DNA-based computing just got a big boost. A method of amplifying weak chemical signals in a way that can be tailored to specific molecules has brought DNA-based circuits closer to practical applications.
In conventional digital electronics, electrons are the carriers of information. In DNA-based circuits, fragments of single-stranded DNA are the carriers of information instead. Rather than encoding 1s and 0s as high and low voltages, DNA-based circuits use high and low concentrations of given fragments of DNA.
Last year, Georg Seelig, and colleagues in in Pasadena, California, US, developed the building blocks for a DNA-based circuit.
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They created logic components 鈥� AND, NOT and OR gates 鈥� using strands of DNA. An AND gate, for instance, is a molecule that releases an 鈥渙utput鈥� strand of DNA only when two 鈥渋nput鈥� strands were present in the solution.
Programmable reaction
These logic gates could be combined or cascaded to build simple circuits ().
鈥淏ut they didn鈥檛 have any amplification in them,鈥� says Winfree. 鈥淪o the number of molecules in was the same as number of molecules out.鈥�
Amplification is essential if DNA-based computing is to have practical applications. If, say, a circuit has to detect the presence of a tiny amount of DNA in its environment, the DNA would have to be 鈥渁mplified鈥� before the circuits could work.
Polymerase chain reaction (PCR), a well-known process in biochemistry, can take a miniscule amount of DNA and amplify it exponentially, but the process relies on enzymes.
Now David Zhang in Winfree鈥檚 group and colleagues have shown how to perform DNA amplification without the use of enzymes, making the process simpler and much more configurable, since it can be tailored to any DNA strand.
Exposed fragment
The process makes use of the fact that complimentary stretches of DNA will bind together. A 鈥渃atalyst鈥� strand of DNA is used to pull another strand free from several strands bound together.
The catalyst strand does so by attaching to a fragment left exposed at one end, called the 鈥渢oehold鈥�. It eventually attaches itself completely, 鈥渦nzipping鈥� the other strand. Once the target strand has been freed, another strand is used to detach the catalyst through a similar process so that it can be reused.
The end result of this is that a small amount of catalyst material released a large amount of the output molecule. The team showed that the concentration of the output molecule could be up to 900 times the concentration of the catalyst.
Driving force
The reaction is also programmable, in the sense that one can choose the exact sequences of the various molecules to fit the design of a particular DNA-based digital circuit.
The reason why this reaction proceeds at all has to do with entropy. 鈥淛ust the fact that there are more places the molecules can be provides a driving force that is actually quite strong, and makes the reaction want to go forward,鈥� says Winfree. 鈥淵ou want to generate entropy, nature loves chaos.鈥�
While the process is not yet competitive with PCR, 鈥淚t sets some of the principles for how to design such systems from scratch without using enzymes,鈥� says Winfree.
Roy Bar-Ziv of the Weizmann Institute of Science in Rehovot, Israel, writes in the journal Science (vol 318, p 1078) that the approach could be embedded in biochemical logic circuits and 鈥渦sed to amplify weak signals and thus increase the speed and performance of the circuit鈥�. Such catalytic circuits could be used to 鈥渃ontrol nanoscale devices,鈥� he adds.
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