Can scientists code with DNA and create new proteins that don’t exist in nature?

Have you ever walked around the fish tanks at your local pet store and seen colorful, fluorescent fish swimming around? If you’ve visited The Tech Interactive, you may have even seen them on the second floor! 

These fish were created through a method called recombinant DNA technology. Once the subject of many sci-fi movies of the past, “coding with DNA” is now routinely used by scientists today to produce lifesaving medicines, conduct biomedical research, and develop sustainable crops.

What is DNA?

But first, what exactly is DNA? DNA is found within our cells and can be thought of as a genetic instruction manual that determines our physical traits. DNA is composed of a code of 4 different “bases”, which can be represented by the letters, “A”, “T”, “G”, and “C”. Even though there are only 4 bases, they can be combined in long sequences to form genes. Within the 3.2 billion bases that make up the human genome are all of the genes that make you, you.¹

DNA determines all our characteristics from eye color to whether or not we are lactose intolerant. This DNA instruction manual gets read by our cells to create another form of genetic material, RNA, which then gets translated into proteins. 

How exactly do scientists code with DNA?

DNA sequences can be combined in different ways, like building blocks. Imagine that you had a piece of human DNA that contained the instructions to make insulin, and a piece of bacterial DNA with the instructions for self-replication. If you put the pieces together and stick it back into a bacterium, you’ll end up with a colony of self-replicating bacteria that make human insulin!² In fact, this method is how insulin is made commercially and has been a gamechanger for those living with Type I diabetes. 

What tools do scientists use to code with DNA? One exciting and recently developed method is CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene editing, for which the 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna. 

You can think of CRISPR gene editing as using a pair of molecular scissors within a cell to make a cut in a DNA sequence at any site that you choose. Once the cut is made, a new piece of DNA can be put into the open site. The ability to use CRISPR gene editing in living cells to target specific genes has made it a valuable tool that is currently being investigated to treat diseases like sickle cell anemia and cancer.

Can we create new proteins that haven’t previously existed in nature?

What scientists have done for many years now is make changes to existing DNA sequences to create slightly different versions of naturally occurring proteins. Let’s go back to the GloFish in the fish tank on the second floor of The Tech Interactive. How exactly were they created? 

In the 1990s, scientists wondered if the fluorescent protein made by bioluminescent jellyfish could be produced in other organisms as well. The gene with the instructions for making the jellyfish’s “green fluorescent protein” (GFP) was sequenced and put into bacteria. The bacteria then began to make GFP and glow green!³

Since then, GFP and other fluorescent proteins have made their way into research. Cells and proteins are extremely small and seeing what they are doing within an organism is tricky. By combining the DNA sequence for fluorescent proteins with other sequences (similar to how the insulin-producing bacteria were made), scientists can make cells and proteins glow, making them much more easily studied.

Over the years, scientists have made tweaks to these fluorescent proteins to create new colors and to make them brighter and more stable.⁴ The colorful GloFish in the fish tanks produce these modified versions of GFP and other fluorescent proteins within their muscles.⁵

In contrast to modifying existing proteins, designing completely new ones from scratch that achieve a desired function is much more complicated. Proteins have a highly precise and complex structure – even slight changes can lead to a protein that doesn’t work anymore. This is why mutations to our DNA, even a change in just a single base, can have dramatic effects and lead to genetic disorders. Recently however, technological advances in computing and artificial intelligence are enabling scientists to do just that. 

By training software on databases of different protein structures, scientists at the University of Washington have developed machine learning tools to generate new proteins with desired functions. For instance, the software was able to create a new protein designed to interact with a different protein found on the surface of certain cancer cells. The key lies in prompting the software with a desired protein structure as a starting material that the software can then build onto to form a complete protein, similar to the autocomplete feature you’d find when texting on your cellphone.

What about creating new genes?

Another recently developed machine learning tool is Evo 2.⁶ Evo 2 is trained on a massive database of DNA sequences from all living (and even some extinct) species. 

Similar to the approach of autocompleting a protein, Evo 2 can be given a starting DNA sequence, and it can build on it to create a never before seen gene! In nature, new genes show up as a result of evolution over many millions of years, while Evo 2 artificially accelerates this process to a much shorter timescale, a truly remarkable feat made possible by the intersection of biology and computing. 

Scientists can then create these genes and test their functions in the lab, to make fundamental discoveries and to find new and effective treatments for diseases. With all of these new technologies at our disposal, it’s an exciting time to be in science!