3) Two types of bacteria that each make one type of the TFs.
Following the insertion of “biologic computers” into the bacteria, only the appropriate bacteria shone green.
Pictured above is the NOR Logic Gate designed by the research team at Israel’s Weizmann Institute of Science. It was programmed to look for two transcription factors inside a cell. If both transcription factors are missing, a green light is emitted. (Diagram copyright Weizmann Institute of Science.)
Researchers at the Weizmann Institute plan to replace the light-emitting protein with one that can affect the cell’s fate, such as a protein that causes it to commit suicide. Therefore, only cells with “positive” diagnoses will self-destruct, they noted. With success of this study, the researchers will next test ways to recruit as an effective system that can conveniently be inserted into the human body for medical purposes.
Study Holds Promise for a Genetically Engineered Cure for Cancer
Another goal is to create similar “biological computers” using human cells, which are more complex than bacteria. “The system presented in this work demonstrates how the NOR gate can analyze TF inputs based on their digital presence or absence,” wrote the researchers in the Nature Scientific Reports article.
The researchers further noted that digital TF markers enable the greatest specificity and optimization of the target, which holds promise for developing gene therapies for specific cancers. “A mammalian system based on this design may allow analyzing the presence or absence of numerous cancer-related TFs and the induction of cell death if all TFs were aberrantly expressed, and therefore may have important future biological and medical applications,” they explained.
Should these biological computers prove feasible, this would open up a whole new area of clinical practice for pathologists and clinical laboratory scientists. There would be a need for patient’s state of health to be assessed and the right mix of biological computers administered to the patient.
—By Patricia Kirk
Related Information:
A Genetic Device Performs DNA Diagnosis
A programmable NOR-based device for transcription profile analysis
Device Made of DNA Inserted Into Bacterial Cell Works Like a Diagnostic Computer
A genetic device performs DNA diagnosis
A library of programmable DNAzymes that operate in a cellular environment
