Researchers at the University of Michigan Engineering and Michigan Medicine announced on Mar. 31 that they have successfully used protein nanoparticles to genetically modify several types of human cells, offering a potential alternative to viral vectors in gene therapy.
The development could help reduce side effects commonly associated with virus-based gene therapies, such as secondary cancers and immune system overreactions. Gene therapy has been effective for treating blood disorders like sickle cell disease and leukemia, but using viruses as delivery agents can sometimes lead to unwanted complications.
In their proof-of-concept study published in Advanced Materials, the team demonstrated that liver cancer cells, kidney cells, and immune cells could be modified by introducing genes for green fluorescent protein via nanoparticles. “There are a lot of diseases where a protein is missing or dysfunctional due to a single mutation, and we can definitely correct for that by introducing a new gene,” said Joerg Lahann, Wolfgang Pauli Collegiate Professor of Chemical Engineering and director of the U-M Biointerfaces Institute. Lahann added: “Typically, this is done with viruses, but the viruses can be toxic and activate the immune cells. So there has been a push in the field to replace virus-based gene editing strategies.” The research was funded by the National Institutes of Health.
The nanoparticles developed do not insert genetic material into patients’ genomes as viruses do; instead, they deliver DNA or RNA that remains separate from cellular DNA. This method may help avoid new cancers linked to viral insertion breaking tumor-suppressing genes. The outer coating made from serum albumin—a natural blood component—may also prove safer than fat-based (lipid) nanoparticles currently used in some treatments.
The process involves mixing proteins with genetic material in water before applying an electric field through electrohydrodynamic jetting to form particles encased with polyethylenimine for stability. After entering target cells via endosomes and being digested, these particles release their genetic cargo without integrating it permanently into cell DNA—meaning repeated doses may be needed unless combined with CRISPR-Cas9 technology.
Co-author Michael Triebwasser said future work could explore targeting specific cell types using different proteins on nanoparticle surfaces. Fjorela Xhyliu stated: “In future studies, we hope to test the nanoparticles’ ability to modify human cells with therapeutic genes and identify potential side effects.” The experiments were conducted at facilities supported by federal grants at University of Michigan Ann Arbor.
The University of Michigan Ann Arbor stands as a public research university offering diverse academic programs across its schools and colleges according to its official website. Its main campus is located in Ann Arbor with additional sites in Dearborn and Flint according to its official website. The institution extends its reach through these campuses while cultivating leaders who address challenges beyond Michigan according to its official website.
