Gene Therapy for Sickle Cell Disease: Present Insights

Abstract

Sickle Cell Disease (SCD) is an inherited red blood cell disorder resulting from a single-point mutation. It results
in complications such as acute and chronic pain, infections, stroke, kidney disease, and heart failure that reduce
the quality of life not only for affected persons but also for their families. It can be treated with drugs and
bone marrow transplants, but there is no known cure for it. One of the potential cures is gene therapy, which
involves adding, editing or silencing and correcting genes by bioengineering techniques including CRISPR/Cas9
system; zinc finger nucleases (ZNFs); transcription activator-like effector nuclease (TALEN) technology; and
base editors. The therapy procedure involves the retrieval of affected genes from patient hematopoietic stem
cells, engineering them ex vivo and reintroduction into patients as therapeutic genes. Researchers have achieved
significant progress in the use of CRISPR technology by, amongst others, repressing BCL11A gene enhancers and
editing erroneous genes via base modifications as well as prime edits. This has proven effective in the reduction
of adverse impacts that SCD have on patients. Nonetheless, therapeutic genes can cause insertional mutagenesis
and cancer after integration into the patient. Finding a significant cure for SCD via gene therapy is in the clinical
stage; methods to combat therapeutic cancer-inducing genes, as well as expertise and infrastructure provision,
are highly required. Gene therapy for SCD has room for further research and development.