CRISPR gene editing, one of the most impactful biological tools of the 21st century, famously has its origins in microbial warfare. The technology was based on enzymes that bacteria use to defend themselves against viruses. But viral invaders have a few tricks of their own, and now scientists are raiding their armory to build the next generation of gene editing technologies.

Stylus Medicine is at the forefront of renewed interest in recombinases, proteins that some viruses use to stitch their genes into bacteria. If they can be repurposed, it would give scientists a long-sought way to deftly insert entire therapeutic genes at safe spots in the human genome, something that CRISPR still struggles to do.

The company’s roots lie in Ami Bhatt’s lab at Stanford, which created a bioinformatics tool that helps spot new recombinases in a sea of microbial murk. Although other scientists have toyed with turning recombinases into genetic engineering tools, their utility has been limited because they have evolved to target bacterial DNA sequences — and unlike CRISPR, they were difficult to reprogram for use in human cells.

But numerous recombinases discovered by Bhatt and her graduate student Matthew Durrant have begun to change that. In 2019, they began recruiting a team that would include Stanford scientists Michael Bassik and Lacramioara Bintu, UC Berkeley scientist Patrick Hsu and graduate students Josh Tycko and Alison Fanton to help screen and test newly uncovered proteins.

The results, published in 2022, caught the attention of RA Capital Management and Khosla Ventures, which quietly backed Stylus Medicine with $40 million that year. New artificial intelligence tools emerging around the same time have allowed the startup to create recombinases never before seen in nature, which are built for editing human genes.

Recombinases could have many applications, but when Stylus emerged from stealth with an additional $45 million in May 2025, it announced a single-minded focus on engineering immune cells inside the body to fight cancer. The technique, known as in vivo CAR-T cell therapy, could eliminate the most expensive and onerous aspects of cell therapy.

It’s also a hot area for deals and venture capital. Three pharma companies acquired in vivo CAR-T startups earlier this year, and dozens of small startups are joining the race.

“The level of interest is higher than I’ve experienced in any field,” Stylus CEO Emile Nuwaysir told Endpoints News. But despite that, he says he’s undaunted by the competition. “Just because it’s crowded doesn’t mean it’s solved,” he added.

Nuwaysir sees limitations with his competitors’ approaches, including the durability of treatments that only use mRNA to temporarily reprogram immune cells, and the expensive manufacturing and potential safety risks of genes delivered by lentiviral therapies.

Stylus is going for a more durable approach, using its recombinase (encoded in an mRNA molecule) to permanently slip cancer-fighting genes (delivered as DNA) into immune cells. By packaging mRNA and DNA pieces into the same lipid nanoparticle, the synthetic system could be cheaper and more scalable than viral vectors.

But the company will have to pull off a trio of technical feats to get the approach to work. First, its lipid nanoparticles must selectively shuttle the medicine into T cells and avoid getting soaked up by the liver.

Once the cargo is unloaded, the therapy must traverse the cell’s interior and breach the nucleus without setting off any alarm bells — something that exposed DNA is prone to do. Nuwaysir said Stylus has a trick for clamping down that inflammation, but he’s not divulging the secret.

Finally, the company’s recombinases must accurately, efficiently and safely plop therapeutic DNA into the genomes.

Just a few years ago, solving any one of these puzzles — targeted nanoparticles, non-viral delivery of DNA, and a new gene editing system — could have been enough to build a company around. But with investor disillusionment in gene editing companies running high in 2025, Nuwaysir believes that all three must come together for the company to make an impact.

“To break through is to provide a medicine,” he said. “What we don’t want to do is just provide another technology.”

The 45-person company is still testing the approach in monkeys, but Nuwaysir is beginning to think about running the first clinical test in China, where investigator-initiated studies give drugmakers flexibility to test different doses and formulations of a drug at a fraction of the cost and time of traditional clinical trials.

If Stylus is eventually successful, Nuwaysir believes it could transform CAR-T therapy into something that helps not just thousands of people, but millions.

“It will change the paradigm when we get to the point where in vivo engineering is as safe and effective as a vaccine,” Nuwaysir said. “I want to be part of that future where those medicines are broadly available.”

Article originally published by Ryan Cross at Endpoints News.