Using CRISPR To Reverse Antibiotic Resistance

The Rise Of Antibiotic Resistance

Bacterial infections are much less deadly than they used to be before the introduction of antibiotics.

“Before we had antibiotics, infections like scarlet fever could even lead to heart problems. Surgery often led to deadly infections in the blood, like bacteremia or septicemia.

A World Without Antibiotics

Because antibiotics silently save so many lives every day, we have started to take them for granted. But this is far from a safe assumption. Bacteria evolve very quickly, and not dying from antibiotics is a strong evolutionary pressure. So, it is common for a new antibiotic to lose its efficiency after 10-15 years.

The only thing that kept antibiotics ahead of bacterial resistance was the effort of researchers to keep finding new molecules decade after decade. This is a silent war between researchers and pathogens.

Recently, pathogens started to win. Antibiotic resistance is a growing problem, especially concerning diseases contracted in hospitals. Antibiotic resistance kills more than 1.27 million people yearly worldwide. Very few new antibiotic classes have been discovered since 2000.

Source: Aphage

Worth, the omnipresent micro and nanoplastics were discovered to reduce antibiotic efficiency. Some newer approaches could help, like antibacterial polymers, mRNA vaccines, or living antibiotics called phages.

All these new ideas will help, but none of them removes the problem that bacteria keep adapting to new antibiotics and antibacterial methods quickly.

Another concept has just been discovered by researchers at the University of California, which “contaminates” bacterial populations so they lose their antibiotic resistance, leveraging the CRISPR gene editing system.

They published their results in a study¹ titled “A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population”.

Making CRISPR Into An Antibiotic

A Long-Term Effort

The scientists developed in 2019 a CRISPR-based tool called Prokaryotic-Active Genetics (Pro-AG).

It disrupts the genes encoding for antibiotic resistance factors carried on a plasmid (a piece of circular DNA common in bacteria) by the precise insertion in the targeted genes, deactivating them. This approach proved promising, as it outperforms standard cut-and-destroy CRISPR anti-antibiotic resistance approaches by over 100-fold.

The team developed a second-generation Pro-Active Genetics (Pro-AG) system called pPro-MobV.

Source: Antimicrobials & Resistance

This updated technology is designed not just to remove antibiotic resistance, but also to spread through bacterial communities and disable the genes that make them resistant to antibiotics.

It did so by weaponizing against the bacteria “conjugal transfer”, a process similar to bacterial mating, that normally plays a key role in spreading genes causing resistance to antibiotics. Here, it instead spread the vulnerability to the antibiotics.

Self-Spreading Antibiotic Sensitivity

The idea is similar to other population control deployed in insects, with, for example, populations of malaria-carrying mosquitoes “contaminated” with lab-made variants that cannot carry the disease, spreading the trait when they reproduce.

“With pPro-MobV we have brought gene-drive thinking from insects to bacteria as a population engineering tool. With this new CRISPR-based technology we can take a few cells and let them go to neutralize AR in a large target population.”

Professors Ethan Bier – UC San Diego School of Biological Sciences

This method created a ~1000-fold reduction in bacterial spread in a lab test.

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More importantly, it also works on biofilms, a dense network of bacteria that cling to surfaces and make them insensitive to antibiotics and disinfectants. Biofilms are involved in the most serious infections by forming a protective barrier that limits how easily drugs can penetrate.

“The biofilm context for combating antibiotic resistance is particularly important since this is one of the most challenging forms of bacterial growth to overcome in the clinic or in enclosed environments such as aquafarm ponds and sewage treatment plants.”

Professors Ethan Bier – UC San Diego School of Biological Sciences

Being able to impact biofilms in sewage plants and farms could also radically reduce the spread of antibiotic resistance to people.

“If you could reduce the spread from animals to humans you could have a significant impact on the antibiotic resistance problem since roughly half of it is estimated to come from the environment.”

Professors Ethan Bier – UC San Diego School of Biological Sciences

Pairing CRISPR With Bacteriophages

The method has so far been deployed in bacterial plasmids. But it could also be spread to bacterial populations through specialized viruses that only attack bacteria, called bacteriophages.

This could make it especially powerful to treat patients or large facilities, as the modified viruses can self-replicate and spread by themselves.

“This technology is one of the few ways that I’m aware of that can actively reverse the spread of antibiotic-resistant genes, rather than just slowing or coping with their spread.”

Justin Meyer – UC San Diego School of Biological Sciences

Conclusion

Antibiotic resistance is a growing problem, even if renewed scientific effort might find, for a while, new drugs and other antiseptic methods to keep the consequences at bay.

Thanks to modern genetic engineering, the appearance of antibiotic resistance could one day not be a fatality that hits any new treatment in a decade or so after its release.

This research illustrates the extraordinary versatility of CRISPR technology, which went from an interesting genetic mechanism to a tool for curing genetic diseases, modifying crops, and now even alleviating antibiotic resistance.

Investing In CRISPR Technology

Editas was founded by CRISPR-Cas9 co-discoverer Jennifer Doudna. Editas started working with Cas9 but is now focused on a proprietary version of Cas12a that they engineered: AsCas12a.

You can read more about Cas12a’s unique properties in our dedicated article “What Is CRISPR-Cas12a2? & Why Does It Matter?”.

Source: Editas

You can also read an overview of all of Jennifer Doudna’s companies in the corresponding article “Top Jennifer Doudna Companies to Watch.”

Editas is focused on Sickle Cell Disease (SCD) and beta-thalassemia, 2 diseases where it lost the race for first treatment approval to competitors CRISPR Therapeutics and BlueBirdBio.

Overall, the SCD program (recently renamed Reni-Cell) has been delayed several times, sparking concern among investors, and has since been refocused on in vivo therapy to distinguish it from already approved SCD therapies.

Nevertheless, Editas owns significant patents on CRISPR-Cas12, which has been used by researchers at the University of New South Wales, Australia, to develop a COVID-19 strip test, illustrating the technology’s potential beyond gene editing.

Editas also signed in 2023 a $50M deal with Vertex for the company to use Editas’ Cas9 IP.

Editas focuses on other CRISPR versions than the “classical” CRISPR-Cas9 and its research IP might come in handy in establishing partnerships and generating revenues without an FDA-approved product, on top of a cash runway going into 2026.

As Cas12a seems to become increasingly proven as a best-in-class method for multi-gene editing, Editas’ expertise and pipeline focus on this CRISPR variant might prove a winning bet in the long run.

(You can also read more about other CRISPR companies in our corresponding article “Top 5 CRISPR Companies To Invest In”.)

Latest Editas (EDIT) Stock News and Developments

Study Referenced

^{1. Kaduwal, S., Stuart, E.C., Auradkar, A. et al. A conjugal gene drive-like system efficiently suppresses antibiotic resistance in a bacterial population. NPJ. Antimicrobials & Resistance. 4, 8 (2026). https://doi.org/10.1038/s44259-026-00181-z}