CRISPR Cas9, a gene-editing technology, might not have been the ultra-precise device that researchers thought.
According to a growing body of evidence, the technology, which allows researchers to delete, substitute, or insert new DNA sequences into a cell's genetic code, often causes unintended genetic changes.
Scientists at the Francis Crick Institute published the most recent research demonstrating these errant on-site edits (FCI).
The study is titled "Frequent Loss-of-Heterozygosity in Crispr-cas9-Edited Early Human Embryos."
HALLE, GERMANY - AUGUST 14: A technician holds vials containing engineered DNA that will be introduced into the leaves of nicotiana benthamiana plants, which are a close relative of tobacco, in a lab at the facilities of Icon Genetics on August 14, 2014, in Halle, Germany. Icon Genetics has developed a process to produce proteins and enzymes via the nicotiana benthamiana plant that will be used in the production of antibodies for ZMapp, which is being heralded as a possible cure to the ebola virus.
Is There Something Wrong With CRISPR?
According to the study they reported in the journal PNAS on Friday, they looked back at previous CRISPR studies, including their own. The researchers then noted an alarming 16 percent featured unintended gene edits.
Meanwhile, another team of researchers used gene expression as a tool to verify the claim. Epigenetics is periodically turning on and off genes in the genome by adding primary chemical groups.
Whitehead Institute's Weissman Lab created a CRISPR on and CRISPRoff technologies that can target particular genes and turn them on or off without modifying the DNA code.
They published their research, "Genome-Wide Programmable Transcriptional Memory by Crispr-Based Epigenome Editing," in the journal Cell.
DNA methylation is a vital epigenetic mechanism that involves adding a methyl group to a gene, effectively blocking it from being read by the cell - if the gene is covered, it will not be converted into a protein. The gene will then be "silenced."
Diseases will result if something goes wrong. Prader-Willi syndrome, Fragile X syndrome, and certain cancers are among the disorders related to this activation or silencing.
"The big story here is we now have a simple tool that can silence the vast majority of genes," says Weissman in a statement.
"We can do this for multiple genes at the same time without any DNA damage, with a great deal of homogeneity, and in a way that can be reversed. It's a great tool for controlling gene expression."
Importance of This Research
FCI Human Embryo and Stem Cell Laboratory group leader and senior study author Kathy Niakan said in a press release that their work highlights the importance of checking unintended mutations to understand what changes have happened in any human cell type,"
Previous experiments on gene-edited human embryos donated by people who were seeking fertility treatments but didn't need them were examined in the new study. The fact that these CRISPR Cas9-induced DNA edits went completely unnoticed at the time is particularly concerning.
"Conventional tests used to check the accuracy of CRISPR-Cas9 can miss the types of unintended on-target mutations we identified in this study," lead study author and former postdoctoral researcher at the FCI's Embryo and Stem Cell Laboratory Gregorio Alanis Lobato said in the =release. "There's still so much for us to learn about the effects of CRISPR-Cas9 technology and while this valuable tool is refined, we need [to examine all changes thoroughly.]"
That means that studies previously thought to be promising demonstrations of CRISPR Cas9's precision could have actually been rife with potentially harmful errors that, in extreme cases, may even lead to cancer - implying that scientists must be confident their gene-editing work is error-free before putting it into a clinical environment.
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