Study: CRISPR Gene-Editing Ignites Tons Of Unintentional Genetic Mutations

CRISPR-Cas9 gene-editing has been hailed as one of the biggest scientific breakthroughs of our lifetime.

The technology is often called “molecular scissors” for its ability to “cut and paste” pieces of DNA, thereby removing unwanted traits and replacing them with more desirable ones. CRISPR is being celebrated for its accuracy, but a recent study sheds light on some imperfections surrounding the technology that we should be aware of.

When researchers at Columbia University used CRISPR-Cas9 to correct blindness in mice, they found that the process did successfully edit the gene responsible for blindness. However, it also caused unintentional mutations to more than 1,000 other genes. It’s exactly what critics of the technology have been warning about – that in the process of “fixing” part of the human genome, scientists could actually wind up doing irreparable damage. [1]

Study co-author Stephen Tsang, M.D., Ph.D., associate professor of ophthalmology, pathology, and cell biology at CUMC, Columbia’s Institute of Genomic Medicine, and the Institute of Human Nutrition, said:

“We feel it’s critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single-nucleotide mutations and mutations in noncoding regions of the genome.” [2]

CRISPR alters specific DNA sequences, but fails to correct the side effects that occur as a result.

There are currently 2 clinical trials involving humans underway in China, and a U.S. trial is slated to begin sometime next year. As many as 20 trials are in the works. One of the trials is aimed at preventing cervical cancers by using CRISPR to target and destroy the genes of the human papillomavirus (HPV) that cause tumors. [1] [3]

Here is a video talking a little bit about CRISPR.

 


Scientists identify areas likely to be affected by off-target DNA mutations with the assistance of predictive computer algorithms. Refinements to the technology suggested that in those trials off-target effects would be few. But nobody knows for certain how many side effects will result, or how serious they will be, and many experts are convinced the technology is simply not safe for use in humans at this point in time. [2]

Alexander Bassuk, M.D., Ph.D., the study’s co-author and professor of pediatrics at the University of Iowa, said:

“These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole-genome sequencing (WGS) has not been employed to look for all off-target effects in living animals.”

In the experiment in mice, researchers learned that success in the lab doesn’t always translate into success in the real world. The team looked at mice that they had previously corrected a blindness-associated gene in and sequenced their entire genome to find changes.

Though the mice’s vision was restored, 2 of them were left with over 1,500 unintended mutations, and more than 100 deletions and insertions of genes the researchers never intended to touch. What’s more, the computer algorithm failed to predict any of them. [1]

Outwardly, the mice didn’t look any different or develop any superpowers. But how the mutations will impact the mice in the future, or in subtle ways, remains an unanswered question for now. The vast majority of genetic mutations are not good. They’re exactly what CRISRP is intended to treat.

One scientist warned in January 2017 that gene-editing has the potential to “ruin human evolution.” Obviously, others see it as a promising advancement for the future.

The researchers concluded:

“This finding warns that CRISPR technology must be further tailored, particularly before it is used for human gene therapy.”



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