“Zinc fingers” may sound like the world’s worst candy bar, but these human proteins may hold the key to treating complex genetic diseases.
According to research led by NYU Grossman School of Medicine and the University of Toronto in Canada, a new artificial intelligence program aims to make zinc fingers easy to make.
Zinc fingers are adaptable proteins that can direct DNA repair by directing enzymes to excise faulty segments from a person’s DNA code, researchers said. They can also be used to tailor the activity of a gene.
However, working with the proteins is difficult because they form complex bonds with DNA. For any desired genetic change, researchers need to be able to see how each zinc finger interacts with its neighbor from a myriad of possible combinations.
To address this, researchers have developed ZFDesign, an artificial intelligence that uses a database of nearly 50 billion possible zinc finger-DNA interactions to model and design gene edits.
“Our program can identify the correct grouping of zinc fingers for each modification, making this type of gene editing faster than ever before,” lead author David Ichikawa said in a NYU press release. He is a former graduate student at NYU Langone Health in New York City.
This technology could accelerate the development of gene therapies for diseases like cystic fibrosis, Tay-Sachs disease and sickle cell anemia, all of which are caused by errors in the order of the letters of DNA that encode the operating instructions for every human cell, the researchers said.
They said zinc finger editing offers a potentially safer alternative to CRISPR, the Nobel Prize-winning gene editing tool used for purposes ranging from finding new ways to kill cancer to developing more nutritious plants.
Zinc fingers are entirely human, but CRISPR relies on bacterial proteins to interact with the genetic code. These proteins could trigger a patient’s immune system to identify them as foreign and attack them like a typical infection.
Zinc finger tools are also smaller and could offer more flexible gene therapy techniques compared to CRISPR, the researchers added.
“By accelerating zinc finger design coupled with their smaller size, our system paves the way for using these proteins to control multiple genes simultaneously,” said senior author Marcus Noyes, assistant professor of biochemistry and molecular pharmacology at NYU Grossman School of Medicine in NYC.
“In the future, this approach may help correct diseases that have multiple genetic causes, such as heart disease, obesity and many cases of autism,” he said in the press release.
However, Noyes warned that zinc fingers are still difficult to control. They are not always specific to a single gene, so some combinations can lead to unintended changes in the genetic code beyond the intended target.
Because of this, the team next plans to refine the AI program so it creates more precise zinc finger groupings that drive only the desired gene editing, Noyes said.
A report on ZFDesign was published online Thursday in the journal Nature Biotechnology.
More information
Harvard Medical School has more on zinc fingers.
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