Synthetic biology is a field that aims to design and engineer biological organisms and systems for useful purposes. It involves modifying organisms to have new abilities by redesigning their DNA. Some key goals of synthetic biology include producing medicines, manufacturing chemicals, and solving environmental problems in eco-friendly ways. It differs from genetic engineering in aiming to make more extensive and predictable changes at a larger scale, such as designing whole new genomes. Synthetic biologists use techniques like DNA synthesis and standardization to achieve their goals. Recent advances include using synthetic biology to sense environmental conditions, produce chemicals, and even create artificial enzymes not found in nature.

1. MBB-591
Presented by – Samrity Sharma (H-2018-56-M)

2. Outline
• What is synthetic biology?
• Why synthetic biology?
• Aims of synthetic biology and how it is different from genetic
engineering?
• Approach
• Principles
• Synthesis of DNA artificially.
• Popular issues.

3. Introduction
Biotechnology has become a major supporting technology in the 20th century. A relative
recent development within biotechnology is the emergence of the field of synthetic
biology.
Biotechnology is a broad term encompassing the application of biological components or
processes to advance human purposes whereas Synthetic biology refers to a set of
concepts, approaches, and tools within biotechnology that enable the modification or
creation of biological organisms.

4. • Although academic interest in synthetic biology has gained significantly
over the past decade (Oldham, Hall, & Burton, 2012), scientists have been
debating over its meaning for over a century.
• In the past 100 years, synthetic biology was used in both conceptual and
practice orientated discussions, describing in various degrees to what extent
biological systems could be exploited.

5. History in brief.
• In 1912, both Stéphane Leduc (Leduc,1912) and Jacques Loeb (Loeb, 1912) mentioned
synthetic biology in speculations over possibilities to create artificial living systems.
• Later on, in 1974, Waclaw Syzbalsky mentioned synthetic biology to describe the application
of recombinant DNA technology to generate organisms with new genetic properties (Benner,
2010).
• Around a decade ago, the concept started to be used to refer to the synthesis of unnatural
molecules (Rawls, 2000)(Sismour & Benner, 2005), unnatural chemical systems (Benner &
Sismour, 2005), biology-inspired systems (Pleiss, 2006), and functions not existing in nature
(Serrano, 2007).
• The first artificial cells were developed by Thomas Chang at McGill University in the 1960s.
These cells consisted of ultrathin membranes of nylon, collodion or crosslinked protein whose
semipermeable properties allowed diffusion of small molecules in and out of the cell. These
cells were micron-sized and contained cell, enzymes, hemoglobin, magnetic materials,
adsorbents and proteins.

6. Semi-synthetic drug
artemisinin.
In 2003, Jay Keasling and his team at UC
Berkeley announced success story of
synthetic biology.
They had successfully implanted genes into
yeast that produces a precursor to the
antimalarial drug artemisinin.
Though the disease can be treated with
antimalarial drugs, there is limited access to
medical care in the poorest of the affected
regions They use synthetic biology to
develop strains of Saccharomyces cerevisiae
(baker's yeast) for high-yielding biological
production of artemisinic acid, a precursor
of artemisinin.

7. ARTIFICIAL CELL.
• Daniel Gibson at the J. Craig Venter Institute in Rockland, Maryland, and his colleagues in
2010 began with a highly accurate genome sequence they had made of the bacterium
Mycoplasma mycoides.
• Using this as a template, they ordered a set of short DNA strands called 'cassettes', each about
1,000 base pairs long, from a DNA-sequencing company, then inserted the cassettes into a
yeast cell, where the yeast's own genetic machinery strung them together into a copy of the
natural M. mycoides genome.
• Finally, the researchers transplanted the 1.1-million-base-pair-long synthetic genome into
cells of a closely related bacterial species, Mycoplasma capricolum. Although only the
genome of the new cell was custom-built, the researchers refer to the entire cell as "synthetic"
because its molecular contents quickly took on the characteristics of M. mycoides. "By
changing the chromosome in the cell, it completely changes the cell from one form to
another," Venter said in a press briefing .

9. What is Synthetic Biology?
Synthetic biology is a field of science that involves redesigning
organisms for useful purposes by engineering them to have new
abilities. Synthetic biology researchers and companies around
the world are harnessing the power of nature to solve problems
in medicine, manufacturing and agriculture.

10. Synthetic biology (SynBio) is an
interdisciplinary branch of biology
and engineering.
Decreasing costs of DNA
synthesis and recent advances in
technology have fueled the success
of synthetic biology companies in
recent years, and now comprises
one of the fastest growing and
most funded areas of commercial
biotechnology.

