CRISPR Goes Back to Its Microbial Roots

In my studio this morning, surrounded by half-finished illustrations and coffee rings on my drafting table, I found myself deep in research about one of the most fascinating scientific developments of our time. CRISPR technology has captured headlines for years with its potential to edit human genes, but what’s truly captivating is how this revolutionary tool is circling back to its origins—the microbial world.

The human body is a walking ecosystem. Billions of bacteria, fungi, and other microbes inhabit our bodies, forming what scientists call our microbiome. These microscopic communities are not mere passengers; they’re active participants in our biological processes, helping with digestion, immunity, and countless other functions. When these microbes live harmoniously with our cells, everything runs smoothly. But when the balance tips, conditions from Crohn’s disease to persistent acne can emerge.

This delicate balance presents both challenge and opportunity for medical researchers. Rather than editing human cells, some scientists are now turning CRISPR’s precise genome-editing capabilities toward the microbes themselves.

“It is ironic that even though genome editing tools like CRISPR-Cas9 were invented by bacteria, they’ve been used most efficiently in mammalian cells,” notes Peter Turnbaugh, a microbiologist at the University of California, San Francisco. “They haven’t had the same kind of transformative effect on bacterial genetics as they have on human genetics.”

Crispr – The Delivery Challenge

The concept sounds straightforward: use CRISPR to edit problematic microbes without harming beneficial ones. But implementation faces significant hurdles. How do you deliver genome-editing machinery to bacteria tucked away in intestinal folds or beneath layers of mucus?

This reminds me of an illustration project I worked on for a children’s science book last year—trying to visualize microscopic delivery systems was like drawing invisible messengers carrying molecular mail! The challenge of depicting something so tiny yet so complex pushed my creative boundaries in ways I never expected.

Companies like France-based Eligo Bioscience are tackling this delivery challenge by drawing inspiration from nature’s own microbial hunters: bacteriophages, or phages for short. These specialized viruses that infect bacteria might hold the key to targeted microbiome editing.

Crispr - bacteriophage attaching to bacteria

Phages are nature’s precision instruments. Resembling tiny lunar landers with angular legs and geometric heads, they attach to specific bacterial strains and inject their genetic material inside. Some estimates suggest phages outnumber bacteria by a factor of ten, making them what Bryan Hsu, a microbiologist at Virginia Tech, calls “the dark matter of the gut microbiome.”

This specificity makes phages potentially perfect delivery vehicles for CRISPR systems. Unlike broad-spectrum antibiotics that indiscriminately wipe out beneficial bacteria along with harmful ones, phage-delivered CRISPR could precisely target problematic microbes while leaving beneficial populations intact.

Crispr – Beyond Killing: Modifying Instead of Destroying

Traditional phage therapies aim to kill bacteria, but this approach has limitations. As Hsu explains, “You have such a competitive environment in the gut microbiome that other bacteria would love to take their place.” Or worse, surviving bacteria might develop resistance to the phage—similar to antibiotic resistance.

The promise of CRISPR-based approaches lies in their ability to modify rather than destroy. If a microbe is producing a disease-causing molecule, CRISPR-Cas9 could precisely disable that specific gene without killing the entire bacterial population.

I’ve always been fascinated by this idea of selective editing rather than wholesale destruction. It reminds me of my own artistic process—sometimes the perfect illustration doesn’t need a complete redraw, just careful adjustment of certain elements. The precision of CRISPR seems to mirror the careful hand of an artist making targeted improvements to their work.

Overcoming Technical Hurdles

Adapting CRISPR for bacterial editing presents several technical challenges. Bacterial cells react differently to DNA cuts than human cells do—they’re particularly sensitive to double-stranded breaks. This means researchers must ensure that DNA editing doesn’t trigger cell death, defeating the purpose of the precise approach.

Another hurdle is that bacteria have evolved defenses against phages, including systems that can recognize and destroy foreign DNA. The irony isn’t lost on scientists: they’re essentially trying to use systems derived from bacterial defense mechanisms to overcome those very same defenses.

Turnbaugh’s research has shown that bacteria can evolve to escape genome editing strategies, presenting yet another challenge. Nature has been playing this evolutionary chess game for billions of years, and bacteria are grandmasters at adaptation.

From Lab to Therapy

Despite these challenges, progress is being made. The FDA approved the first gut microbiome-based drug, SER-109, in 2023. While not a CRISPR-based treatment, this pill containing beneficial bacteria to fight C. difficile infections represents an important step toward microbiome-targeted therapies.

Several companies are working on CRISPR-based approaches. Eligo Bioscience has developed what they call “eligobiotics”—engineered phages that deliver CRISPR systems to target specific bacterial genes. Another company, Locus Biosciences, is combining phage therapy with CRISPR to develop treatments for antibiotic-resistant infections.

The potential applications extend beyond infectious diseases. Research suggests that microbiome imbalances may contribute to conditions ranging from inflammatory bowel disease to certain neurological disorders and even cancer. Precise microbiome editing could offer new treatment avenues for these conditions.

Crispr - scientist working with microbiome samples

Ethical Considerations and Future Directions

As with any powerful technology, microbiome editing raises important questions. Our understanding of the microbiome remains incomplete—we’re still cataloging which microbes live where and what they do. Altering these complex microbial communities could have unforeseen consequences.

There’s also the question of persistence. Unlike human genome editing, which creates permanent changes that can be passed to future generations, microbiome edits may be temporary as new microbes colonize the body. This could be viewed as either a limitation or a safety feature, depending on the context.

One thing that keeps me awake at night when I think about illustrating these concepts is how to visually represent the ethical dimensions of microbiome editing. How do you draw a moral dilemma? It’s something I’ve been sketching ideas for in my personal work—perhaps showing the microbiome as a delicate mobile with interconnected pieces, where touching one element causes the entire structure to shift.

Looking ahead, researchers envision personalized microbiome medicine. Just as each person’s genome is unique, so too is their microbiome. Future treatments might be tailored to an individual’s specific microbial profile, targeting problematic strains while preserving beneficial ones.

The journey of CRISPR from bacterial defense mechanism to human gene editor and now back to bacterial modifier illustrates a fascinating scientific circle. By returning these tools to their microbial roots, researchers hope to develop therapies that work with our body’s natural systems rather than against them.

The microbiome represents a frontier in human health—a complex ecosystem within us that we’re only beginning to understand and influence. As CRISPR technology evolves to edit these microscopic communities with increasing precision, we may find ourselves with powerful new ways to restore balance to the body’s invisible landscape, treating disease by healing our relationship with the microbial world we carry with us everywhere.