Biology Reference
In-Depth Information
CONCLUSION: CHALLENGES AND SAFETY ISSUES
As synthetic biology makes major inroads into diverse therapeutic applications, an obvious
key requirement is system robustness; that is, long-term stability, tight control, and
consistent performance of the engineered synthetic gene networks. A major obstacle to
achieving this requirement is that there is a limit to the size of genetic programs that can be
transferred into human cells with clinically approved viral and plasmid vectors, which
would in turn necessitate the use of multiple vectors for piecemeal transfer of different
components of a synthetic gene network into human cells. This would obviously
compromise system stability, and make it difficult to achieve tight control of synthetic gene
circuits.
Translation of synthetic biology into clinical applications demands stringent evaluation of
toxicity and other safety issues associated with the introduction of engineered synthetic gene
networks into the human body. Of particular concern is the possibility of genetically
modified cells and organisms causing unanticipated adverse effects on patients, such as
cancer. There is also a risk of inadvertent transmission and spread of genetically modified
organisms (for example, commensal bacteria) to human populations and the environment.
Hence, a top priority for synthetic biology is
that is, the
development of safety switches or brakes within synthetic gene networks that can restrain
growth and proliferation of genetically modified cells and organisms.
biosafety engineering;
'
'
Currently, the synthetic biology field does not have too many studies that specifically
address safety issues pertaining to the construction of synthetic gene circuits and their
interaction with the human body and environment. Nevertheless, what is certainly needed
is stringent regulatory oversight exercised by international agencies and local government
bodies over research institutions and commercial entities involved in the creation of
genetically modified cells and organisms. Perhaps an international registration system with
standardized nomenclature should be set up to ensure traceability of genetically modified
cells and organisms. This may be facilitated by making it mandatory for research institutions
and commercial entities to uniquely tag the DNA sequence of all genetically modified cells
and organisms that they develop. Compulsory registration and tagging will undoubtedly
motivate research institutions and commercial entities to operate with greater accountability
and transparency. Additionally, new legislation should also make provisions for compulsory
biosafety engineering of all genetically modified cells and organisms, to inhibit their growth
and survival outside a contained environment, once the technology for doing so is matured
and widely available.
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To date, a substantial portion of the synthetic biology toolkit has been derived from
bacterial prokaryotic systems. Hence, another major safety concern is that heterologous
proteins (particularly from prokaryotic systems) expressed by synthetic gene networks might
trigger an immune response within the patient. Accordingly, there is a critical need to find
new building blocks of synthetic gene networks from human systems. An expanded
synthetic biology toolkit based on human genes, proteins, and RNA is unquestionably
crucial for translation into clinical practice.
References
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2. Agapakis CM, Silver PA. Synthetic biology: exploring and exploiting genetic modularity through the design of
novel biological networks.
Mol Biosyst
. 2009;5(7):704
713.
3. Purnick PE, Weiss R. The second wave of synthetic biology: from modules to systems.
Nat Rev Mol Cell Biol
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2009;10(6):410
422.
4. Tigges M, Fussenegger M. Recent advances in mammalian synthetic biology-design of synthetic transgene control
networks.
Curr Opin Biotechnol
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460.
