Current Sickle Cell Disease Gene Therapy Treatments: Literature Review

Abstract

Sickle cell disease (SCD) consists of haemoglobin-mutation related blood disorders caused by mutations of the HBB gene. Current treatments for SCD are symptom-based or preventive treatments. The only curative treatment for SCD- an allogeneic hematopoietic stem cell transplant- is inaccessible to the majority of SCD patients. The transplant required a donor graft is unavailable for most individuals. Currently, research in gene therapy treatment for SCD attempts to provide long-lasting treatments in two distinct techniques. The first technique is to change the mutation-containing genotype to produce a normal or functional haemoglobin protein. The second technique is to bypass the production of the mutated adult haemoglobin and product fetal haemoglobin instead. This literature review compares three gene-editing methods; Lentiviral Vectors, CRISPR/Cas9, and Base Editors. A review of previously published research papers was conducted and compared over a 2 month period during a summer student research program to determine the progression of each of the three gene-editing methods in the two techniques of SCD gene therapy treatment. While all three were successful in both genotype correction and fetal haemoglobin induction, only the Lentiviral Vector and CRISPR/Cas9 treatments for fetal haemoglobin induction have published data on human trials. However, the Base Editor shows promise in its ability to surpass many issues faced with both viral vectors and CRISPR/Cas9 such as off-target DNA breaks. Progression in SCD gene therapy can provide a treatment option for all affected individuals and can even provide a basis for gene therapy for other blood disorders.