It would be an understatement to say that there are many diseases that humans are facing every day. Some of them we can solve or treat to minimize their effects on us. Some are incurable and to deal with them, we must consider and make very hard decisions on.
These diseases originate from an equally large amount of sources, be it bacteria, virus, random chance, or even genetically inherited. For those diseases with a genetic component or are affected by modifications to our genetics, we are entering an era of hope where these can be addressed. New technologies are currently being developed, improved, and extensively researched in order to prove their worth against the things that hurt us. In a recently published paper, scientists explored how genetic editing technologies can help against beta thalassemia, a blood disorder.
Understanding Beta Thalassemia
Beta-Thalassemia is a genetic disorder, of which there are many, that is fairly common worldwide. It is blood disorder that causes the body to produce low amounts of hemoglobin. Hemoglobin is a protein within our red blood cells that carries oxygen to the cells in our body. For people with beta thalassemia, the reduced hemoglobin results in lower amounts of oxygen in our blood and cells. It also results in lower amounts of red blood cells, which leads to anemia. The anemia and other problems of the disorder results in fatigue, weakness, pale skin, and other serious conditions, like increased risk of blood clots. There are two forms of beta thalassemia: beta thalassemia major (the severe form) and beta-thalassemia intermediate (the not so severe form).
According to the Genetics Home Reference, of the U.S National Library of Medicine, thousands of infants are born beta thalassemia every year and they are primarily located in areas of the Mediterranean, North Africa, Middle East, Central and Southeast Asia, and India. Because this is a genetically inherited disorder, children are greatly affected by this disorder, especially the major form of it as it appears much earlier in children versus the intermediate form. They develop life-threatening forms of the symptoms and face other severe problems like slowed growth rate, enlarged organs, and delayed puberty.
For those with beta-thalassemia major, they eventually need lifelong blood transfusions. While helpful, these blood transfusions result in accumulation of iron, which results in an increased occurrence of hormone, liver, and heart problems. Treatment for any form of the disorder usually includes blood transfusions, bone marrow transplant for major forms, medicines to address the iron accumulation, and continued monitoring and support.
The Technique
Researchers at Sun Yat-sen University in Guangzhou, China had an embryo with beta-thalassemia that was caused by point mutation in the HBB gene, which is responsible for hemoglobin and red blood cells. The researchers used a precise base editor technique to correct the point mutation. The mutation, resulting in the diseased state, was an incorrect G base in the HBB gene’s DNA code. The base editor changed that G to the correct A base.
The base editor technique is highly modified version of CRISPR that fills the areas which CRISPR cannot get to. CRISPR allows for precise gene editing that is also relatively easy to accomplish. Unfortunately, that precision does not go all the way down to single bases of DNA, which is of concern for some genetic diseases like beta thalassemia. According to David Liu, chemical biologist at Harvard University in Cambridge, a majority of disease-associated genetic variants are point mutations.
CRISPR uses an enzyme called Cas9 to cut and make changes to DNA. David Liu and his team turned off Cas9 and attached another enzyme to it that was able to chemically change one DNA base to another. They would then use a guide RNA to take the modified Cas9 to its target, where the chemical enzyme would change the DNA and not break it. They found that this worked well in isolated DNA strands, but did not work effectively in cells because it modified only a single strand and the cells eventually undid the changes using the other strand. To address this, they attached another enzyme onto the Cas9 that would fix the other strand. This would result in a fully converted DNA strand.
The Experiment
Puping Liang and the other researchers collected skin cells from patients with beta-thalassemia and used the base editor technique to modify the HBB genes, fixing the mutation. They then isolated the nucleus from those skin cells, to ensure that only the fixed DNA would be used, and transferred them into mature human egg cells. The researchers found that 23% of the embryos were corrected using this technique. While not lot, the researchers feel that it shows the feasibility of curing genetic disease in human cells and embryos by base editor system. None of the embryos were implanted or allowed to develop any further.
The Future
Despite the low success rate of the experiment, it showed the potential of this highly precise gene editing method. With more research and time, scientists could develop this technique to make changes at a higher success rate and also allow it to be used on other point mutation genetic diseases. The lessons learned from developing this method could also be used to further understand and develop CRISPR, the system that modified here.
These experiments on embryos and human cells represent the first step in a long line of steps it will take to eventually be used in humans. More animal trials and cell experiments are needed to ensure that these techniques and technologies create stable DNAs that will not result in worse issues. We must also begin to assess the ethics and science around gene editing on such precise scales.
It would be foolish to assume that after we successful begin to use these for human modifications, that we would only use them in medically necessary situations. Gene editing would also allow us to modify superficial traits, like height, hair color, eye color, or even skin color. We may even be able to modify genes that affect our weight, intelligence, and many other factors.