Exploring the Potential of CRISPR-Cas9 Gene Editing for Sickle Cell Disease and Malaria Resistance: A Systematic Review

Abstract

Background: Sickle cell disease (SCD) and malaria remain major health challenges in sub-Saharan Africa. CRISPR-Cas9 has enabled advances in SCD gene therapy and malaria-related experimental research, but these applications represent distinct biological and translational pathways. This systematic review evaluated CRISPR-Cas9 applications in SCD and malaria research while distinguishing clinical therapeutic evidence from experimental malaria-related findings. Methods: A systematic review was conducted following PRISMA 2020 and Joanna Briggs Institute guidance. PubMed, ScienceDirect and Google Scholar were searched on 12 August 2026. Studies investigating CRISPR-Cas9 applications related to SCD or malaria, including HBBcorrection, fetal haemoglobin induction, host-cell modification, parasite genome editing and mosquito-vector modification, were included. Data were synthesised narratively due to substantial heterogeneity among study designs and outcomes. Results: Thirteen studies were included, comprising six SCD-related and seven malaria-related studies. SCD studies demonstrated progression from experimental genome correction and haemoglobin regulation strategies to clinical application of CRISPR-edited autologous haematopoietic stem and progenitor cells. Malaria-related studies primarily investigated parasite functional genomics, erythrocyte invasion mechanisms and mosquito genetic modification. No included study evaluated a single CRISPR-Cas9 intervention that simultaneously treated SCD and enhanced malaria resistance. Conclusion: CRISPR-Cas9 represents an advancing therapeutic platform for selected SCD applications and an important experimental tool in malaria research. Current evidence supports separate translational pathways, with clinical progress established in SCD and malaria applications remaining predominantly preclinical.