[16,63], for example, for logic control of gene expression [64]. RNA‐based computing systems are particularly promising for in vivo operation, thus being excellent candidates for nanomedicine with implemented Boolean logic [65]. DNA computers can operate as a Turing machine [51] and can be sophisticated enough to mimic neural network computations similar to human brain, obviously in a very simplified way [66]. The DNA computing systems playing a tic‐tac‐toe game against human have been “smart” enough to win [13,67–69] (Figure 1.7).
Figure 1.6 The principle of Leonard Adleman's DNA computer to solve the “traveling salesman problem” (see detailed explanation in Ref. [54]).
Source: Based on Parker [54].
Figure 1.7 The DNA computer playing the tic‐tac‐toe game. Shown in the foreground is a cell culture plate containing pieces of DNA that code for possible “moves.” A display screen (background) shows that the computer (red squares) has won the game against a human opponent (blue).
Source: Courtesy of Prof. Milan Stojanovic, Columbia University.
The progress in the DNA computing has been based on three major developments: (i) the use of sophisticated DNA structures (e.g., origami), (ii) the use of more powerful instrumentation for automatic operation of DNA computing steps (DNA chips), and (iii) specialized programming languages specifically developed for the DNA computing. The invention of the DNA origami structures [70,71] – nanoscale folding of DNA resulting in nonarbitrary two‐ and three‐dimensional shapes [72,73] (Figure 1.8) – resulted in further sophistication of the DNA computing systems [74], capable of operating as nanorobots in living organisms [75–77]. The use of DNA microarrays (DNA chips [78]) allowed simultaneous analysis of large numbers of DNA probes [53], thus introducing a powerful hardware for the DNA computing (Figure 1.9). A special computational language, DNA strand displacement (DSD) tool, similar to programming languages used in electronic computers, has been developed by scientists at Microsoft Research for programing DNA computing [79,80] (Figure 1.10). The language uses DSD as the main computational mechanism, which allows devices to be designed solely in terms of nucleic acids. DSD is a first step toward the development of design and analysis tools for DSD and complements the emergence of novel implementation strategies for DNA computing. The DNA computation can be performed in living cells by DNA‐encoded circuits that process sensory information and control biological functions. A special computing language, “Cello,” has been developed for programing DNA logic operations in vivo [81]. Overall, the use of computing languages simplified the design of DNA computing systems of high complexity.
Figure 1.8 Atomic force microscopy (AFM) images of DNA origami with different shapes.
Source: From Hong et al. [73]. Reprinted with the permission of American Chemical Society.
Figure 1.9 An example of a DNA chip used in the DNA sensing and computing. The chip represents a DNA microarray as a collection of microscopic DNA spots attached to a solid surface. Each DNA spot contains picomoles of a specific DNA sequence. The chip allows simultaneous analysis of many DNA probes. The analysis of the probes can be performed optically (as it is in the present example) or electrochemically (then the chip should be based on a microelectrode array).
Source: Courtesy of Argonne National Laboratory and Mr. Calvin Chimes.
Figure 1.10 Logic program (a) and automatically generated chemical reaction network (b) for a DNA strand displacement example.
Source: Adapted from Spaccasassi et al. 2019 [80] with permission; open access paper.
1.3 DNA‐Based Information Storage Systems
Human civilization generates hugeamount of information increasing exponentially and required to be stored. The total digital information today amounts to 3.52 × 1022 bits globally and at its consistent exponential rate of growth is expected to reach 3 × 1024 bits by 2040 [82]. Data storage density of silicon chips is limited, and magnetic tapes used to maintain large‐scale permanent archives begin to deteriorate within 20 years. Alternative methods/materials for storing high density/large amount of information with reliable preservation over long period of time are urgently needed. DNA has been recognized as a promising natural medium for information storage [83]. Indeed, the DNA molecules were created by nature to keep the genetic code, which can be easily “written” and “read” by biomolecular systems. With information retention times that range from thousands to millions of years, volumetric density 103 times greater than flash memory, and energy of operation 108 times less, DNA is a memory storage material viable and compelling alternative to electronic memory. Recent research in the area of information storage with DNA molecules resulted in the proof‐of‐the‐concept systems [82,84–87], while the practical use of the DNA memory systems is only limited by technological problems. Both processes in the information storage with DNA, “writing” and “reading” information, are available, but they are not as simple as needed to be implemented with the present computer technology. In other words, the DNA memory is technically possible, but it is not convenient enough to be integrated with standard Si‐based computers operated by end users.
Synthetic procedure for production of DNA molecules with specific nucleotide sequences is well known in organic chemistry [88] and can be used to “write” information in the DNA. Once the DNA molecules with the encoded information are prepared, they can be multiplied using a polymerase chain reaction (PCR) [89–92] (Figure 1.11), which is a technique to make many copies of a specific DNA in vitro (in a test tube rather than an organism). This technique is rather advanced in the instrumental realization but still requires special apparatus that cannot be connected easily to an electronic computer, at least at the end‐user convenience. “Reading” the DNA‐encoded information (DNA sequencing [93]) was advanced during the Human Genome Project [94] and presently is very technologically effective. Further improvements
