For Yale scientists Peter Glazer, Mark Saltzman and Marie Egan, September was a memorable month. Trucode Gene Repair, the biotech company they advised, received $34 million in venture funding.

The funding bolsters the Bay Area biotech company’s development of a novel gene-editing technology. Unlike other methods, their approach uses a nanoparticle gene-editing molecule that allows researchers to change DNA without removing any cells from an organism. Eventually, the scientists at Trucode hope that the technology will be used for incurable diseases such as cystic fibrosis and sickle cell disease.

“For diseases like cystic fibrosis — which affects the lung and the gut — you can’t take out the lung and the gut to edit genes outside the body,” Saltzman said. “To treat cystic fibrosis using gene therapy, we need to use in vivo approaches to do it within the body, and that’s where [our technology] can come in to address complicated problems like this.”

The technology has its roots at Yale, where in 2009, Saltzman and Glazer began collaborating on a new method of therapeutic gene editing. The two created synthetic molecules that hijack the cell’s built-in genetic repair system. When introduced into cells, the molecules form a triple DNA helix with the target sequence, causing the cell to target and delete the abnormal structure.

But their synthetic gene-editing molecules were too large to penetrate cells themselves, prompting Salzman, an expert in drug delivery, to design a novel solution. The team of researchers packed nanoparticles with the therapeutic molecules, creating an extremely small, dense package of gene-editing reagents that can pass freely through cells and reach the target DNA sequence. The development, Saltzman said, proved effective across cell types.

“We found that the particles can circulate, can go to remote regions of the body like the bone marrow and will edit cells inside the animal tissue,” Saltzman said.

Other companies take a less direct approach to gene editing. Usually, cells are removed from patients, treated and then injected back into the body. The Yale scientists’ system takes a less invasive approach that only requires an IV infusion of the gene-editing particles.

Adding to its merits, the new technology caused less side effects compared to more well-known gene-editing techniques such as CRISPR, according to Glazer. For example, there were fewer instances of other genes mistakenly being edited alongside the target gene.

The Yale collaborators’ publications caught the attention of scientists from nucleic acid manufacturer PNA Innovations. Recognizing the nanoparticle-delivered gene-editing technology as a potential driving force for a biotech company, PNA wanted to commercialize the technology, Glazer said. But first, the scientists needed a patent.

“Patents are an essential component of commercializing and advancing Yale discoveries because we must have intellectual property rights in order to attract investment for bringing it into the commercial sector,” said Glazer. “Yale’s Office of Cooperative Research has been instrumental to this whole process.”

Saltzman described Yale’s role in supporting faculty ventures was “absolutely critical.” In particular, John Puziss, the director of business development at the Office of Cooperative Research, directly facilitated the patent application process, Saltzman said.

“Once the Yale collaborators obtain their patent, the Yale Office of Cooperative Research reaches out to its contacts. The process can go one of two ways. A new startup can be created, or an existing company can license the technology. The Office of Cooperative Research is excellent at making these introductions,” Glazer explained.

In 2016 — seven years after they first began working on the landmark project — Salzman and Glazer successfully licensed their technology to an existing biotech company, Trucode Gene Repair. As members of its scientific advisory board, the Yale scientists are currently working toward advancing their approach to minimally invasive treatments for diseases.

Marie Egan, an expert in cystic fibrosis, is advising the clinical aspect of applying this technology to developing cystic fibrosis treatments.

Trucode’s technology also appears promising for accelerating the timeline of treatment, even at the stage of fetal development. The Yale scientists’ technology was successful in editing the genes of mouse embryos in utero of pregnant mice, which suggested that genetic disorders could be treated as early as during fetal development. According to Saltzman, this accelerated treatment timeline could tremendously improve the quality of life for patients suffering from genetic disorders, since the earlier the disease can be treated, the better the outcomes.

Though the U.S. Food and Drug Administration has not approved gene-editing therapies for use in humans, companies like Trucode are trying to push their technology through clinical trials to reach patients’ bedsides.

“It’s difficult to predict clinical trial timelines at this point, but we are working the best we can toward that goal,” said Glazer.

Trucode Gene Repair was founded in 2011.

 

Viola Lee | kyounga.lee@yale.edu