AI Advances Customizable Protein Therapy for Genetic Diseases

Researchers at the NYU Grossman School of Medicine and the University of Toronto have developed a new artificial intelligence (AI) program that could enable the first simple production of customizable proteins called zinc fingers to treat diseases by turning genes on and off. The tool is expected to accelerate the development of gene therapies on a large scale.

Illnesses such as cystic fibrosis, Tay-Sachs disease, and sickle cell anemia are all caused by errors in the order of DNA base pairs, resulting in mutations. Scientists can, in some cases, correct these mistakes with gene editing methods, but some conditions are caused by problems in how the cellular machinery reads DNA (epigenetics). 

Genes utilize transcription factors that tell the cell how much of a specific protein to make. When this process goes awry, over- or underactive genes can contribute to diabetes, cancer, and neurological disorders.

Zinc-finger editing is one such method able to modify and regulate genes. Zinc fingers, one of the most prevalent protein structures in the body, can direct DNA repair by gripping onto scissor-like enzymes and instructing them to cut incorrect portions out of the code. Similarly, zinc fingers can latch onto transcription factors and nudge them in the direction of a gene section that needs control. Genetic engineers can adjust any gene's activity by altering these instructions.

A drawback, however, is that artificial zinc fingers are challenging to design for a specific task. Since these proteins bind to DNA in intricate combinations, researchers need to be able to determine how each zinc finger interacts with its neighbor for each desired genetic modification out of the many possible combinations. ZFDesign, a new tool created by the study's authors, gets around this problem by modeling and designing these interactions using AI.

The authors of the study suggest that, in addition to posing a lesser immunological risk, the zinc-finger tools' smaller size may offer more versatile gene therapy techniques than CRISPR, allowing for more methods of delivering the tools to patients' appropriate cells.

"By speeding up zinc-finger design coupled with their smaller size, our system paves the way for using these proteins to control multiple genes at the same time," says study senior author Marcus Noyes, Ph.D. "In the future, this approach may help correct diseases that have multiple genetic causes, such as heart disease, obesity, and many cases of autism."