Scientists attack malaria in blood cells by altering parasite genes

Researchers have discovered it is possible to slow the development of the malaria parasite inside blood cells by altering its gene expression. They suggest that even drug-resistant strains, which are on the increase worldwide, may succumb to this technique.

The technique even slowed parasite development in strains that have developed resistance to common anti-malaria drugs.

The research team, from Yale University in New Haven, CT, reports its findings in the Proceedings of the National Academy of Sciences.

While huge gains have been made in the global fight to eradicate malaria, the disease still devastates lives and livelihoods, particularly in Africa, where nearly half a million children under the age of 5 die of the parasitic disease every year.

Effective tools to prevent and treat malaria do exist, but the emergence of parasite strains that are resistant to drugs and insecticides threatens to undermine hard-won progress.

Drug resistant strains are becoming a very serious problem in places like Southeast Asia.

People become infected with malaria through bites from female mosquitoes carrying a parasite called Plasmodium. Once inside the human body, the parasite multiplies in the liver then infects red blood cells.

If not treated quickly, malaria can become life-threatening by disrupting blood supply to vital organs. Every year, nearly 2 million people are sickened by malaria, and 600,000 die from the disease.

In their study paper, Prof. Altman and colleagues highlight the importance of understanding the biology of the malaria parasite, particularly its genes, as this could be a fruitful avenue for finding new drug targets.

New technique targets RNA to alter gene expression

Their work relates to the role of RNA (ribonucleic acid), which carries instructions from DNA for directing the synthesis of proteins that are crucial to the organism's growth and development.

In the study, the researchers found a way of easily altering the gene expression of Plasmodium falciparum - the most deadly of the malaria parasite strains known to infect humans - by targeting RNA.

The tool that they used to alter the expression of P. falciparum by RNA is called a morpholino oligomer (MO). Researchers use MOs to block the access of other molecules to specific sequences in RNA.

The researchers showed it is possible to use MOs to interfere with gene expression in P. falciparum in such a way that they disrupt the organism's development inside blood cells.

The research team demonstrated that the technique slowed parasite development even in strains that have developed resistance to two common anti-malaria drugs. In their paper, they conclude:

"The ease in design of the MO molecules presents a possibility for their use in large-scale genome functional analyses and possibly in malaria therapy."

In 1989, the research leader, Prof. Sidney Altman, a molecular biologist and professor at Yale was awarded the Nobel prize for discovering that RNA is also involved in helping chemical reactions in cells in a similar way to an enzyme. Before then, it was thought that only proteins could behave like enzymes and that RNA's role was limited to carrying genetic codes between parts of the cell.

References:

1.  Targeting protein translation, RNA splicing, and degradation by morpholino-based conjugates in Plasmodium falciparum, Aprajita Garg et al.,Proceedings of the National Academy of Sciences, doi:10.1073/pnas.1515864112, published online 8 September 2015, abstract.
2.  Yale University news release, accessed 9 September 2015.
3.  Additional source: World Health Organization (WHO), Malaria, accessed 9 September 2015.
4.  Additional source: Sidney Altman - Nobel Laureate for Work With RNA, Marc A. Shampo et al., Mayo Clinic Proceedings, doi: 10.1016/j.mayocp.2012.01.022, published October 2012, accessed 9 September 2015.