Integrating CRISPR and biomaterials engineering: Paving the way for safer gene therapies

(Press-News.org) 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 (which is a reagent, or a substance that facilitates a reaction) in patients presents significant challenges.

“CRISPR is difficult to control when you want to do gene editing in vivo, or directly in the patient,” says Tomas Gonzalez-Fernandez, an assistant professor of bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science. “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 recently secured funding through the National Science Foundation’s Faculty Early Career Development Program (CAREER) for his research that will explore how combining CRISPR with biomaterials can make the technology both safer and more effective for therapeutic use.  

The prestigious NSF CAREER award is given annually to early-career faculty members across the U.S. who exemplify the role of teacher-scholars through outstanding research, excellent education, and the integration of education and research. Each award provides stable support at the level of approximately $500,000 for a five-year period.

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 optimize biomaterial properties, such as charge and porosity, to better control CRISPR delivery,” he says. 

After that, they’ll examine how these encapsulated or functionalized materials interact with human cells.

“That’s the higher level of complexity we need to understand,” he says. “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 anemia,” says Gonzalez-Fernandez. “But it was all done in the lab, which requires highly specialized facilities.”

He notes, too, 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 says. “My answer for that is to use biomaterials. They can help pave the way for more localized therapies.”

The CAREER award is validation of that belief. 

“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 says.

Beyond the lab, he’s 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.”

About Tomas Gonzalez-Fernandez Tomas Gonzalez-Fernandez, an assistant professor of bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science, leads research at the intersection of synthetic biology, biomaterials, and tissue engineering. His work focuses on developing smart materials and stem cell-based strategies to enhance the regeneration of musculoskeletal tissues, including bone, cartilage, and tendon. In his lab, Gonzalez-Fernandez integrates cutting-edge technologies such as CRISPR/Cas9, 3D printing, and novel bioinks to explore applications like in situ gene editing for tissue repair, engineering immunomodulatory cells and materials, and advancing 3D and 4D bioprinting of functional tissue grafts.

Gonzalez-Fernandez earned his PhD in mechanical and manufacturing engineering from Trinity College Dublin (Ireland), where he specialized in combining non-viral gene therapy with 3D bioprinting for tissue regeneration. He continued his research as a postdoctoral fellow at the University of California, Davis, where he investigated biomaterial functionalization for bone and cartilage repair, earning recognition as a Rising Star in Engineering and Health by Columbia University. 

Alongside his research, Gonzalez-Fernandez contributes to professional organizations such as BMES and ORS, serves on Lehigh's DEI council, and co-chairs the university’s Faculty and Staff Pride Network.

Related Links:  Faculty Profile: Tomas Gonzalez-Fernandez Tomas Gonzalez-Fernandez Lab: Advanced Tools for Engineering Smart Cells and Materials NSF Award Abstract (# 2441592): CAREER: Multilevel Understanding of Biomaterial-Guided CRISPR Delivery YouTube: Prof. Tomas Gonzalez-Fernandez Institute for Functional Materials and Devices  

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