A study about “correcting” several one-cell embryos using CRISPR technique was published in Nature journal this week. Researchers from US and Korea used a gene-editing technique called CRISPR in correcting mutated MYBPC3 gene, which is responsible for a heart disease called hypertrophic cardiomyopathy (HCM).
CRISPR technology, more completely known as CRISPR/Cas9, is a novel gene-editing technique which can cut, insert and correct DNA within a cell. The acronym stands for “Clustered Regularly Interspaced Short Palindromic Repeats”. The term “CRISPR” actually refers to clusters of repeating sequences found in DNA of bacteria and they are part of the immune system. When bacteria are attacked by viruses, they produce enzymes that fight the viruses, collect and cut the genetic codes of the dead attackers, and store the codes in CRISPR spaces.
Whenever viruses attack again, these bacteria produce special enzymes called Cas9 which contains the stored codes. If the codes carried by the Cas9 matched the codes of the viruses, the enzyme will proceed on cutting the new attackers into pieces. Researchers have found a way of inducing bacteria to produce Cas9 by feeding them artificial genetic codes. This is the foundation of CRISPR as a gene-editing tool where scientists can design enzymes that could cut and edit any DNA parts within a cell. Precision is what makes CRISPR better than other gene-editing tools.
One promising application of CRISPR lies in correcting genes of hereditary diseases like Huntington’s disease, cystic fibrosis, high cholesterol and cancers. The focus of the study is hypertrophic cardiomyopathy (HCM), characterized by thickening of heart muscles and affects 1 in 500 people worldwide. HCM-affected patients, which include young athletes, are not aware they have HCM until they experience sudden cardiac arrest. Although HCM can be cured with medication, the cause cannot be cured and this disease has 50% chance of being passed on to children.
To conduct the experiment, eggs are gathered from 12 healthy females and sperm from a male carrier of the mutated MYBPC3 gene. CRISPR is done simultaneously with fertilization and cuts out the mutated gene contained in the sperm. The embryos grew and 72% of their cells are “corrected” by using the non-mutated gene from the egg. Researchers are satisfied that no off-target corrections happened, which is a major concern for earlier CRISPR studies.
In 2015, China conducted earlier CRISPR studies for a blood disorder called beta thalassemia. The study, however, produced “mosaicism”, a situation where some of the embryo’s cells are corrected while some still have the mutated gene. The main difference in the technique here is that the China study applied CRISPR after fertilization while the US-Korea study applied the technique during fertilization.
Despite successes and possibilities of applications, gene editing is still a controversial topic. While the CRISPR study followed the recommendations of the National Academies of Sciences, Engineering and Medicine, it may take a while before legal and ethical barriers in conducting experiments on human DNA will be settled. There is fear of creating “designer babies” or altering the germline but there is also hope that fatal and debilitating hereditary diseases can be corrected with gene editing.