Researchers at the Duke University have developed an analog DNA computer which can perform basic mathematic functions. The potential for medical applications could be huge.

This is accomplished by forming and breaking bonds between different strands of the synthetic DNA in a test tube.

 

DNA Computers

DNA-based computation uses the properties of molecules to perform simple mathematical operations. In this way, it is possible to have tiny nanoscale biocompatible computers able to make the most basic decisions. Scientists hope that one day they could connect a large number of such molecular modules, which play the same role as the conventional logic gates in electronics, to perform more complex computations. Unlike an electronic circuit which uses voltages and currents as a representative of inputs and outputs, the DNA computation utilizes the concentration of different strands of DNA as signals.

 

Duke’s Analog DNA Computer

The first logic gate with synthetic molecules is related to early 1990s. Since then there have been reports of designing DNA computers to perform functions such as calculating square roots and playing tic-tac-toe. However, these researchers have mainly considered DNA as a digital device in their circuits. This is mainly due to the fact that DNA itself already has a digital approach to arranging base pairs and encoding data—similar to the way a computer uses binary codes to store data.

In contrast, the new circuit, which was made by John Reif’s team of Duke University, can directly measure the concentration of DNA molecules in an analog fashion without the need for devices which convert these concentrations into digital. Scientists believe that the analog approach reduces the number of the required strands of DNA. Moreover, many signals such as vital signs and physiological measurements necessary for diagnosis cannot be represented simply by two on and off states. Hence an analog approach will be much more attractive.

 

The DNA computer is based on the ability of DNA strands to zip and unzip with each other—depending on how similar the base pairs are in the two strands. This is similar to Velcro or magnets with complementary hooks or poles. Each strand of DNA can pair up with another suitable strand of DNA. The newly-attached strand may displace and detach a previously bound one in a predictable way. The released strand itself may find its corresponding DNA strand and bind itself to that. This leads to a domino effect which can be designed to give a final desired result.

In other words, by considering the sequence in which all these bonds form and break, scientists can design a DNA computer to perform a particular operation.

As mentioned above, a DNA computer uses concentration of different strands of DNA as signals and the variation of the concentration of these strands of DNA during the computation will be according to the designed operation.

 

Professor Reif (Right) and Graduate Student Tianqi Song (Left) in the lab. Image courtesy of Duke University.

 

Reif’s team suggests that by applying Taylor Series and Newton Iteration methods, it is possible to build DNA structures which approximate functions much more complicated than polynomials. Utilizing these techniques, we can extend the analog DNA circuit to calculate functions such as logarithms and exponentials.

 

Potential Applications

DNA computers are very slow, and the calculations can take hours before reaching a valid result. Therefore, we do not expect a DNA-based structure to compete with a modern silicon-based computer. However, these circuits are far tinier than conventional solutions and are capable of operating in wet environments such as inside the bloodstream.

As a result, these structures can prove to be extremely advantageous in building smart therapeutic agents. Such smart products can be programmed to monitor different chemicals of the blood and, with no human intervention, can respond appropriately by releasing a specific DNA or RNA which has a drug-like effect.

As an example, a biocompatible drug can monitor the glucose levels in the blood and release insulin when necessary.

In diseases such as leukemia, a DNA-based gate can discriminate between healthy and unhealthy cells by sensing the different characteristics of the cells. Today’s treatments for leukemia normally make an indiscriminate attack to both the healthy and unhealthy cells. This weakens the patient’s immune system and can even lead to their death.

Reif’s group is, in particular, designing DNA-based devices which can detect certain types of cancer and force the immune system to fight back against the disease.

 

The researchers describe their approach in a paper in the August issue of the journal ACS Synthetic Biology.

 

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