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Synthetic biology: A new era of possibilities

“Could we engineer living organisms and systems be engineered effectively to suit our human needs?” A question that may have met its answer in recent years.


Being predicted to reach a global value of $14 billion in 2026, the field of synthetic biology is relatively new but has been no stranger to innovative ideas since the dawn of its creation. Applying principles of engineering, mathematical modeling, computer science, and many more seemingly unrelated fields, synthetic biologists seek to build and design new biological systems that are of use to humans. 


Synthetic genomics


Perhaps one of the largest advancements in the field of synthetic biology is that of synthetic genomics. In simple terms, our DNA is composed of a different combination of 4 “alphabetic codes”. When DNA is transcribed into mRNA (a process necessary to produce proteins), the mRNA is read in triplets, called codons (Minchin and Lodge, 2019). 


Figure 1: DNA and mRNA structure. Image taken from Vedantu.


In 2013, a team from Yale and Harvard demonstrated the recoding of bacterial genome using site-specific mutation. The researchers made 321 point mutations in the sequence of natural E. coli genome. Since there is redundancy in the genetic code, these point mutations did not change the amino acid that was being coded for. This organism differed from almost all life in that it only used 63 codons instead of 64 in normal organisms (Lajoie et al., 2013). 


Figure 2: Process of reassigning a stop codon into a sense codon. Image taken from “Genomically Recoded Organisms Expand Biological Functions” (Lajoie et al., 2013).


In 2019, a study from Cambridge further reduced the number of codons used in an organism to just 61. This paved the way for using the ‘spare’ codon to add a synthetic amino acid to proteins. In February 2019, a team partly funded by NASA created an organism that had four additional synthetic “alphabetic codes” in its genome (Fry, 2019). With the additional “alphabetic codes”, the density of information that can be stored in DNA is increased. It also provided insight into what alternate systems for life might exist on other planets.


Applications in healthcare


In healthcare, synthetic biology can be used to improve diagnosis and make new treatments. Traditional medications usually have side effects due to their lack of selectivity: they bind to lots of different effectors in the body, despite only some of them being needed for their therapeutic properties (Due, 2023). Synthetic biology can be used to make treatments that are more specific and cause fewer negative effects.


Almost 50% of modern medications are naturally made by plants, including painkillers, morphine from poppies, and salicylic acid (a precursor to aspirin) from willow bark. Synthetic biology plays a role here by enabling high-efficiency production of these compounds. Yeast can be engineered to produce medicines more efficiently, on a large scale, making them more cost-effective (Garner, 2021). Perhaps the most famous application of this is the production of insulin. Before insulin was produced synthetically, it was extracted from cattle or pigs. Though it saved many diabetics’ lives, it also caused many allergic reactions and had a potency variation of up to 25% between batches. The first genetically engineered, synthetic “human” insulin was produced in 1978 using E. coli bacteria to produce the insulin. The general principle was to isolate the human gene that produced insulin, and “import” it into E. coli, hijacking their cellular machinery to produce insulin. Eli Lilly went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin (Quianzon and Cheikh, 2012).


Figure 3: Process of producing human recombinant insulin. Image taken from Toppr.


The first therapy using engineered living cells to be approved by the FDA was for treating B-cell acute lymphoblastic leukemia (ALL), a cancer affecting the antibodies-producing cells of our bodies. CD19 is a protein that is expressed in B-cells, but much more highly expressed in malignant B-cells. The treatment isolates the patient’s T-cells, another class of immune cells, and genetically modifies them to produce a chimeric antigen receptor (CAR). CAR is a fusion protein that includes an antibody that acts as a sort of receptor for CD19. The modified CAR-T-cells are then reintroduced into the patient to hunt down malignant B-cells. Not only that, CAR-T-cells can remain in circulation and continue to multiply to prevent future malignancies (FDA, 2018). Since the first approval in 2017, few other CAR-T cell therapies have been approved for B-cell malignancy targeting the B-cell maturation antigen (Chen, Abila and Mostafa Kamel, 2023).


Figure 4: CAR-T cell structure and function. Image taken from BPS Bioscience.


CRISPR is a recent addition in the toolbox that researchers have been using to selectively edit genomes. It has played a large part in synthetic biology by allowing researchers to snip, and replace specific genetic information with high precision (Amitai and Sorek, 2016). Just last month, the first CRISPR-based therapeutic has been approved by the FDA for treating sickle cell anemia. Sickle cell anemia involves a mutation in the gene coding for hemoglobin. The defective hemoglobin alters the shape of red blood cells into a sickle shape under deoxygenated conditions. This causes the red blood cells to stick together, affecting blood flow and potentially causing life-threatening clots. The treatment prevents the expression of a gene that normally prevents the body from making a form of hemoglobin found only in fetuses. The patient’s bone marrow stem cells will be removed, edited with CRISPR, and then reinfused, while destroying the untreated bone marrow. As a result, the new bone marrow produces red blood cells with a normal round shape (FDA, 2023).


Figure 5: Difference between normal red blood cells and red blood cells of those with sickle cell anemia. Image taken from National Heart, Lung, and Blood Institute.


Besides using the patient’s body cells, researchers have also been able to repurpose the symbiotic bacteria living in our bodies. Phenylketonuria (PKU) is a rare genetic disease that causes patients to be unable to break down the amino acid phenylalanine. The build-up of phenylalanine causes damage to tissues, especially the nervous system (Stone, Hajira Basit and Los, 2019). Currently, there are no treatments for PKU, and patients are only advised to eat low-protein diets to prevent exposure to phenylalanine. The pharmaceutical company Synlogic has engineered E. coli Nissle 1917 strain into a drug. It is an oral, non systemically-absorbed E. coli strain that expresses the phenylalanine ammonia-lyase enzyme to help break down phenylalanine into non-toxic molecules in the digestive tract. The drug is currently ongoing phase 3 clinical trials (Munilakshmi, 2023).


Figure 6: Mechanism of action of Synlogic’s engineered E. coli to treat PKU. Image taken from Synlogic.


Conclusion


Although currently, synthetic biology has applications beyond healthcare, such as in industrial processes, and improving the environment, the field still has untapped potential. The sort of useful things that synthetic biology strives to make are far-reaching, and it has been said that by 2030, each one of us will have eaten, worn, used, or been treated with a product made using synthetic biology. Therefore, it is important that we support those involved in the field in hopes that our future will be as bright as it can be.

 

Article prepared by: Jared Ong Kang Jie, R&D Director of MBIOS 2023/2024


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References


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