Figure 2: (a) the Petri dish used in the BD2-Red/BD3 experiment (from Basu [ 1]) is shown with the sender disk in the middle. (b) A bullseye pattern is captured with a fluorescence microscope after incubation overnight with senders in the middle of an initially undifferentiated ‘lawn’ of BD2-Red and BD3 cells. The senders in the middle are expressing CFP. (c) Another bullseye pattern is shown, this time with a mixture of BD1 and BD2-Red cells; scale bar, 5mm.

Reprinted by permission from Macmillan Publishers Ltd: Nature [ 1], copyright 2005.

mous molecular systems consisting of sensors, computers, and actuators, which are smaller than cells, and can even be put inside a cell.

DNA molecules are versatile because they can be used for all three kinds of components, and the field of DNA nanotechnology (sometimes referred to as DNA robotics or DNA nano-robotics) has developed over the last few decades [ 5]. For example, if such a molecular system is implemented inside a cell, various molecules inside a cell, including mRNA molecules copied from a gene on a chromosome, can be used as input to the system.

Just three kinds of reactions among DNA or RNA molecules—hybridization, denaturation, and branch migration— are often sufficient to construct interesting molecular systems. DNA or RNA molecules form double strands with hydrogen bonds between complementary bases, i.e., A-T (or A-U) and G-C. Hybridization is the reaction in which complementary segments of DNA or RNA bases form a double strand. Denaturation, or “melting,” is the reverse of hybridization, in which a double strand comes apart. Branch migration is the reaction in which a branching point formed by three single strands of DNA or RNA moves as shown in Figure 3. This is also called “strand displacement,” because a double strand may eventually exchange one of its complementary segments.

Seelig and his colleagues successfully developed an AND gate using

“Synthetic biology
researchers are
trying to construct
artificial systems
by remodeling
existing cells. The
difference between
genetic engineering
and synthetic
biology may not
be immediately
obvious. Genetic
engineering
essentially tries to
add a single function
by inserting a gene
into a cell. Synthetic
biology, on the other
hand, tries to add a
system to a cell.”

the branch migration reaction [ 7]. This AND gate is a structure consisting of three DNA strands with single strands of DNA or RNA as its input and output. As shown in Figure 4, if only two input strands exist in the system, an output strand is released by the two-step branch migration. In a similar manner, they developed other logic gates, including an OR gate and a NOT gate. Note that we can use an output of one gate as the input to another, because both input and output are single-stranded DNA or RNA molecules. These gates are thus sufficient to simulate any logical formula. They are sometimes called “enzyme-free logic gates,” because they do not require enzymes for processing DNA or RNA molecules.

DNA logic gates can also be used for a drug delivery system. Suppose that the input are specific mRNA molecules from cancer cells and output are those that can suppress the expression of the cancer genes by the so-called antisense strategy or RNA interference.

We can accept other kinds of molecules as input to a system, using DNA molecules called “aptamers,” which have special sequences that bind to specific molecules. For example, an adenosine triphosphate (ATP) aptamer can combine with ATP to form a complex structure. Thus, DNA/RNA can be used as a biosensor for various chemical substances. Physical signals such as light can also be sensed by DNA