Wirelessly Hacking Gene to Reprogram Human Genome

A new UB-led study describes how researchers wirelessly controlled FGFR1 — a gene that plays a key role in how humans grow from embryos to adults — in lab-grown brain tissue.

The ability to manipulate the gene, the study’s authors say, could lead to new cancer treatments and ways to prevent and treat mental disorders such as schizophrenia.

The study was reported in the July issue of the Proceedings of the Institute of Electrical and Electronics Engineers.

It represents a step forward toward genetic manipulation technology that could upend the treatment of cancer, as well as the prevention and treatment of schizophrenia and other neurological illnesses.

It centers on the creation of a new subfield of research the study’s authors are calling “optogenomics,” or controlling the human genome through laser light and nanotechnology.

For the past 20 years, scientists have been combining optics and genetics — the field of optogenetics — with a goal of employing light to control how cells interact with each other.

By doing this, one could potentially develop new treatments for diseases by correcting the miscommunications that occur between cells. While promising, this research does not directly address malfunctions in genetic blueprints that guide human growth and underlie many diseases.

The new research begins to tackle this issue because FGFR1 — it stands for Fibroblast Growth Factor Receptor 1 — holds sway over roughly 4,500 other genes, about one-fifth of the human genome, as estimated by the Human Genome Project, says study co-author Michal K. Stachowiak, PhD, professor of pathology and anatomical sciences.

“In some respects, it’s like a boss gene,” he says. “By controlling FGFR1, one can theoretically prevent widespread gene dysregulations in schizophrenia or in breast cancer and other types of cancer.”

The research team was able to manipulate FGFR1 by creating tiny photonic implants. These wireless devices include nanolasers and nanoantennas and, in the future, nanodetectors.

Researchers inserted the implants into the brain tissue, which was grown from induced pluripotent stem cells and enhanced with light-activated molecular toggle switches. They then triggered different laser lights — common blue laser, red laser and far-red laser — onto the tissue.

The interaction allowed researchers to activate and deactivate FGFR1 and its associated cellular functions — essentially hacking the gene.

The work may eventually enable doctors to manipulate patients’ genomic structure, providing a way to prevent and correct gene abnormalities, says Stachowiak, who also holds an appointment in the Department of Biomedical Engineering, a joint program between the Jacobs School of Medicine and Biomedical Sciences and the School of Engineering and Applied Sciences.

“The potential of optogenomic interfaces is enormous,” says co-author Josep M. Jornet, PhD, associate professor of electrical engineering in the School of Engineering and Applied Sciences. “It could drastically reduce the need for medicinal drugs and other therapies for certain illnesses. It could also change how humans interact with machines.”

Along with Jornet and Michal Stachowiak, the study was led by Yongho Bae, PhD, assistant professor of pathology and anatomical sciences; and Ewa K. Stachowiak, PhD, assistant professor of pathology and anatomical sciences.

The development is far from entering the doctor’s office or hospital, but the research team is excited about next steps, which include testing in 3D “mini-brains” and cancerous tissue.

Grants from the U.S. National Science Foundation supported the work.

Aesha Y. Desai, PhD, a former postdoctoral associate in the Department of Pathology and Anatomical Sciences, is also a study co-author.

Additional study co-authors from the Jacobs School are:

• Brandon S. Decker, a doctoral student in the genetics, genomics and bioinformatics program
• Christopher R. Handelmann, a master’s student in the genetics, genomics and bioinformatics program

Additional study co-authors from the Department of Electrical Engineering are:

• Pei Miao, doctoral student
• Amit Sangwan, doctoral student

Anna Balcerak, of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Poland; and Liang Feng, PhD, of the University of Pennsylvania, are also study co-authors.