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.
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.
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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