By Alissa Bray
When we think about key events in the history of Genetics and Molecular biology, we often think of the discovery of the three-dimensional structure of DNA.
However, that was only a small step on a path that humans have been walking for thousands of years. Genetic modification has been exploited for gain since the domestication of dogs over 14,000 years ago.
Today, we utilise a deeper understanding of the building blocks of life to bend DNA to our will. From simple plasmid DNA engineering to complex genome editing, molecular biology is allowing us to unshackle progress, and develop novel therapies which will change the face of modern medicine.
The History of Genetics
One of the earliest experiments to uncover the nature of DNA was conducted in 1865 by Gregor Mendel, who crossed pea plants to show that characteristics were inheritable.
Crossing tall and short plants never resulted in medium-height plants, as only either “tall” or “short” was the information which could be passed on to future generations. Mendel’s work, however, went largely ignored at the time.
In 1926, genes were purposefully mutated by Hermann Joseph Muller using x-rays, and then the “transforming principle” was demonstrated less than two years later, in 1928, by Frederick Griffith.
He used two strains of bacteria, one with a rough coat which is destroyed by the mouse immune system, and one with a smooth coat which is not.
Mice injected with rough bacteria lived, but those injected with the smooth-coated bacteria died. If the smooth bacteria were heat-killed prior to injection, the mice lived. However, upon injection of mixed heat-killed smooth bacteria and live rough bacteria, the mice died.
Something had passed from the dead smooth bacteria to the live rough bacteria, rendering the rough bacteria lethal. This transforming principle was shown to be DNA - not protein - by Avery, McLeod and McCarty in 1944.
Then in the summer of 1951, James Watson and Francis Crick set out to discover the three-dimensional configuration of the gene.
Using high-resolution x-ray images of DNA fibres obtained by Maurice Wilkins and Rosalind Franklin, and the findings by Erwin Chargaff that bases adenine and thymine, and guanine and cytosine, occurred at ratios of one-to-one respectively, Watson and Crick deduced the now iconic double-helical structure of DNA.
This pivotal moment in molecular biology led to the Nobel Prize in Physiology or Medicine for Watson, Crick, and Wilkins, and triggered an exponential surge in genetic engineering.
The Plasmid Revolution
Knowledge of the structure of DNA allowed more targeted engineering of DNA. From the discovery of bacterial plasmids in 1952, ligases in 1967, and restriction enzymes in 1970, Herbert Boyer and Stanley Cohen pioneered recombinant-DNA technology – now a mainstay in every molecular biology laboratory.
Modifying plasmids has allowed enormous possibilities for research and medicine. In 1979, the human insulin gene was placed on a plasmid and used to make recombinant E. coli, from which insulin could be harvested.
This revolutionised the treatment of Type 1 diabetes and abolished the need to harvest bovine or porcine insulin from pigs and cows.
In 2011, plasmids became the foundation upon which Oxford Genetics was conceived. Initially utilising the modular SnapFastTM system to revolutionise DNA design and production, it then progressed to using those engineered plasmids to underpin the development of novel technologies.
In Gene Therapy, Oxford Genetics developed plasmid systems to improve the yield of both recombinant Lentivirus and Adeno-associated Virus (AAV).
Subsequently, it used these viral vectors to design and create unique viral packaging and producer cell lines, tackling major challenges that have made many gene therapy treatments prohibitively expensive.
One of the biggest discoveries in genetic engineering of the past decade has been CRISPR-Cas9. Put simply, it uses targeted molecular scissors that can cut DNA and edits the genome directly.
It was in 2012 that Jennifer Doudna and Emmanuelle Charpentier showed it could be used to target and cut a pre-determined DNA sequence. Genetic engineering became genome editing.
Although often masked by media coverage of ethical debates and designer babies, CRISPR-Cas9 has emerged as a low cost, simple and versatile way to accelerate research and development for virtually all areas of medicine and synthetic biology.
It has become theoretically possible to genetically remove diseases from our DNA.
Oxford Genetics has combined its proprietary SnapFastTM modular DNA system with high throughput automated genomic engineering platforms for CRISPR-Cas9 modification of cell lines, allowing it to generate hundreds of custom-engineered cell lines for use in research and therapeutic development.
In a rapidly expanding field, Oxford Genetics has the technology to meet the need for large numbers of these custom cell lines to further global research and development.
With the advent of CRISPR-Cas9 gene editing we can modify any organism which contains DNA in any way we see fit. We are headed towards a world of unlimited possibilities.
Wielded correctly, genetic engineering is a tool which can enable truly personalised medicine and advances in medical research.
It is a tool that Oxford Genetics is wielding to push the frontiers of modern biotechnology and medicine, unimagined by those hunter-gatherers over 14,000 years ago.