Synthetic Biology - Redrawing the Drug Discovery Map


Synthetic Biology is a powerful new tool in scientists' hands due to the recent advances in

bioinformatics, DNA sequencing, and synthetic genomics. It covers a wide range of molecular

activities involving the engineering of biological systems, manipulates chemicals, produces

energy, maintains cell environment, and enhances human health. Synthetic biology thus aims

to design and build new biological products and organisms to gain medical advantages. The

most recent example of synthetic biology is the development of mRNA-based COVID-19

vaccine, BNT162b2 by BioNTech.


As the healthcare industry turns its attention towards precision medicine and personalized

treatments for specific health conditions, synbio focuses on new microbe-based drugs and

artificial proteins for delivering medications to cells. This technique is used to generate DNA

fragments, expression vectors, or variant libraries cost-effectively and quickly.


Unlike earlier times where DNA sequence had to be cut and pasted out of an organism and put into another, synthetic biology makes it possible for you to just type your required DNA

sequence into a computer or copy it from a database. You can even select it from a catalog and then order it over the internet!


The DNA sequence may be copied from nature, but the DNA itself is made by a machine. There is an increased demand for such technologies in pharma and biotech due to the error-reduction methods that can boost accuracy to levels seen in natural polymerases and benchtop systems. Dozens of DNA fragments can now be made overnight using these techniques and result in synthesized clones and variant libraries for discovery biology, protein and antibody engineering, epitope mapping, and more.


The bug is the new drug.


Synthetic biology is playing a significant role in microbial-based therapeutics to bring out more efficacious drugs. New therapeutics are being developed based on living microbes. For

example, at CHAIN Biotech, a particular strain of Clostridium bacteria that is naturally found in

gut bacteria is now being engineered to transport drugs in the form of peptide, metabolites, or

enzymes. These are administered as capsules to be taken orally so that chronic and debilitating diseases are associated with the gut. Taking this in a tablet form makes it simple to administer and improves patient compliance.


QR code for DNA.


Octant uses synbio technologies to engage in drug discovery. It genetically engineers DNA to

act as an identifier for the most common drug receptors inside the human genome. It is

something like creating QR codes inside our genome to identify how different protein receptors act as biological sensors. This will help control many issues like immune responses, how pain is interpreted by our brains, and even the release of hormones and communications between cells in the body.


Targeted Vaccines


Prokarium, a developer of targeted vaccines and cancer immunotherapies, uses a technology

platform based on synthetically engineered bacteria. This microbial cancer immunotherapy's

beauty is that Onconella™ strain, which is a particular bacterium developed by the company,

acts by identifying the solid tumor, targeting it, and then colonizing it to exert its therapeutic

effect.


At Codex DNA, biologists working with DNA are the new software engineers. Coding and

recoding DNA is being done to advance drug discovery, vaccine development, and metabolic

engineering programs. New and more effective synbio tools can transform digital information

for vaccine into the strands of DNA.


Synthetic genome


BioXp has generated the world's first fully synthetic genome (a collection of the virus genes) for the COVID-19 virus in a short duration of ten days. This is now being broadly used for

pharmaceutical, vaccine, and diagnostics purposes. This is the world’s first and only

commercially available push-button automated platform for on-demand DNA assembly and

amplification. It can be utilized to automate the synthesis of clones, gene fragments, and

genomes to more quickly and effectively develop treatments, vaccines, and diagnostics for

many chronic diseases and cancers.


SyntheX is expanding drug design for the treatment of cancer and rare diseases. It is an

innovative platform for the accelerated discovery of new therapeutics classes that target the

Achilles' heel of cancer cells in a highly specific and selective manner. Traditional drugs work by disrupting the enzymatic function of proteins. At SyntheX, importance is given to the protein-protein interaction modulators using genetic engineering powered drug selection technology.


Artemisinin is an excellent example of synbio. This is an anti-malarial drug which naturally

produced by the sweet wormwood tree (Artemisia annua). It is challenging to complicated,

expensive, and time-consuming to cultivate. Paddon and colleagues working at Amyris, Brazil,

developed a strain of Saccharomyces cerevisiae (yeast) engineered with the entire biosynthetic pathway for artemisinic acid,5 a precursor of artemisinin. Producing genetically-modified yeast is cheaper and faster and allows significantly more widespread use of Artemisinin-based Combination Therapies (ACTs), recommended by the World Health Organization as the primary first-line treatment for malaria.


Ginkgo Bioworks define themselves as "the organism company," capable of designing and rapid prototyping a living organism with the desired characteristics. They use robots to accelerate the research and development phases of most biotech and pharma companies.


Ideaya Biosciences is an oncology-focused startup aiming to discover breakthrough synthetic

lethality medicines for genetically defined patient populations and immuno-oncology therapies targeting immuno-metabolism and innate immunity.


The future is bright


Synthetic biology uses genetic tools and techniques to design biological systems. The growing power of machine learning can be combined with synbio technology to analyze massively complex biological data to unlock new tools and platforms for drug discovery. One of the major hurdles when the bug is engineered as a drug, is safety and regulatory concerns. It is becoming mandatory that genetically modified organisms demonstrate life's safety and have a verifiable mechanism of action.


Synthetic biology has great potential for the heterologous production of natural products.

Starting with pathways known in specific organisms, re-cloning, codon optimization (for the

new host), and generation of gene variants to optimize activity becomes a reality with access to synthetic DNA.


Nonetheless, advances in synthetic biology tools make drug discoveries more accurate and

affordable, like never before. Better tools for understanding the basic biology behind complex

diseases need to be developed. These tools will enable researchers to identify new and

promising potential drug treatments. A partnership between academic labs and biotech firms is necessary to establish disease-specific research tools and translate basic science into

treatments and cures.

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