13. COMPANIES PRODUCING SYNTHETIC DNA

14. Why synthetic biology ?
Cells can make copies of themselves : Many of the challenges that synthetic biologists are
targeting can be addressed by other engineering disciplines, such as electrical, chemical, or
mechanical engineering, but synthetic biology’s solutions offer a few unique advantages as cars
can’t copy themselves it needs a factory to build a car.
Also, some organisms can copy themselves incredibly quickly, even with minimal nutrients. For
example, in the lab, the bacterium E. coli can replicate and divide in about 30 minutes. Therefore,
synthetic biology is an attractive approach for producing large amounts of a specific product
because we can grow a programmed cell relatively easily to meet large-scale production demands.

15. Cells contain the biological machinery to carry out many complex tasks—
specific chemical reactions, for example—that would be difficult, if not impossible, to
accomplish otherwise. And, they do so with nanoscale precision that is difficult to replicate
in any traditional fabrication facility. Also, when their nanoscale machinery breaks, cells
have mechanisms to repair themselves, at least to some extent, which puts them at a great
advantage over more typical factory-based production processes. Cellular complexity
introduces its own hurdles to be considered, as well, but its potential utility is enormous.
Synthetic biology has the potential to produce eco-friendly solutions to many difficult
problems. By necessity, the byproducts of synthetic biology applications are generally
nontoxic, because most toxic compounds would kill the very cells that are doing the work.
In addition, harnessing natural cellular systems often results in economical processes.
Today’s industrial production of compounds consume large quantities of energy, often
creating significant amounts of environmentally harmful waste and frequently requiring
high temperatures or pressures.

16. Beyond its usefulness for addressing real-world challenges, synthetic biology is
also a fantastic approach to learn more about the workings of natural systems.
As researchers dissect increasingly complex cellular functions, they can use
synthetic biology to test their hypotheses from additional angles.
For example, if their biochemical research results suggest that a certain protein
acts as a sort of on/off switch, they can test this result by replacing the existing
protein with a protein that is known to exhibit on/off behavior. If the new
synthetic system and the natural system behave similarly, the result provides
further evidence that the natural protein acts as the researchers suspected.

17. Aims of synthetic biology
The goal of synthetic biology. Synthetic biologyaims to write DNA
(left) that instructs a cellor organism(right)to behaveaccording to
design specifications.
• At the most basic level, synthetic biology
aims to engineer living cells to do
something useful like treat a disease, sense a
toxic compound in the environment, or
produce a valuable drug.
• As Figure suggests, synthetic biologists
achieve these outcomes by altering an
organism’s DNA so that it behaves
“according to specification”.
• Craig Venter, for instance, is working to
develop bioreactors in which algae cells
convert carbon dioxide from the atmosphere
into fuel.

18. Synthetic biology today. Currently, synthetic biologists generally design a portion of DNA (left) and combine
it with an existing cell or organism (middle) so that the new cell or organism (right) behaves according to
design specifications.
• We can think of cells as complex miniature factories, hence by employing cells to produce or synthesize a
particular product we can make it a more eco friendly process .
• DNA provides instructions to make all the machines in the factory — proteins, nucleic acids, multicomponent
macromolecular complexes, and more. These “machines” then carry out the work of the cell. The organism’s
naturally occurring DNA allows the cell to meet its basic survival and reproductive needs. Synthetic biologists can
change a cell’s DNA so that the cell takes on new, useful functions.

19. • An illustrative—example of synthetic biology’s
potential scale is the genetic reprogramming of a tree
so that it will grow into a fully functional house based
on the genetic instructions designed by a synthetic
biologist. Such a system would take advantage of the
tree’s natural program (to grow by taking in a few
nutrients from the environment) and put it to use for
society’s needs. Genetically programming a tree to
grow into a house, however, is far beyond the scale
of traditional genetic engineering as well as the
capacity of synthetic biology at this point.

20. Difference between synthetic biology and genetic
engineering.
1. Synthetic biology and genetic engineering differ in the scale at which they aim to
make changes.
2. Genetic engineers are usually introducing one or two small changes to investigate a
specific system, whereas synthetic biologists aim to design new genomes and
redesign existing genomes at a grand scale

21. Genetic engineering.
• Genetic engineering includes
recombinant DNA technologies
and molecular cloning
(Abdullah et al., 2014). With
modern genetic engineering, it
is possible to recombine, cut
and paste genes from one
organism into another target
organism.
Synthetic Biology
• The application of various scientific
and intellectual areas to design and
create full genetic systems that can
be implemented in an organism in
order to perform a self-regulated
task. This does not imply just
recombining DNA, but designing
and modeling a novel pathway by
assembling many different pieces of
genetic material collected and
characterized from natural
organisms.

