This article is a guest post by Aurelija Grigonyte, a synthetic biology PhD student, currently working on phage therapies.
Imagine a world where your disease is immediately treated with a drug, designed uniquely for you, making it incredibly efficient. Even better, imagine a technology which, after inputting the parameters of your body, outputs a prediction and hence prevents a future illness. This is the dream of personalised medicine.
What is Personalised Medicine?
Personalised medicine (PM)1,2 tailors a given therapeutics towards an individual, using personal biological data outputs such as genomics, transcriptomics, pharmocometabolic information, and environmental as well as circumstantial factors. PM may also be referred to as a distant relative of evidence-based medicine, which relies on research done on a number of different individuals and uses the evidence collected to standardise the treatment for a particular disorder.
PM has a long way to go to fulfil its potential; however, the synbio toolbox has accelerated the journey.
What can Synthetic Biology offer Personalised Medicine?
Synbio, or the engineering of biological systems, not only allows the construction of new biological entities e.g. cells and genetic interactions, but also builds on our understanding of disease mechanisms. This in return generates cheaper alternatives to existing therapies and allows novel treatments in multiple specialities, such as metabolic disorders and cancer.
The synbio bottom-up approach is particularly relevant to PM as it advocates the understanding of individual genes, molecules, networks and translates these into an overall output for the systems of the human body.
Cell Therapy and Synbio
Cell therapy is one of the earlier forms of PM. Here, the treatment is cells either directly obtained from the patient or newly synthesised, which are injected into the patient. Embryonic stem cells, as well as subtypes of somatic cells, can be modified to fit the treatment. In the case of stem cells, they can be programmed to differentiate into a particular specialised cell type e.g. cardiomyocytes, by controlling gene expression and inserting specific sequences, as well as the 3D microenvironment. This can later be employed for cancer therapy as well as tissue regeneration.
Already differentiated somatic skin or blood cells can be reverted back to stem cells and then used to obtain a particular somatic cell type. These induced pluripotent stem cells (iPSCs) are regenerated by direct administration of pluripotency-activating mRNAs which circumvents the integration of genes into their genomes. These mRNAs are then translated into proteins, completing the cells’ transformation to stem cells. These newly generated stem cells can then be further differentiated using the mRNA strategy to fit the needs of research or a treatment in question.
Gene Therapy and Synbio
Gene replacement by transgenesis is a core technology for the gene therapy. In transgenesis, a faulty gene is compensated for by having a correct version of the gene placed inside the cell alongside the faulty one. The transgene control systems treat single-gene defects by triggering an expression of a complementary transgene. For instance, it has also been shown that transgenes can evoke cancer cell destruction by pre-programed bacteria.
One of the most recent gene therapy technologies by direct gene editing is CRISPR. “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are an essential part of the bacterial defence system and which has been hijacked by synthetic biologists and employed as genome editing tools. CRISPR allows for permanent and specific genetic code targeting and editing in living organisms. More recently, this technology has been used for human embryonic gene editing.
In 2017, a team of researchers used CRISPR–Cas9 gene editing to fix a disease-causing dominant mutation in numerous of viable human embryos. The study targeted a gene that, when faulty, causes a condition known as hypertrophic cardiomyopathy, which manifests as thickened heart muscle. The faulty gene editing was performed on sperm cells prior to in vitro fertilisation. The resulting high rate of embryos containing the fixed gene was a great accomplishment, allowing us a sneak peek into the potential of CRISPR technology in a clinical setting.
Synbio’s role in the Future of Personalised Medicine
Exciting and informative synbio projects are underway to shed even greater light on its application possibilities. An example of the most recent big-scale endeavour is the Genome Project–write (GP-write) which aims to build, among others, a synthetic human genome from scratch to uncover even greater complexities of our genes, their functions and disease mechanisms. It is an endeavour to improve basic science by reducing the costs and advancing the technology of synthesis of large genomes, as well as by learning more about the structure of the genome and how specific elements (such as non-coding regions) work. In a nutshell, HGP-write aims to do for DNA synthesis what the Human Genome Project (HGP-read) did for the advancement of sequencing.
There is no doubt that the role of synbio in PM is going to grow in the future. It will not only contribute to the advancement of existing therapies but also to the development of new methods for disease detection, making preventative medicine a core part of PM.