A simplified method for altering malaria-related genes
In a significant breakthrough, scientists at MIT have successfully used the CRISPR genome-editing technique to disrupt a single gene in the malaria-causing Plasmodium falciparum parasite with a success rate of up to 100 percent. According to the researchers, this approach could significantly speed up the analysis of genes and boost efforts to develop new, targeted drugs and vaccines against malaria.
Malaria, caused by Plasmodium falciparum, is responsible for an estimated 219 million cases and 655,000 deaths annually. Although chloroquine and artemisinin are currently used as treatments, the parasite is becoming increasingly resistant to these drugs. To combat this, there is an urgent need to develop new drugs, but identifying potential genetic targets has proven difficult.
MIT biological engineer, Jacquin Niles, explains that half of Plasmodium falciparum's genome remains functionally uncharacterized, with approximately 2,500 genes whose functions are unknown. However, understanding these genes could lead to novel therapeutics, such as drugs or vaccines.
The new CRISPR-based approach exploits a set of bacterial proteins that protect microbes from viral infection. The system includes a DNA-cutting enzyme, Cas9, bound to a short RNA guide strand that targets a specific genome sequence. By altering the RNA guide strand sequence, scientists can target and delete any gene of interest, providing a more efficient method for studying gene functions.
This technique significantly reduces the time it takes to determine the function of a single gene, which in the past could take up to a year. Previously, the time-consuming approach relied on homologous recombination, a type of genetic swapping that occurs rarely in the genome of the malaria parasite.
The paper's lead author is Jeffrey Wagner, a recent PhD recipient and current MIT postdoc in biological engineering. Other contributors to the research include graduate student Randall Platt, recent PhD recipient Stephen Goldfless, and Feng Zhang, the W.M. Keck Career Development Assistant Professor in Biomedical Engineering.
The findings were published in the August 10 online edition of Nature Methods. According to Niles, this breakthrough could revolutionize the field by enabling rapid and precise genome editing, thereby accelerating the discovery of new targets and the development of more effective treatments against Plasmodium falciparum.
By efficiently editing the parasite's genome, researchers can validate potential drug targets, study how changes in the parasite's genetic makeup affect its behavior and survival, create genetically modified parasites as potential live attenuated vaccines, and identify novel targets for antimalarial drugs. These advancements could lead to more targeted therapies and safer, more effective vaccines.
- This groundbreaking genetics research at MIT, published in the August 10 online edition of Nature Methods, involves the use of CRISPR genome-editing technique to disrupt genes in the malaria-causing Plasmodium falciparum parasite.
- The new CRISPR-based approach, led by the paper's lead author Jeffrey Wagner (a recent PhD recipient and current MIT postdoc in biological engineering), offers a more efficient method for studying gene functions, significantly reducing the time it takes to determine the function of a single gene.
- The advancements in engineering and genetics, such as the CRISPR technique, could revolutionize the field of medical-conditions like malaria by enabling rapid and precise genome editing, thereby accelerating the discovery of new targets and the development of more effective treatments against Plasmodium falciparum.
- In the realm of health-and-wellness and science, this research could lead to more targeted therapies and safer, more effective vaccines, contributing significantly to the fight against malaria, a disease responsible for an estimated 219 million cases and 655,000 deaths annually.
