Erythrocyte-Plasmodium interactions: genetic manipulation of the erythroid lineage

Targeting critical host factors is an emerging concept in the treatment of infectious diseases. As obligate pathogens of erythrocytes, the Plasmodium spp. parasites that cause malaria must exploit erythroid host factors for their survival. However, our understanding of this important aspect of the malaria lifecycle is limited, in part because erythrocytes are enucleated cells that lack a nucleus and DNA, rendering them genetically intractable. Recent advances in genetic analysis of the erythroid lineage using small-hairpin RNAs and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) in red-blood cells derived from stem cells have generated new insights into the functions of several candidate host factors for Plasmodium parasites. Along with efforts in other hematopoietic cells, these advances have also laid a strong foundation for genetic screens to identify novel erythrocyte host factors for malaria.