Biomedical Engineering Reference
In-Depth Information
a
b
c
aptamer
A
B
A
A
B
B
d
e
A
A
B
B
ssDNA
Fig. 7.9
Logic gate for drug delivery. A stable duplex DNA (
a
) can be separated by interaction
with an aptamer (
b
) or strand displacement (
d
). The final results of the two processes are the
molecules represented in (
c
)and(
e
), respectively
the product/output strands. These can be eventually read by output-induced catalysis
of a colored product. Based on these principles, logic gates such as OR, XOR, and
AND were implemented (
Shlyahovsky et al. 2009
). In experiments, the results of
these complex logic gates can be reproduced with up to 15% errors. However, these
experiments suggest that the DNA-translator-based device could activate the release
of nucleic acids or inhibitors of harmful enzymes. In fact, this DNA-scaffold-based
device was used for the controlled release of thrombin-binding aptamers, which
inhibit thrombin. Thrombin is an enzyme that participates in blood clotting and
could cause inflammatory brain illness. Experiments showed that the hydrolytic
activity of thrombin was inhibited by 40%.
An in vitro demonstration of an autonomous biomolecular computer that anal-
yses the levels of messenger RNA and releases in response a molecule that affects
the gene expression is presented in
Benenson et al.
(
2004
). The computer consists
of an input module, which regulates the transition probabilities in the automaton
through mRNA levels, a computation module, and an output module, which
release a short ssDNA molecule depending on the input. The automaton has two
possible outcomes: YES or NO (positive or negative diagnosis) depending on the
concentration of certain molecule [four in
Benenson et al.
(
2004
)], which indicate a
specific illness. It is a stochastic automaton, with competing transitions associated
to each output, able to release a drug or its suppressor molecule in the YES or NOT
state, respectively. The sensitivity of the automaton to diagnosis can be tuned by
adjusting the concentrations of competing transitions so that the disease-indicative
mRNA can be detected at concentrations as low as 100 nM.
An encouraging sign toward a reliable in vivo molecular computing is the ability
to control mRNA with appropriate combinations of transcription factor, which
regulate synthetic genes coding (
Leisner et al. 2010
). This computer consists of
sensory, computational, and actuation modules, which have yet to be optimized.
Not only computations involving individual DNA strands have been demon-
strated, but also collective computations in living cells. For example, a genetic
circuit able to generate synchronized oscillations (genetic clocks) in a thriving
Search WWH ::
Custom Search