Synthetic Biology: Engineering Organisms for Health Applications (www.kiu.ac.ug)

Synthetic biology represents a transformative convergence of biology and engineering, enabling the
design, modification, and construction of biological systems to perform novel and useful functions. In
health and medicine, synthetic biology holds tremendous promise for developing next-generation
diagnostics, therapeutics, vaccines, and biosensors. This paper examines the evolution, core principles,
and tools of synthetic biology, highlighting its interdisciplinary roots and its application to microbial
engineering, genetic circuit design, metabolic pathway optimization, and computational modeling. Recent
advances are discussed through key case studies, including engineered probiotic bacteria for gut health,
one-shot synthetic vaccines, and tumor-targeting bacteria. The review also addresses ethical concerns,
biosafety, and emerging regulatory frameworks crucial for the responsible deployment of synthetic
biology. The integration of cell engineering, software-aided biological design, and metabolic rewiring is
forging new pathways for precision medicine, offering safer, more effective, and programmable medical
interventions. While the future is promising, the field must carefully navigate biological complexity,
potential ecological risks, and public trust.

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Synthetic Biology: Engineering Organisms for Health
Applications
Katu Amina H.
School of Natural and Applied Sciences Kampala International Uganda
ABSTRACT
Synthetic biology represents a transformative convergence of biology and engineering, enabling the
design, modification, and construction of biological systems to perform novel and useful functions. In
health and medicine, synthetic biology holds tremendous promise for developing next-generation
diagnostics, therapeutics, vaccines, and biosensors. This paper examines the evolution, core principles,
and tools of synthetic biology, highlighting its interdisciplinary roots and its application to microbial
engineering, genetic circuit design, metabolic pathway optimization, and computational modeling. Recent
advances are discussed through key case studies, including engineered probiotic bacteria for gut health,
one-shot synthetic vaccines, and tumor-targeting bacteria. The review also addresses ethical concerns,
biosafety, and emerging regulatory frameworks crucial for the responsible deployment of synthetic
biology. The integration of cell engineering, software-aided biological design, and metabolic rewiring is
forging new pathways for precision medicine, offering safer, more effective, and programmable medical
interventions. While the future is promising, the field must carefully navigate biological complexity,
potential ecological risks, and public trust.
Keywords: Synthetic biology, genetic engineering, metabolic engineering, cell-based therapy, CRISPR,
biosensors, synthetic circuits, biocontainment.
INTRODUCTION
The current success of synthetic biology sets it apart from traditional biological engineering perspectives.
Despite theoretical advancements, synthetic biology has not yet achieved the foundational understanding
or capabilities found in electronic or software engineering. Unlike these fields, synthetic biology lacks
rapid prototyping, reliable operation, and modular construction. The focus is on the metabolic systems of
individual cells, whether prokaryotic or eukaryotic, which are highly complex. Simple unicellular
organisms function with around a million components, while multicellular entities exhibit even greater
complexity, with up to ten billion components. The interactions of cellular components give rise to
behaviors like cognition and decision-making. These biological systems showcase capabilities that
outstrip current engineered systems, posing significant scientific questions about their underlying
mechanisms and design principles. Understanding these phenomena is crucial, and synthetic biology
techniques could greatly aid in this exploration [1, 2].
Historical Context and Development
Modern synthetic biology finds its origins in the history of physiology from the mid-19th century to the
mid-20th century. An important milestone was the advent of Mendelian genetics, the rediscovery of
which in 1900 marked the birth of the science of genetics. The analyses of inheritance patterns through
the crossbreeding of living forms explained a wide variety of biological phenomena. The July 1953 issue
of Nature featured an article entitled “Molecular Structure of Nucleic Acids: A Structure for
Deoxyribonucleic Acid,” which reported on the elucidation of the DNA helix by James Watson and
Francis Crick. Since the mid-20th century, a trove of information concerning genetic heredity and the
machinery for DNA/RNA/peptide/ protein metabolism has become available as a result of a concerted
effort by biologists. The existence of the genetic code containing triplet codon/anti-codon matching rules
to explain the sequential translation of mRNA into peptides was proposed and experimentally verified.
