Chinese researchers alter embryonic genes

ALEX HABER
Staff Writer

PHOTO COURTESY OF WIKIMEDIA COMMONS THE Cas-1, -2, -3 proteins are pictured above. These nucleases cleave genes in the nuclei of cells.  The Cas-9 protein is used in a new molecular biology technique known as clustered regularly interspersed short palindromic repeats, abbreviated CRISPR.

PHOTO COURTESY OF WIKIMEDIA COMMONS
THE Cas-1, -2, -3 proteins are pictured above. These nucleases cleave genes in the nuclei of cells. The Cas-9 protein is used in a new molecular biology technique known as clustered regularly interspersed short palindromic repeats, abbreviated CRISPR.

Genetically altering humans has been a controversy over the last 20 years as our methods for controlling genes have become more refined. Up until this point, however, all gene manipulation has been done on live humans. Gene therapy is one method commonly used to aid the treatment of individuals afflicted with genetic diseases. Pupin Lang, Ph.D., published an article in Protein and Cell discussing findings on the use of the CRISPR/Cas9 in alteration of tripronuclear embryos, on April 1. The article, entitled “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes,” has invoked controversy since its publication.

Genetic engineering is prohibited in China on healthy embryonic zygotes. The laboratory at Guangdong Province Key Laboratory of Reproductive Medicine was granted access to tripronuclear zygotes destined for destruction because the zygote would not fully develop. Tripronuclear zygotes are formed from the combination of one egg and two sperm. The resultant zygote contains three pronuclei, the term for the nuclei of a zygote during fertilization prior to the combination of parental DNA to form a diploid cell. The presence of extra genetic material leads to genetic instability and the eventual loss of the child if the zygote had been implanted.
Scientists at the laboratory wanted to explore the possible use of the gene modification technique known as CRISPR/Cas-9 in removing mutated segments of DNA, thus saving the zygote from deformities and death. CRISPR/Cas-9 works by targeting certain genes in the nucleus and cleaving them using the nuclease Cas-9. Cas-9 cuts the target gene out of the DNA strand so a desired gene can be inserted. The technique yields several benefits including the removal of mutations inside live cells and the replacement of the DNA segment with the correct gene. Past studies have illustrated the usefulness of the technique.

Lang’s study presented evidence suggesting that the method can indeed remove the intended mutations and resolve issues in the embryo. There were some issues in their results, in which the method removed non-target genes from the genome. Lang concluded by noting that a refinement of the technique is needed to make the targeting molecule more selective to the mutations. Many of the embryos failed to take up the new DNA strand into their genome. This rejection compounded with the accidental addition of other mutations, the technique has a long way to go before application to healthy embryos.

A fierce debate has begun over the ethics of using such a method on human embryos. Several journals, including Nature and Science, rejected the manuscript over ethical objections. Many critics of the study claim that the technique may have potentially unethical applications. Potential misuse of the technique causes concern over the effects on genetic diversity or the unethical use of the technique to alter humans in a variety of ways. The debate about gene editing in humans will continue to be a sensitive issue in the years to come.

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