AUG 27, 2019 3:19 PM PDT

Using CRISPR to Edit the DNA Carried by Human Sperm

WRITTEN BY: Carmen Leitch

Most researchers would agree that we still have a lot to learn about the CRISPR gene-editing tool before we try it on human embryos, especially if there is not some dire need. But work has gone on anyway in a Chinese lab, and earlier this year a Russian researcher announced that he was going to attempt similar experiments. Many other scientists have suggested that a global moratorium should be implemented on genome edits in humans that are heritable.

The CRISPR/Cas9 complex cuts DNA / Credit: From animation by Visual Science and Skoltech

However, in work published last year and publicized recently by NPR, researchers at Weill Cornell Medicine in New York City are developing a method for using CRISPR to modify human sperm. They want to prevent certain genetic disorders, such as male infertility, which are passed from fathers to their children. In a conceptual study they published last year, they used CRISPR to target the gene LAMA1 in sperm cells. The gene is expressed at higher than normal levels in infertile men. They also want to target BRCA2, which is linked to an increase in the risk of some cancers.

While this research is sure to generate controversy, the scientists are confident. "I think it's important from the scientific point of view to investigate in an ethical manner to be able to learn if it's possible," said Gianpiero Palermo, a professor of embryology in obstetrics and gynecology at Weill Cornell Medicine. This work is being performed in his lab. "If we can wipe out a particular gene, it would be incredible," he added. "Theoretically, in principle, this would be a major, major benefit to society."

While that may be true, male infertility seems like a strange place to start if your true goal is to help the world. NPR consulted a researcher who was not involved in this work for comment.

"Male infertility is a very common condition," said Kyle Orwig, a professor in the department of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. "And there are some diseases that are incredibly devastating to families. And for those diseases, for me, if you could get rid of it, why wouldn't you get rid of it?"

Related: Russian Scientist Plans to Create More Genetically-edited Humans

First, the researchers have to successfully deliver the CRISPR reagents to sperm, which is challenging. In their journal report, they attempted to use high-voltage current to help the process along. The researchers have to find a balance between shocking the sperm too much and rendering them unable to swim, but enough that the reagents are able to enter the sperm cell.

"The hope is that the shock will cause the sperm to kind of loosen up a little bit for just a moment," explained June Wang, a Weill Cornell Medicine lab technician. "When the cell loosens up, the CRISPR gene-editing tool will hopefully get inside."

They are now moving beyond targeting male infertility genes. In current experiments, Wang is targeting the cancer susceptibility gene BRCA2. The study is ongoing, and we will surely be hearing more if the researchers disable the impact of the gene.

"Nobody's tried to do CRISPR on sperm before, so we have to try to figure out the right way to do it," Wang said.

One of the researchers that helped develop the CRISPR/Cas9 tool, Jennifer Doudna, a Li Ka Shing Chancellor Chair Professor in the Department of Chemistry and the Department of Molecular and Cell Biology at the University of California, Berkeley, discusses the technology in the video above. Some of the ethical concerns that have arisen from the use of CRISPR are outlined in the video below.

Sources: NPR, Fertility and Sterility

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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