EURASIAN EXPERIMENT JOURNAL OF BIOLOGICAL SCIENCES (EEJBS)
ISSN: 2992-4138 ©EEJBS Publications
Volume 6 Issue 3 2025

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Engineering approaches to understanding life had been initiated in laboratories around the same time.
The term “synthesis” as a means to understand biological systems was adopted generally. Jacques Loeb, a
US-German biologist who investigated the mechanisms of parthenogenesis and negative tropism in
marine animals, had begun using “synthesis” in his work by the late 1890s. “The coming of the synthetic
biologist” was a headline in the Boston Herald in June 1899, referring to Loeb’s work. The term “creation
of life” was popularized. An experiment employing a mixture of chemical reagents capable of exerting the
physiological activities prevalent in living organisms in a living-free test-tube system became known in
his later work, elaborating a new mechanical basis for the first principles toward a cell mechanism. In
these early years of the 20th century, engineering approaches relied on taking advantage of the laws of
physics and chemistry to explain life phenomena in terms of engineering equations [3, 4].
Core Principles of Synthetic Biology
Though synthetic biology is a new term, many of the ideas behind it have been explored long before it
came into formal existence in 2000. The word “synthetic” implies constructing something new, while
“biology” implies understanding existing systems. Synthetic biology combines these two concepts to
engineer organisms as systems. Biology largely focuses on sequencing genomes or characterizing
biological systems, whereas synthetic biology is dedicated to the engineering of systems. A wide search is
conducted by many research communities for novel chemical, metabolic, or anatomical parts to be
integrated into future engineered circuits. The basic goal of synthetic biology is to design and construct
an organism to enact a programmed behavior. To meet this grand ambition, engineering methodologies
utilized to design and construct non-biological systems must also be employed in the biological domain.
Some engineering elements are already present in parts that perform natural functions. So far, these
components have sold themselves in nucleotide databases. Yet, the diversity present in nature is
insufficient. Whole systems, whether engineered or not, are far too complex, even for the simplest
organisms. Standard parts, components, and devices must be modularized to build larger systems. Hence,
some design rules will need to be modified significantly. Theory development will need to start anew,
devising fundamentally new principles and mechanisms to capture biological function dynamics. These
are not at odds with control, information, or communication theories now in use but are utterly different
ways of abstraction at various levels of resolution. Fundamental questions, such as whether biological
systems can be engineered and why engineering principles in the biological domain appear fundamentally
different, remain fascinating challenges for the younger scientific community. Primary elements
associated with engineered biological systems, including parts, devices, and systems, are now under
discussion. Similarly, how they are implemented in tandem will be addressed, first at the interface
between the host and engineered circuits, devices, and systems, and then, if needed, at the systems level.
On the micro-engineered components, their ongoing developments are described, which bring versatile
and unprecedented possibilities [5, 6].
Genetic Engineering Techniques
To design genetic engineering tools for bacteria and yeast, a rigorous framework of rules for genetic
regulatory circuits in higher organisms must be established first. Techniques for E. coli and S. cerevisiae,
such as RNA-based switches and CRISPR-based methods, can detect and respond to various molecules
and integrate transgenes precisely. CRISPR RNA-guided techniques manipulate biochemical reactions in
these organisms and control targeted cell fate and proliferation. The commercial impact of metabolic
engineering on fine chemicals and fuel production has led to a second wave of synthetic biology based on
building blocks and Evolution, inspired by natural modularity and cellular systems. This view examines
modularized molecules and compartments, integrating evolutionary achievements and triggering
nanostructured probes with controllable dynamics. Microbiota, an assemblage of microbes and genes in
specific environments, differs from the microbiome. Human microbiota, found from the skin to the
gastrointestinal tract, play essential roles in health. However, genetic engineering tools for studying non-
model gut microbes are limited. Engineered gut bacteria can be delivered live to perform programmed
functions and distinguish between healthy and diseased states. This could aid in phenotyping poorly
understood microbes and developing a synthetic biology toolbox to enhance the probing and alteration of
diverse non-model gut microbes, potentially creating synthetic consortia of gut bacteria to prevent or
cure diseases [7, 8].
