Question

In humans, Sickle Cell Disease is caused by a mutation in the gene encoding the beta subunit (Hbb) of hemoglobin, the oxygen transporting protein in the blood. The most common mutation is E6V (Glutamate6-to-Valine). If you were asked to design gene editing guide that will correct the mutation by inserting a codon for phenylalanine, what codon would most likely result in the greatest level of expression of the corrected Hbb? Briefly state why the level is likely to be highest with that codon.

Answer 1

1. The Sickle cell disease is a single-gene mutation caused due to single DNA base substitution in the gene that encodes the beta subunit of hemoglobin (Hbb).  This protein is responsible for transporting oxygen in the blood.
2. There are several gene-editing approaches as follows:

• The first approach involves editing one copy of the mutant beta-globin gene in Induced pluripotent stem (iPS) cells. Induced pluripotent stem cells like skin fibroblasts are grown in vitro with growth factors and transcription factors to develop desired red blood type cells. The mature red blood cells will have a copy of altered DNA.

• The second approach involves trimming of an enhancer gene called BCL11A  from fetal to adult hemoglobin which enables some of the functioning fetal types but removes sickled adult beta-globin.

• The third approach involves, editing the beta-globin gene in hematopoietic stem cells from sickle cell disease patients. The scientists use single guide RNA with single strands of DNA to target the beta-globin gene for delivering through viruses and liposomes