22. “now a powerful form of genetic engineering could revolutionize the
production of some of the most sought after flavors and fragrances” ( 21
October 2013, The New York Times)
More purpose driven
science
“Synthetic biology aims to allow more extensive changes , and in a more
efficient and predictable way” ( 5 September 2010, The New York Times)
Allows for more
predictability
“this also entailed building the bacteria itself-redesigning a living
organism, using the tools of a radical new realm of genetic engineering
called synthetic biology” (14 Feb 2010, The New York Times
Creates new organisms instead of
simply relying on tinkering with
naturally occurring ones

23. Fundamental approach
• Synthetic DNA synthesis.

24. The Synthetic Biology Toolkit
Molecular biologists have spent years developing methods to manipulate DNA in different ways. Following
are three of the most crucial and well-established techniques, which are used extensively in synthetic biology:
• Reading the DNA code
• Copying existing DNA sequences
• Inserting specific DNA sequences into existing DNA strands
Tool Molecular biology
technique
Natural cellular process
Reading DNA Sequencing DNA replication
Copying DNA PCR DNA replication
Inserting DNA rDNA with restriction
enzymes and ligases
Defense from infection,
DNA recombination and
repair
The molecular biologytoolkit and its natural origins

25. The Tools Expanded for Synthetic Biology
• Although methods used in molecular biology have been around for many years and
have been used to great effect in research, they are not sufficient for synthetic biology.
They might be sufficient to insert a gene from a chameleon into a plant, for example,
but they would not enable the reliable reprogramming of a plant to grow into a house.
• Consequently, we use the term genetic engineering, not synthetic biology, to refer to
the relatively small-scale manipulation of genes in a host organism, perhaps altering at
most a handful of genes.

26. To achieve more ambitious engineering goals, synthetic biologists
expand their toolkit beyond that of traditional genetic
engineering to also include design principles from the more
established engineering disciplines
• Theseadditional tools, which are still largelyin
development, include:
• standardization, abstraction
> Bothstandardization and abstraction are
directly drawnfromthe toolkits of other
engineering disciplines, whereas DNA synthesis is
an engineering tool unique to syntheticbiology.

27. Standardization
• Standardization is a key attribute of mature engineering disciplines because it makes it
possible for engineers to more quickly implement exciting, innovative, and useful
solutions.
• Standardization is a crucial part of any engineering discipline because it facilitates
designers being able to reuse parts, combine efforts with other teams, and work
efficiently.
• For synthetic biologists, standardization enables small pieces of DNA to be
physically and functionally connected.

28. Standardization

29. Abstraction
• Through abstraction, synthetic biologists can design complex parts,
devices, and systems without worrying about every detail of how they
work. Instead, the focus is on the end goal, which is the final system
output or behavior.
• Abstraction is an important aspect . It allows us to think about and
communicate our plans without becoming bogged down in the details all
at once.
• Some useful abstraction levels for designing a new synthetic organism
includes: systems, devices, parts, and DNA.
• It is the enumeration of many biological parts, as well as the reliable
composition of these parts.

30. DNA synthesis
• Synthetic biologists are often designing new sequences for which no template
exists. When there is no template strand to follow, they determine the nucleotide
order of the synthetic DNA by using digital sequence information. With this
technology, synthetic biologists can write new DNA sequences that have never
been written before.

31. Recent Advaces of synthetic biology
• Sensing environmental conditions: e.g. ecosystem contaminants, metabolic conditions
or explosives.
• Combat infections or delivery at Nano-scale level
• Contributing in production of existing and novel bio based chemicals and products: e.g.
production of chemicals.
• The synthetic biology initiative known as Human Genome Project-write (HGP-write),
rallying scientists to build entire human chromosomes (Boeke et al.,2016).
• System biology.
• Minimal cells.

32. World’s first artificial enzymes created using
synthetic biology:
Professor Philipp Holliger’s (MRC Laboratory of
Molecular Biology, Cambridge) team have created
the world’s first enzymes – ‘XNAzymes’ – made
from artificial genetic material not found anywhere in
nature. This was published on 01 Dec 2014
Because this XNAzymes are much more
stable than naturally occurring enzymes, this
synthetic biology approach could provide a starting
point for an entirely new generation of drugs and
diagnostics for a range of diseases, particularly useful
in developing new therapies against cancers and viral
infections which exploit the body’s natural processes
to take hold in the body.