Metabolic Engineering
Metabolic engineering focuses on the design and implementation of engineered biological systems with
predetermined properties and functions that can increase chemical production. The production of
chemicals and compounds of interest using engineered microbes instead of extracts or bulky

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chemocatalysts ensures better cost-effectiveness and reduction of environmental impacts. The methods
that provide reconstructive, constructive, or destructive genome modifications with fine-tuned precision
at the nucleotide level are employed. These techniques usually depend on DNA parasites or nucleic acid
enzymes, commonly referred to as ribozymes or deoxyribozymes. Bioconversion of renewable carbon
sources (ideally organic wastes) into high-value products allied with renewable energy is a topic of great
environmental importance. Metabolic engineering of recombinant microorganisms offers an efficient
alternative for the chemical production of fuel and other valuable compounds from low-cost lipids. The
important pathways of microbial lipogenesis and beta-oxidation have been unraveled, and as a strategy
for the construction of a synthetic biofuel production strain, their key enzymes have recently been
successfully overexpressed or engineered in bacteria or yeast models. Besides energy, bioethanol
production is also a topic of great interest, and several strains have been engineered to efficiently ferment
depleted plant biomass in aqueous or ionic liquids. For the polymerization of sugar/nucleotides and
amino acids, as well as for de novo biosynthesis of pyrimidine and purine, unprecedented metabolic fluxes
in the lower half of central metabolic pathways have been redirected in bacteria, thus globally increasing
the intracellular pool levels of desired precursors. Several principles governing the wide acceptance of
microorganisms as cell factories have been summarized. Bacterial and yeast strains as cell factories
accommodate large plasmids replicating in the high copy number, and gram-negative bacteria are more
amenable to heterologous gene expression, thereby offering a wider base of codon-optimizing options for
highly GC- or AT-rich genes for better expression efficiency [9, 10].
Synthetic Biology Tools and Software
Synthetic biology combines disparate disciplines, including molecular biology, mathematics, engineering,
physics, bioinformatics, and computer science. Scientists across disciplines exploit the accessibility of
biotechnological techniques to systematically engineer, redesign, and recreate biological organisms for
diverse applications in medicine and energy. Early efforts in synthetic biology focused on assembling
short DNA fragments or oligonucleotides and inserting them into plasmids for recombinant protein
expression. New computational and experimental techniques now enable the generation of large synthetic
or semi-synthetic biologically active arrays made of nucleic acids, proteins, RNA nanostructures, and
metabolic pathways with possible therapeutic or bioenergetic applications. Synthetic biologists use
various computerized and experimental tools to validate mathematical models, record, and visualize
physiological states, and generate synthetic DNA and protein constructs. DNA plasmids, code-encoding
sequences, gene synthesis, and in-house or commercial biofoundries design DNA constructs de novo.
Several open-sourced and commercial software and algorithms systematically design large numbers of
synthetic DNA constructs encoding diverse or complementary variations of biological systems. New
assembly and cloning techniques facilitate rapid, high-throughput assembly of synthetic fragments and
their cloning into plasmids. Experimental techniques exist to characterize, record, and visualize
physiological states such as fluorescence, gene expression data, cellular morphology, and behavior. New
synthetic devices sense states and selectively regulate large numbers of endogenous genes in prokaryotic
and eukaryotic cells. New bioreporters and methods limit and visualize the biosynthesis of diverse
metabolites in label-free real-time assays. Novel methods exist to precisely cut and light-activate multiple
large DNA fragments, e.g., ∼40 kb long, genes and synthetic circuits, and append DNA or protein tags to
large synthetic constructs or whole cells. New computer programs generate visual static and dynamic
circuits using distributed-chip photolithography methods or transistor-transistor logic circuits.
Innovative chip designs distribute DNA on the chip surface using an origami-based three-dimensional
design, as opposed to ubiquitous two-dimensional designs. Scientists can progressively and
simultaneously create synthetic devices, systems, and circuits of diverse variations and complexities from
entry to industrial scales by linking several of these computational and experimental tools [11, 12].
