Infographic showing some of the many applications of genome editing covered in this post. These include: basic research (breaking DNA sequences encoding cellular parts to learn their functions), therapeutic genome editing (in vivo genome editing and cell therapy), and bio production (engineering cells to produce useful compounds).

Many of the tools in the ever-expanding CRISPR toolkit are lauded for their genome editing capabilities. That is, these tools make it easy for scientists to change specific DNA sequences in precise ways. Yet, what truly makes these tools exciting is their fascinating applications. In this post we’ll cover just a few of the many exciting applications of genome editing:

  • Basic research – discovering the functions of cellular parts
  • Therapeutic genome editing – using genome editing to fight disease
  • Bioproduction – making cells better at producing useful compounds

Basic research – discovering the functions of cellular parts

Biology is complicated. Cells interact with one another in complex ways and they are composed of many parts that interact with one another as well. As such, there is still a ton we don’t know about how cells and organisms work. We understand the basics – that DNA contains the instructions for producing cellular parts. Yet, we don’t know what many of these cellular parts do.

Genome editing enables us to get a better understanding of cellular parts and their functions. Indeed, one of the most important ways we can use genome editing is to break the DNA sequences encoding cellular parts. By breaking these DNA sequences, we cause the parts they encode to malfunction. We can then see what effect these malfunctioning parts have. In-so-doing, we can associate cellular parts with particular functions. This is like removing an ingredient from a recipe and seeing how it changes the final meal.

In the past it took a long time to break DNA in targeted ways. Indeed, even if we had a relatively good technique for one kind of cell or organism, there was no guarantee that it would work in another kind of cell or organism. Thus, we might have to develop new DNA altering techniques for different organisms and experiments.

Thankfully, CRISPR genome editing tools work well in many types of cells. Although CRISPR systems come from bacteria and have been optimized for use in human cells, they are being used in many organisms to learn more about their biology. 

CRISPR genome editing in action: Learning how mosquitoes detect heat

For example, researchers recently used CRISPR genome editing to study the function of a particular cellular part found in mosquito antennae. The part is called IR21a. The researchers thought IR21a might help attract mosquitoes to heat. They hypothesized that, with the aid of IR21a, mosquitos home in on warm, blood-filled bodies. 

To determine if this is the case, the researchers used CRISPR genome editing tools to break the DNA encoding IR21a. Among other things, the researchers found that mosquitos with broken IR21a DNA were less likely than un-altered mosquitoes to land on warm patches in their cages. Their antennae cells were also less responsive to changes in temperature than those in un-altered mosquitoes. Thus, CRISPR genome editing experiments gave these researchers good evidence that IR21a is involved in heat attraction.

This is just one example of the many, many ways that genome editing and, in particular, CRISPR genome editing tools are used in basic biology research. For examples in human biology, see this report from the National Academies of Sciences, Engineering, and Medicine. With CRISPR’s help, we’re rapidly getting a better understanding of many biological phenomena.

Therapeutic genome editing

There are many human ailments that can be treated using genome editing. Researchers conceptually break down these therapies into two broad groups:

In vivo genome editing – Here genome editing tools repair broken DNA sequences in cells in the body.

For example, there is an up-and-coming therapy using CRISPR genome editing to treat a form of inherited blindness. This requires the injection of CRISPR tools into the eye. The tools then enter retinal cells and make targeted changes to photoreceptor cell DNA. These changes will hopefully help restore vision.

Cell therapy – Here genome editing tools edit cells outside the body. Researchers then deliver the edited cells to the body where they have their therapeutic effects.

A great example of cell therapy is CAR-T cell therapy. In this exciting new type of therapy, researchers give T-cells a new cellular part called a CAR. The edited cells are known as CAR-T cells. CARs enable T-cells to target and destroy other kinds of cells in the body. Often, CAR-T cells destroy cancer cells. Indeed, researchers recently used CRISPR tools to create CAR-T cells that attack aggressive cancer cells. A phase I clinical trial showed that these CAR-T cells are safe to use in patients.

For an in-depth discussion of therapeutic genome editing, see the “Somatic Genome Editing” chapter of this report from the National Academies of Sciences, Engineering, and Medicine.

Genome editing for bioproduction in mammalian cell factories

Companies produce many pharmaceutical products in mammalian cells. These cells are grown under specific conditions in specialized bioreactors. Some of the pharmaceutical products produced in mammalian cells include:

  • Therapeutic antibodies 
  • Hormones
  • Blood proteins

Indeed, many of these compounds would be difficult to create using strictly chemical means. Cells, however, have the requisite enzymes to make production relatively easy. They are like tiny cell factories.

Unfortunately, cells aren’t naturally very good at producing useful compounds in large amounts. It can take many years of modifying growth conditions, genetic engineering, and directed evolution to make cells particularly good producers. Companies have had much success making better and better cell factories (see review here). However, many of the processes classically used to make better cell factories are slow and far from perfect. In addition, researchers must often modify their processes and cells whenever they wish to produce a new compound.

Genome editing tools make it much easier to modify cells used for bioproduction processes. For example, mammalian cells contain a whole slew of enzymes that modify therapeutic proteins by adding new chemical groups to them. These chemical groups may also decrease a protein’s therapeutic potential. To solve this problem, researchers can use genome editing tools to break the genes encoding these detrimental enzymes. Thus, researchers can improve the therapeutic properties of the proteins produced in their cell factories.

Genome editing tools also help ensure that cell factories effectively synthesize therapeutic compounds from the genes that encode them. To produce such compounds, researchers often introduce new genes into cells. Classic methods for doing so inserted these genes at random sites in the genome. As a result, the proteins encoded in these genes would be produced in different amounts in different cells. Researchers would spend a lot of time finding cells that produced these proteins in the proper amounts. With CRISPR genome editing tools, it’s possible to direct gene insertion at precise locations. This reliably results in a useful amount of production.

With the many benefits of genome editing in the creation of mammalian cell factories, we’ll hopefully see many more useful compounds produced in cells in the future. This may lead to downstream benefits like lower therapeutic costs and increased availability!

Many, many more applications of genome editing

These are just some of the many applications of genome editing. For example, you can learn about some of the applications of genome editing in crops here. Importantly, CRISPR tools make it much easier to achieve genome editing’s applications. CRISPR tools will greatly accelerate the pace at which these applications have impacts both in and out of the lab. As new CRISPR systems are discovered, they’ll accelerate the development of these applications even further. We’re incredibly excited to be at the forefront of this pivotal time in biotechnology!