New Gene Map Reveals Potential Drug Targets for Malaria Treatment

Researchers at Harvard T.H. Chan School of Public Health and their collaborators have created a comprehensive map of all the genes essential for blood infections in Plasmodium knowlesi, a parasite that causes malaria in humans.

This map represents the most comprehensive classification of essential genes in any Plasmodium species to date. It serves as a crucial resource for identifying druggable parasite targets and understanding mechanisms of drug resistance—insights that could guide the development of new malaria treatments.

“We hope our findings mark a significant step forward for malaria research and control. With emerging drug resistance threatening the limited arsenal of antimalarial drugs, this map will be an invaluable tool to help researchers combat one of the world’s leading infectious disease killers.”

 Manoj Duraisingh, John LaPorte Given Professor, Study Co-Corresponding Author, Immunology and Infectious Diseases, Harvard University

The study was published in Science.

Each year, Plasmodium species cause approximately 249 million malaria cases worldwide, leading to around 608,000 deaths. One such species, P. knowlesi, is a zoonotic parasite capable of causing severe and potentially fatal infections. It is an emerging public health concern in Southeast Asia.

To construct the map, researchers used a powerful genetic technique known as transposon mutagenesis in P. knowlesi. This method allowed them to disrupt all non-essential genes required for growth in human red blood cells, identifying the genes crucial for the parasite’s survival.

This genome-wide approach provided key insights into the molecular requirements for parasite growth and revealed specific genes linked to resistance against existing antimalarial drugs.

“Mapping all essential genes in P. knowlesi gives us a deeper understanding of the parasite’s molecular strategies—how it grows, adapts to environmental changes, and responds to antimalarial treatments. This genetic blueprint will not only aid malaria researchers in designing biological studies but also help monitor and mitigate the emergence of drug resistance.”

 Sheena Dass, Postdoctoral Fellow and Study Co-First Author, Harvard University

Additionally, the study offers valuable insights into another major malaria-causing species, P. vivax. Due to its evolutionary link to P. knowlesi, findings from this research may help overcome challenges in studying P. vivax, which cannot currently be cultured or genetically manipulated—an obstacle in global malaria elimination efforts.