Modelling the Applications of CRISPR-Cas9 for Treating Sickle Cell Disease.

Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR-associated protein 9 (CRISPR-Cas9) is a genome editing tool that can remove, modify, or add sections of DNA. It is made up of two main molecules: the Cas9 protein and the guide-RNA (gRNA), which is used to match a target gene to the CRISPR-Cas9 molecule. The desired sequence of DNA must be between 2 and 5 nucleotides and must be followed by the protospacer adjacent motif (PAM) at the 3' end of the gRNA. This enables the target gene to be found and cut by the Cas9 endonuclease. Once cut, the DNA can be repaired using non-homologous end joining (where a random insertion or deletion of DNA occurs) or homology directed repair (where a homologous piece of DNA is used as a template to repair the DNA). The latter is used for genome editing, as the target sequence can be changed with the CRISPR-Cas9 system. Sickle Cell Disease (SCD) is an autosomal recessive hereditary disorder that affects erythrocytes and is caused by a single base substitution of adenine to thymine on the hemoglobin beta (HbB) gene. Currently two different groups are examining two different techniques to treat SCD. One group has shown that by deleting the BCL11A gene, fetal hemoglobin production can occur, which greatly diminishes the amount of Sickle hemoglobin (HbS). An example of this application of CRISPR-Cas9 for treating SCD is the story of Victoria Gray, the first person to have received genome editing treatment for SCD.