Applications in Health and Medicine
Synthetic biology (SB) applies a variety of engineering principles and techniques to the assembly of
biologically functional parts. As a new interdisciplinary research discipline, SB integrates components
from various biological and non-biological sources, such as computer science, electronics, mathematics,
chemistry, and biology, and at various organizations, from DNA sequence control with computer-aided
design software to cell metabolism control with fully characterized synthetic switches, to design
engineered cells or living organisms that can carry out desired functions. Health and medicine a broad
and important fields aiming to improve human health with more effective and safer medical diagnostics,
treatments, and drug development. With a unique advantage as a well-established and fast-growing
research discipline, SB can apply a variety of rational designing and engineering strategies to facilitate the

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development of next-generation diagnosis, treatment, and drug development. Cell engineering plays an
increasingly important role in SB-oriented health and medical applications. Engineered cells have shown
great potential to become powerful and flexible medical devices for effective diagnoses and therapies with
low or no side effects. Various SB-inspired innovations have been developed to modify cell metabolism to
produce a range of biocompatible, biodegradable, and bioresponsive nanomaterials. The synthetic gene
circuits are designed through rational engineering approaches to regulate the expression of transgenes
and thus cellular behaviors. Cell engineering can be used to develop cell-based treatment platforms that
can be modified, expanded, and programmed to regulate treatment performance. The exogenous genes
inserted and/or pathways reprogrammed in such cells can be adjusted to produce therapeutic proteins
and small molecules. Cell engineering-based innovative tools can be utilized to design smart cell-based
sensors and therapies. However, challenges remain to be solved, such as delivering engineered cells into
the human body. This review summarizes representative SB-driven devices in each category of health and
medical applications, including the recent advances, benefits, limitations, and prospects of SB-inspired cell
engineering in diagnosis, treatment, and drug development [13, 14].
Ethical Considerations
Synthetic biology (SynBio) will affect human life in various ways. The basic premise of SynBio is to
design, construct, and modify a biological molecule, cell, or organism to perform certain pre-determined
tasks. Some of the major objectives of SynBio research include the production of biofuels, food,
pharmaceuticals, and biomedical technologies. Thus, applications of engineered organisms will address
the global challenges of food, energy, environment, and health. SynBio is expected to have a large impact
on human health in the next decade by providing inexpensive vaccines, biosensors for disease diagnosis,
and engineered probiotics that improve enteric health. Many health applications using engineered
microbes for live biotherapeutic and early detection of diseases are already under development and have
reached animal testing stages. Although several products are awaiting entry into clinical trials, guidelines
for their regulation are still being elaborated. Seen as advantageous when compared to traditional
approaches, these innovations in engineering organisms nevertheless raise concerns relative to
environmental and public safety. In particular, the use of genetically modified (GM) organisms in open
settings or humans in uncontrolled conditions poses many questions about their containment: four
biosafety levels exist depending on the pathogen's virulence, and new engineered mechanisms could be
developed. The dilemma is whether it is better to design an organism able to survive and perform a
determined task in a given environment or to expect to use and discard it. Indeed, containment might
always be imperfect, programming an organism to die after some hours of exposure to a specific signal
might be a solution; however, what if the signal is not reaching the organism? It has already been
proposed in the case of environmental bioremediation that engineered microbes could give rise to new
uncontrollable superweeds by undergoing lateral gene transfer with other organisms. It is too early to
conduct a foresight analysis of future illnesses due to engineered organisms, however, and many experts
warn against expecting doom scenarios similar to those raised by environmental GMOs. On the other
hand, engineered organisms may have been part of human health improvement for many years. Informal
Codex Guidelines were developed to ease their commercialization; however, they cannot contend with
formal codes of conduct for advanced and more restrained biotechnology developments [15, 16].
