Biology Reference
In-Depth Information
TABLE 9.2
Different Inductive Stimuli for Synthetic Gene Circuits
Inductive Stimuli for Synthetic Gene Circuit
References
Reeves et al.
104
Jiang et al.
105
Tonack et al.
106
Antibiotics
Hartenbach et al.
107
Weber et al.
108
Weber et al.
109
Food supplements
Chong et al.
110
Tascou et al.
111
Drugs and medications
Valenta et al.
112
Gitzinger et al.
113
Skin-penetrating chemicals
Kemmer et al.
114
Kemmer et al.
115
Weber et al.
116
Endogenous metabolite, hormone, or redox state
Weber et al.
118
Weber et al.
119
Gaseous chemicals, i.e. smell
Weber et al.
119
Ye et al.
120
Physical stimuli, i.e. light, electrical pulse
One of the first inductive stimuli which synthetic gene circuits were engineered to respond
to was the presence/absence of antibiotics, best exemplified by the TET
ON
and the TET
OFF
system developed for mammalian cells.
104
106
Despite this achievement, the use of
antibiotics for the induction of synthetic gene circuits has limited therapeutic application.
For example, the systemic administration of antibiotics may kill off symbiotic bacterial
populations within the patient (for example, in the gut), as well as encourage the
development of antibiotic resistance.
121
166
To allay safety concerns for therapeutic applications, it may be advantageous to design
synthetic gene circuits that are responsive to nontoxic and orally ingestible food supplements
such as vitamins, amino acids, and flavorings. Indeed, synthetic gene circuits responsive to
the amino acid arginine,
107
vitamin H (Biotin),
108
and strawberry flavor 2-phenyl ethyl
butyrate
109
have been reported. Nevertheless, it must be noted that because vitamins and
amino acids are found naturally within the human body and are implicated in key metabolic
processes, ingestion of high doses may interfere with the patient
s own metabolism.
'
For certain therapeutic applications, it may be advantageous to engineer synthetic gene
circuits to be responsive to specific drugs and medications administered to the patient. Chong
et al.
110
developed a synthetic gene network to control adenoviral vector replication based on
the response to the immunosuppressive drug rapamycin. In another study by Tascou et al.,
111
a synthetic gene circuit responsive to the antidiabetic drug rosiglitazone was constructed.
Besides oral and intravenously administered substances, synthetic gene circuits can also be
engineered to be responsive to skin-lotion-based chemicals that can penetrate the skin. This
is best exemplified by phloretin, an anti-bacterial plant defense metabolite found naturally
within apples, and commonly utilized as a penetration enhancer for skin-based drug
delivery.
112
Gitzinger et al.
113
constructed a synthetic gene circuit responsive to phloretin by
using a flavonoid-specific biosensor (TtgR) that interacts with phloretin and binds to a
specific operator sequence (O
TtgR
).
In addition to exogenous stimuli, it may be necessary in some therapeutic applications to
engineer synthetic gene circuits to respond to endogenous stimuli in situ within the human
