What is gene editing?

2.16.20 CRISPR UPDATED.mp4 from Hybrid Performance Method on Vimeo.

What is gene editing? 

We recorded an episode of Hybrid Unlimited with genetic engineering expert, Josiah Zayner. 

We learned how gene therapy and gene editing work, and how these technologies might make their way into sports in the near future. 

Before you listen to the episode, I want you guys to make sure that you remember how genetics work. 

Alright, so the code of life is written in DNA - an unimaginably long, self-copying molecule that carries all of the information to make a living organism. 

The image of DNA as a twisting ladder or double helix, is ubiquitous from high-school biology class to science-fiction movies. This form supports its function. 

The twisting beams of the ladder are formed by sugars attached to a backbone that keeps the molecule intact as they float among other chemicals inside of the cell. 

The rungs of the DNA ladder are made of base pairs - they’re like the alphabet of DNA- they are A (adenine), T (thymine), C (cytosine), and G (guanine). 

Each base is only congruent with another base. 

The double helix structure of DNA enables both self-replication and cellular reconstruction. 

Only one side of the ladder is needed to build the other half so specialized proteins can read DNA to make copies and also to make other proteins. 

The message to make a protein is written in a language of base pairs and is carried by RNA to another part of the cell where the protein can be assembled from those instructions. 

It’s like making copies of your favorite strawberry shortcake recipe so you can keep the original stored somewhere safe. 

So by altering the composition and sequence of letters, an endlessly complex set of instructions can be built out of a simply, four letter alphabet. 

Your DNA gets transcribed by your RNA and gets translated into proteins. That is the central dogma of biology and it’s that simple. 

It gets a little more complicated when you recognize that the environment changes the behavior of proteins which comes full circle to regulate DNA. 

Over the course of a lifetime, sections of DNA are frequently turned off or on or even changed via mutations. 

Sometimes these changes are predictable, but oftentimes they’re not. Much of the genome remains constant, but a critical percentage of it changes over time and those differences reflect our differences. 

In this second section, we’re going to talk about genetic modifications. 

The two kinds of tools we focused on in the podcast are gene therapy and gene editing. 

They’re similar, but they have key differences. So I want to cover how both of these work ahead of time to clear out any confusion.

In the podcast, Josiah explains gene therapy first. This method is cheap, accessible, and transient. It simply involves saturating cells in a specific fragment of synthetic DNA that codes for a specific protein. 

All of the extra copies of the DNA should make more copies of the protein which should change the way that the cells behave which should create an observable change such as muscle growth, for example. 

This approach depends on enough intact DNA getting into the right cells and enough proteins appearing as a result. 

The second method of gene therapy is using nature to our advantage. 

Viruses survive by inserting their DNA or RNA into a host cell - hijacking its machinery. Viruses survive by doing gene therapy so that begs the question, “why not use a non-infectious virus as a vector to insert the DNA we actually want into a cell with greater specificity and efficiency?” 

Some viruses can even permanently insert DNA into a cell’s genome and among those 3 billion base pairs, some sections are layered with what seems to be an ancient viral DNA. 

Inserting genes is one thing, changing them is something else entirely. 

That's where gene editing comes in and for that we turn from viruses to bacteria. 

In the war against viruses, bacteria have put up defenses. We call one such defense system, CRISPR, or Cas9. 

It behaves like a bacterial immune system. Sections of viral DNA are stored in the CRISPR sequence after an infection. 

When the viral DNA reappears, the sequence codes a guide RNA that directs a protein called Cas9 to the viral DNA. Cas9 then cuts the DNA to deactivate it. This process can be modified to work in human cells mostly to accomplish 3 things. 

First, it could deactivate genes that we don’t want active 

Second, it could change genes by changing the base pair code. 

Third, it could add and insert an entirely new gene into the thread: combining elements of gene therapy and gene editing into one, streamlined process. 

The result? CRISPR or Cas9 is the cheapest, most effective tool of today. 

However, some of the same technical hurdles that plague other forms of gene therapy still remain. 

On top of that, we now run the risk of unintended changes and their consequences as well. 

Gene editing and gene therapy are profoundly versatile tools. They might influence anything that has to do with genes which is just about everything. 

Josiah believes genetic engineering should include cures for disease and it should be available to anyone to experience if they so choose. 

We still struggle to read and comprehend the story written in our DNA. How can we even begin to write the sequel?

Josiah thinks the answer relies on autonomy and access. 

The more people who have access to these tools and the more free they are to decide for themselves, the closer we will close the gap between us and genes. 

Do the potential benefits outweigh the risks? I don’t know, but I do think that one day we will find out. 

Now that you know the basics, you’re ready to listen to the expert on the latest episode of Hybrid Unlimited! 

If you want to learn more about genetics, Check out the show notes at blog.hybridperformancemethod.com for additional resources. 

Hope you enjoyed and I’ll catch you guys next time! 

- Stefi