A new study will explore how combining CRISPR with biomaterials can make the technology both safer and more effective for therapeutic use.
CRISPR is a powerful gene-editing tool that holds enormous potential for treating genetic diseases by allowing scientists to cut, replace, or delete mutations in DNA. It can also modify gene expression, temporarily amplifying or diminishing its effects.
Yet, despite its promise, applying CRISPR in patients presents significant challenges.
“CRISPR is difficult to control when you want to do gene editing in vivo, or directly in the patient,” said Tomas Gonzalez-Fernandez, an assistant professor of bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science who will be leading the research.
“In this case, it’s typically administered as a systemic injection, meaning it circulates throughout the entire body and can have adverse effects on areas other than the target tissue. It’s important to control where CRISPR goes, and when the CRISPR action takes place, so it doesn’t cause problems elsewhere in the body.”
Gonzalez-Fernandez secured funding through the National Science Foundation’s Faculty Early Career Development Program (CAREER) for the research.
Through laboratory experiments, Gonzalez-Fernandez and his team will investigate using hydrogels to help guide the technology to the appropriate target and dictate the timing of the CRISPR action—in other words, controlling where and when the therapy takes place. They’ll first study what happens when the biomaterial and CRISPR first come in contact.
“We want to better understand that interplay, and how we can optimise biomaterial properties, such as charge and porosity, to better control CRISPR delivery,” he said.
After that, they’ll examine how these encapsulated or functionalised materials interact with human cells.
“That’s the higher level of complexity we need to understand,” he said. “How does the interaction between these materials and cells influence the gene editing efficiency of CRISPR?”
To date, says Gonzalez-Fernandez, there has been very little research into how biomaterials could enhance CRISPR delivery. As such, this will be one of the first studies to study how both biomaterial design parameters and cell interactions affect CRISPR efficiency.
The ultimate goal is to design safer, more efficient therapeutics that could someday treat genetic diseases, including cancer, sickle cell anemia, cystic fibrosis, Alzheimer’s, Duchnene muscular dystrophy (DMD), and other chronic musculoskeletal disorders.
The FDA recently approved CRISPR to treat sickle cell disease, an inherited disorder that causes red blood cells to deform and block blood flow and can cause severe pain. The therapy was done ex vivo, or outside the body, and the modified cells were then implanted back into the patient.
“This was the first approved CRISPR therapy, and it was a huge success for sickle cell anaemia,” says Gonzalez-Fernandez. “But it was all done in the lab, which requires highly specialised facilities.”
He notes that a recent clinical trial where CRISPR was injected virally directly into a patient with DMD caused a fatal immunological response.
“The challenge is how can we make this therapeutic safer?” he said. “My answer for that is to use biomaterials. They can help pave the way for more localised therapies.”
“It feels good to know that the scientific community appreciates the direction my lab is going in, and the type of science I want to do,” he said.
Gonzalez-Fernandez is also designing an outreach initiative to engage high school students through what he calls “CRISPR in a Box.”
With support from the CAREER award, he will design simple, hands-on experiments to demonstrate how CRISPR can edit genes in bacteria— demystifying the technology and sparking curiosity in the process.
Gonzalez-Fernandez, also runs a YouTube channel, and as part of the grant will leverage the channel to further explain engineering concepts of human physiology to increase public understanding of gene editing technologies.
“Research has shown that people are against CRISPR, not because they’re inherently afraid of it, but because they don’t understand it. If we can better inform the public about what it is, and how we can make it safer and more efficient, we can ultimately increase acceptance of the technology,” said Gonzalez-Fernandez.