CRISPR-Cas9 gene drive and conventional approaches for malaria control: A review of progress, challenges, and future prospects

ABSTRACT Malaria remains a global health challenge, having a steadily increasing incidence as well as death rate, particularly in sub-Saharan Africa. Modern methods of tackling malaria, which primarily include long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), and antimalarial drugs, are faced with a serious threat emanating from drug and insecticide/pesticide resistance, thereby undermining eradication efforts. This work extensively reviewed the current literature on conventional means of controlling malaria to unveil the impediments to their use and the urgent need for a permanent solution through innovative strategies. It also provided a detailed evaluation of gene drive technology based on the CRISPR-Cas9 system as a crucial complementary tool for malaria control. Additionally, this present study carefully evaluated the ethical issues related to this technology, as well as the ecological concerns regarding the production and release of gene drive modified organisms. The CRISPR-Cas9 system employs a sequence-specific endonuclease mechanism to generate targeted double-strand DNA breaks, forming the basis for precise gene editing and drive development, and utilises two fundamental strategies for vector control: population suppression, primarily aimed at reducing the mosquito population, and population replacement, which aims to spread genes that make mosquitoes refractory to the Plasmodium parasite.