33. Enzymatic Menthol Production(January 2018)
Menthol isomers are high-value commodity chemicals, produced naturally by mint plants.
The high demand by the flavor and fragrance industries for natural sources has a high cost in terms of
arable land use and expensive distillation and filtration processes, which means that alternative clean
biosynthetic routes to these compounds are commercially attractive.
Researchers at the University of Manchester
have engineered E. coli to efficiently convert
pulegone (an essential oil produced by a variety of plants)
to menthol. They demonstrated that ketosteroid isomerase
(KSI) from Pseudomonas putida can act as an IPGI
Using a robotics-driven semi rational design strategy KSI
variant was demonstrated to function efficiently within cascade
biocatalytic reactions with Mentha enzymes pulegone reductase and (−)-menthone:(−)-menthol

34. Caffeine-Triggered Cells Help Control Blood Sugar in Diabetic Mice
Scientists engineered human cells to produce a molecule that stimulates insulin secretion in the presence of caffeine.
• Scientists have engineered human cells that boost the production of insulin in response to caffeine. These modified
cells could one day help treat patients with type 2 diabetes
• Martin Fussenegger, a biotechnologist at the Swiss Federal Institute of Technology in Zurich and his colleagues
engineered human embryonic kidney cells that produce a synthetic version of human glucagon-like peptide a
molecule that prompts the release of insulin, in the presence of caffeine.
• Then, the team injected diabetic mice with an implant containing hundreds of the engineered cells. This revealed that
the animals’ blood-sugar levels could be controlled by simply adding a caffeinated beverage, such as coffee, cola, or
Red Bull, to their meals. Non caffeinated beverages, such as herbal tea and chocolate milkshakes, had no effect.
Jun 20, 2018 - DIANA KWON

36. Researchers Build a Cancer Immunotherapy Without Immune Cells
A team has engineered two stem cell lines into “synthetic T cells” that destroy breast cancer
cells in vitro.
Nov 13, 2017 - ABBY OLENA
• Typical immunotherapies work by harnessing the power of immune system. In CAR –T cell therapy for
example patients receive a transfusion of their own T cell that have been modified to recognize a specific
protein on the surface of cancer cells and then destroy the cancer but as we reprogram the immune system it is
having some harmful risks to cause effects.
• To engineer a similar therapeutic using other type of cells, researchers built a cancer detecting sensor in :
• HEK-293 T cell : a common cell line derived from human embryonic kidney cells.
• Human mesenchymal stem cells.
• Sensor is in two parts i.e. antenna and receptor which not only destroys the cancerous cells but also kills those
cells in the immediate vicinity of cancer cells.

37. Synthetic Stem Cells Regenerate Heart Tissue in Mice
These engineered “cells” were made from the secretions and membranes of human mesenchymal stem
cells.
Jun 1, 2017
DIANA KWON
• Mesenchymal stem cells have been tested in various clinical trials as they can promote regeneration when
injected into a tissue but there was a major limitation
• These MSC cells need to be carefully frozen to keep them alive in storage, then defrosted,
expanded and gently maintained until used .
• This process is very tedious and sometimes can affect the potency of the cell .

38. CELL TYPE MODE OF
DELIVERY
VIABILITY APPROXIMATE SIZE TESTED IN
Synthetic
mesenchymal stem
cells
Must be injected
directly into site of
action (e.g., heart)
At least one week at
room temperature
20 μm Mice
Mesenchymal stem
cells derived from
humans or other
animals
Can be injected into
blood vessels,
because they will
migrate to the site of
injury
Around 24 hours at
room temperature
20 μm Humans, in multiple
clinical trials
To overcome this problem researchers engineered synthetic MSCs which were built from human
MSC secretions packaged in a biodegradable micro particle and then coated with MSC membranes .
These synthetic MSC cells withstood harsh cryopreservation and lyophilization without loosing its
properties.

39. • Uncontrolled Release : A number of measures are being proposed or adopted to ensure adequate
biological control, including: engineering bacteria to be dependent on nutrients with limited
availability; and integration of self-destruct mechanisms that are triggered should the population
density become too great.
• Bioterrorism : A number of proposals have been made by both scientific groups and government
agencies to address the dual use (military/civilian) nature of synthetic genomics, including:
controls over commercial DNA synthesis and public research; and considering the impact of
synthetic biology on international bioweapons conventions. As yet there is no policy consensus on
these issues.
• Creating Artificial Life :One of the most potent promises of synthetic biology is the creation of
‘artificial life’. This has provoked fears about scientists ‘playing God’ and raises philosophical and
religious concerns about the nature of life and the process of creation. It has been suggested that a
stable definition of ‘life’ is impossible and that synthetic biologists are confused over what life is,
where it begins and particularly, how complex it must be