Regulatory Framework
Biotechnology and synthetic biology (SynBio) have raised concerns of uncertainty and risks to health and
the environment. We focus on engineered microorganisms in industrial biotechnology (IB), which
promises decreasing environmental impacts, positive socioeconomic effects, competitive processes and
products, and development in rural areas. The last decade has seen impressive technological
achievements, including the synthesis of bacterial genomes, the development of computer-aided systems
for logic circuit construction in bacteria, the CRISPR genome editing revolution, and the use of non-
natural building blocks and non-canonical chemistry leading to xenobiology. These developments have
introduced concepts of trophic and semantic containment of engineered microorganisms, enabling safety
as an inherent feature. The idea of genetic safeguard technologies for biosafety has re-emerged. Since the
beginning of synthetic biology, synthetic biologists have embedded bio-containment mechanisms in
organisms engineered to live in industrial settings. This desire for engineered organisms not to survive
outside industrial settings has inspired much research into bio-containment technologies. Some biological
mechanisms have already entered industry today as safety mechanisms, but are still simple ones, such as
scaffold-based ones. There is a host of complex bio-containment systems that require research effort in
parts production, parts characterization, and organism engineering to be operational. Therefore, these

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systems will likely be available in industrial settings in the coming decade. This allows societal
engagement about the risks associated with complex bio-containment systems. In addition, bio-
containment technologies will only be effective based on certain preconditions [17, 18].
Case Studies
Each of these synthetic biology applications will be explored, focusing on engineering strategies to create
designer biology and disease targets. Case studies will illustrate how synthetic biology, systems biology,
and microorganism engineering contribute to cell-based therapies. A revolutionary one-shot vaccine for
anthrax has been developed using synthetic biology and visualized by scanning electron microscopy. This
vaccine could substitute conventional vaccines and is a designer two-part anthrax vaccine based on
eNanobodies and ePseudo carriers, constructed entirely in silico using a sequence-based technique. The
synthetic vaccine features a multilayered nanoparticle structure for anthrax toxin adsorption and delivery
via cellular uptake. Monocytes are effectively recruited to the site, resulting in enhanced humoral
immunity with high titers of neutralizing antibodies, improving survival in animal models. This vaccine
shows resilience against complex cellular machinery, presenting a robust synthetic design for practical
applications despite immunity not being a typical priority in synthetic biology. The rising prevalence of
malignant tumors requires improved delivery of therapeutic agents. A synthetic biology approach
engineered an E. coli bacterium for organ-specific migration to solid tumors. By sensing hypoxia in the
tumor microenvironment, regulators and coding genes were integrated into the bacterium, enhancing
kynurenine pathway metabolite biosynthesis, affecting tryptophan catabolism, and promoting tumor
growth. The bacteria sequester tryptophan by producing indole through tryptophanase, while derivatives
transport to elevate tumor ROS levels. This method offers insight into inhibiting tumor growth and
provides an efficient avenue for specialized tumor therapy through microbial symbiosis [19, 20].
Future Trends in Synthetic Biology
The re-emergence of synthetic biology is leading to the engineering of organisms for performance, safety,
and accessibility. In the next decade, living technology will become robust and affordable, becoming
mainstream in homes, schools, and workplaces. Engineered organisms will produce consumer goods, offer
living therapeutics to treat diseases safely, and grow food at home. Synthetic organisms will recycle waste
into new products, bringing science fiction concepts to reality, alongside ethical and safety discussions.
The rise of synthetic logic devices similar to current electronic logic gates will allow for the design of
networks with integrated parts. Advances in computing and algorithms will enable the modeling of
complex systems. Synthetic devices in cells will facilitate cellular circuitry for decision-making processes.
The construction of organisms capable of navigating varied environmental conditions will utilize XOR
gate strategies, managing multiple inputs. Devices will enhance signal propagation in cells, modulating
responses to environmental signals and releasing synthesized outputs, such as RNA or proteins, paving
the way for synthetic biology's future by 2030 and beyond [21, 22].
Collaboration between Disciplines
The discovery of DNA's double helical structure, though celebrated, exposed longstanding limitations of
this macromolecule. The nucleotide sequence isn't a decipherable code akin to software. Molecular
interactions remain complex and elusive to scientists. Simply transcribing known templates can lead to
chaos. Synthetic biology emerged as a solution, requiring a chemical mathematics framework to control
chemistry and prevent unpredictable reactions. It combines molecular biology, genetic engineering,
computer science, and more. Phylogenetic studies suggest the last universal common ancestor existed
over 3.8 billion years ago, but whether life as understood today was present remains debatable. Life
creation demands not just self-replicating molecules but also understanding their interactions in
primordial conditions, imposing high computational demands on genomes. Current capabilities fall short.
