Lab Tests Reveal Risks of Using Gene-Editing Tool on Embryos

Already the subject of many ethics debates, the gene-editing tool CRISPR led to the loss of whole chromosomes when used to reverse hereditary blindness in an embryo, new research reveals.

(CN) — Altering or attempting to “correct” any mutations in human embryos using the gene-editing tool CRISPR could lead to unanticipated or even undesirable results, researchers said in a study released Thursday. 

CRISPR is a genomic editing system that uses an enzyme to permanently cut strands of DNA, a process that allows scientists to modify genes in attempts to treat or prevent diseases.

Changes can also be made to the genomes of cultured cells, living tissues and animal embryos.

The tool has sparked rapid advances in molecular biology and its developers were honored for their work with this year’s Nobel Prize in chemistry.

A China-funded study released in 2019 showed small gains in the fight against HIV when it provided a man with the AIDS virus with CRISPR-altered blood cells that resisted the virus.

But the application of the tool has sparked ethical debates worldwide since, among other issues, it can cause unintended changes or genetic alterations that can pass to future generations. 

Chinese scientist He Jiankui was jailed after he used CRISPR in 2018 to create the world’s first gene-edited babies, a process widely denounced by governments and scientists as a dangerously early leap in genetic science.

The study published Thursday in the journal Cell extends into the debate with its detailed analysis of CRISPR.

Researchers examined CRISPR’s application in an experiment to repair the EYS (eyes shut homologa) gene, which causes hereditary blindness early in the development of a human embryo.

Study author Dieter Egli of Columbia University said in a statement released with the study that CRISPR’s application in that experiment often resulted in the elimination of entire chromosomes or huge segments of them.

“Our study shows that CRISPR/Cas9 is not yet ready for clinical use to correct mutations at this stage of human development,” Egli said. 

Study co-author Michael Zuccaro of Columbia University said in the statement the loss of entire chromosomes was a likely result from an intentional break in DNA.

“We know from previous studies in differentiated human cells and in mice that a break in the DNA results in mostly two outcomes: precise repair or small local changes,” Zuccaro said. “At the EYS gene, these changes can yield a functional gene, though it is not a perfect repair.”

Researchers also reexamined a separate 2017 study on the successful application of CRISPR in correcting a heart disease-causing mutation in human embryos.

The study released Thursday offered a different interpretation of the results: the chromosome carrying the mutation may have been unintentionally eliminated altogether.

“If our results had been known two years ago, I doubt that anyone would have gone ahead with an attempt to use CRISPR to edit a gene in a human embryo in the clinic,” Egli says. “Our hope is that these cautionary findings should discourage premature clinical application of this important technology, but can also guide responsible research to achieve its ultimate safe and effective use.”

Researchers did not immediately respond to a request for further comment on their study.

Due to the ban on using federal resources for research on human embryos, researchers funded the study with private contributions from the New York Stem Cell Foundation and the Russell Berrie Foundation.

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