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A step towards a world where semisynthetic life form is healthy and can replicate?

by Dr Heather Doran

The four bases of DNA write the script for all the proteins that create life but a limited alphabet rescricts language and its possible forms and functions. In 2014 scientists were able to add two new synthetic letters of code to the genetic alphabet and proved they were viable. Now they have made a significant advancement to prove that synthetic DNA can not only be created and integrated into a single celled organism but that the resulting semisynthetic life form is healthy and can replicate.

The four DNA bases pair together, A-T and C-G to create the famous double helix structure and conserve the code for everything from bacteria and bananas to horses and humans. Back in 2014 researchers at The Scripps Research Institute, La Jolla California successfully engineered two new letters of DNA code, a new base pair, and integrated them into a bacterium, creating the very first semisynthetic life. Although they proved that a semisynthetic organism is possible the bacteria wasn’t stable and had many limitations.

Two of the fundamental characteristics of life is the ability to grow and to reproduce. The researchers needed the semisynthetic bacteria to grow and replicate while continuing to keep the new DNA code and passing it from parent bacteria to offspring. They found, that although the bacteria could incorporate the artificial DNA, it was eventually lost from the organism. The semisynthetic life form also grew more slowly than its original form. However, in early 2017 the same group revealed they had overcome these issues, creating the next stage of semisynthetic organism healthier and more viable than the first.

In order to achieve this updated version of semisynthetic life, the team edited the make-up and structure of the synthetic base pair to make it more stable and altered how it was delivered into the bacteria. They also created an inbuilt quality control using the DNA editing tool CRISPR-Cas9 to make sure the organism retained the new DNA base pair over time when replicating.

Although this research may seem like a step towards a world where any organism can be created with new features, this study in a single-celled organism and the research is not destined for more complex living bodies. But there are still huge potential implications of this development, for one it moves us a step closer to the fundamental question of understanding how life itself evolved. The main drivers of this research though are that it may be the key to developing a range of new drug treatments. Many drugs today are already created in biological systems like bacteria and fungi, known as biopharmaceuticals, then they are extracted for use. The design of these drugs and their structure is limited by the current four-letter genetic code, the ability to create new letters of code and the expansion of the genetic alphabet may have the potential to create biologically synthesised drugs with a range of new structures and functions.

Photo credits: Professor Floyd Romesberg (right) and Graduate Student Yorke Zhang led the new study at The Scripps Research Institute, along with Brian Lamb (not pictured).(Photo by Madeline McCurry-Schmidt.) 

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