by Yasemin Cole
When it comes to life, spelling is very important. In our day to day life, we take spelling for granted with autocorrect on cell phones and grammar checks on word processing programs. You may be familiar with the As, Ts, Cs and Gs that make up our DNA. These nucleotides come together to create genes, similar to letters coming together to form words. Taken together, these words come together to create a recipe book of all genes essential for life. And if one of these “words” is spelled incorrectly, disease results. However, in the millions of cells in our body, this “spelling” is a critical step between normal cellular function and disease.
Sickle cell anemia is a rare blood disease that causes red blood cells to deform and bend (Figure 1). It affects approximately 100,000 people in the US and occurs in 1 out of 364 Black/African American Births or 1 in 16,300 Hispanic American births (CDC). Red blood cells contain an essential protein called hemoglobin and bring oxygen to all organs in the body. Hemoglobin makes our blood red and is structured precisely to carry one oxygen (O2) molecule to the organs. Unfortunately, in the case of sickle cell disease, hemoglobin is misfolded. One misfolded hemoglobin can stick to other misfolded hemoglobins, forming long and stiff fibers. Due to the stickiness of misfolded hemoglobin, the entire red blood cell can also change shape. These misshapen cells are prone to sticking to each other and can die, causing the lifespan of the red blood cells to be shortened (Figure 1). This causes a condition called anemia, which is when the number of blood cells in the body is low. These malformed cells can also block blood vessels throughout the body leading to incredible amounts of pain, called pain crises, and a lack of oxygen to organs. As you can see, a small change in a protein leads to an avalanche of problems in the red blood cells and blood vessels.
What is the cause of the malformed hemoglobin? A simple spelling mistake or a “mutation” in the gene coding for beta-globin, one of the main components of hemoglobin. More specifically, a single amino acid, glutamic acid, is changed to valine (Figure 1). This spelling mistake is inherited from both parents. With this knowledge, there have been efforts to create a gene therapy to fix the beta-globin gene. Using the individuals’ own stem cells, scientists expose them to a viral particle containing a healthy copy of the gene. These cells are then implanted back into the patient. Coming full circle, gene therapy is changing the misspelling of a single word in beta-globin into a word that is readable, creating a fully functional hemoglobin protein.