Interestingly, a ring of ten small ribozymes may stabilize pricing cycles and magnify changes, offering
insights into historical molecular evolutions and errors post-LUCA formation. Dramatic replication
errors hindered pre-programmed genetic selections. Engineering genomes showcases our limitations in
understanding various pathways and formations, with viral genome types estimated in the billions. This
complexity indicates that cellular regulation and programming are more intricate than anticipated. Man-
made DNA and RNA synthesis has yet to identify candidates fitting these high-level metabiotic domains.
Chemists and engineers must determine how biology originated and how chemistries evolved into
genomes and organisms [23, 24].
Funding and Investment in Synthetic Biology
Over $2.6 Billion Was Invested in Synthetic Biology Within the Last Four Years. The Unprecedented
Growth of Synthetic Biology Is Attracting Interest From Government Funders and Venture Capitalists

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Alike. Together, They Are Banking on a Future Where Synthetic Biology Will Play an Industrial and
Societal Role. Many Aren’t Fully Comprehending the Request. As the Synthetic Biology Industry Grows
Up, an Ecosystem Is Beginning to Emerge. The Early Investors Considered Synthetic Biology Too
Precocious and Pulling It Out of the Shallows Too Early Destabilised the Industry. In the UK, This
Hampered the First Move in Addressing the World’s Grand Challenges Using Synthetic Biology and
Almost Crippled the UK’s Academic Centers of Excellence. Something Different Is Now Appearing. The
’Picks and Shovels’ Mindset Is Now Respected, and the Equipment Manufacturers, Platform Companies,
Off-the-shelf Technologies Are Broader Than Just Foundry Services Companies Will Win. It’s Time for
Vivo and in Situ Applications. The Last Four to Five Years Have Changed the Game Perhaps More Than
in the Previous 15. Synthetic Biology Is Slow to Gather Momentum and Even Slower to Attract Real
Money. Two Decades of Investment in Equipment and Development of Investment Infrastructure—the
Pie Is Not That Much Bigger. Data and Data Ownership Are King; Companies With the Most Data on a
Given Biome Will Win. Somebody Will Need a Terminator Strategy and Horizon Scanning on
Biohacking and What Happens When a Part Gets Out! [25, 26].
Public Engagement and Education
Public education and engagement in synthetic biology may be driven by both the scientific community
and NGOs. Reports on the ethical aspects of synthetic biology and discussions across disciplines and with
various stakeholders were presented. The symposium included two outreach talks to the general public
and a “Breakfast with the Professors” event at which symposium speakers interacted with high-school
students (e.g., answering questions about science, technology, bioethics, and career paths). The same
considerations apply to mass media. Science journalists, newspaper columnists, and, more recently, blogs
or podcasts, and science activists like various NGOs all play an important role in the dissemination and
examination of scientific developments. Novel biotechnologies range from routine applications of
standardized bioprocesses to much more sophisticated applications using GMOs. These developments are
followed by the mass media, sometimes leading to excessive expectations or public fears. Ethical issues
intrinsic to synthetic biology are its potential for misuse and the possible development of bio-weapons.
Synthetic biology raises other ethical questions that are more similar to those raised by GMOs’
technology, such as designer organisms, commercial versus social exploitation, and ownership of bio-
patents. These issues need to be taken into consideration in media outreach as well. The media reflect the
dialectic nature of science and society, which becomes clear again when the HGP and first synthetic
microorganisms are considered [27, 28].
CONCLUSION
Synthetic biology is revolutionizing the way we understand, manipulate, and utilize living systems for
human health applications. From designing programmable cells to creating synthetic vaccines and
disease-targeting bacteria, this interdisciplinary field enables precision interventions that were once
unimaginable. However, as the power of synthetic biology grows, so too does the need for stringent
ethical, safety, and regulatory considerations. Balancing innovation with responsible stewardship will be
critical in ensuring that engineered organisms contribute positively to health systems and society at
large. With continued advancement in tools, frameworks, and public engagement, synthetic biology has
the potential to redefine the future of medicine, making it more precise, proactive, and personalized.
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CITE AS: Katu Amina H. (2025). Synthetic Biology: Engineering Organisms for Health
Applications. EURASIAN EXPERIMENT JO URNAL OF BIOLOGICAL SCIENCES 6(3 ):100-
107