Malaria is one of the world’s leading health problems. More than 40 percent of the world’s population live in areas where there is a risk of contracting the disease. According to the Centers for Disease Control & Prevention, 300 million to 500 million cases of malaria occur each year, and nearly 1 million people die of the disease annually, largely infants, young children and pregnant women, most of them in Africa.
Earlier studies from the lab focused on engineering anti-disease mosquitoes. Their anti-dengue fever models were tested in cage trials in Mexico, and in 2012, their results showed that antibodies that impair the parasite’s biology adapted from the immune systems of mice can be introduced into mosquitoes. This trait, though, could only be inherited by about half of the progeny. Earlier this year, whilst working with fruit flies, the group announced the development of a new method for generating mutations in both copies of a gene. This mutagenic chain reaction involved using the Crispr-associated Cas9 nuclease enzyme and allowed for transmission of mutations through the germ line with an inheritance rate of 95 percent. The current study packaged antimalaria genes with a Cas9 enzyme, which can cut DNA, and a guide RNA to create a genetic ‘cassette’ that targeted a highly specific spot on the germ line DNA to insert the antimalaria antibody genes in a a mosquito embryo.
The current study inserted a DNA element into the germ line of Anopheles stephensi mosquitoes, a leading malaria vector in Asia, that resulted in the gene preventing malaria transmission being passed on to offspring. The team stress that to ensure that the element carrying the malaria-blocking antibodies had reached the desired DNA site, they included in the cassette a protein that gave the progeny red fluorescence in the eyes. Results show that almost 100 percent of offspring, 99.5 percent, to be exact, exhibited this trait.
The team surmise that their findings underline the growing utility of the Crispr method, a powerful gene editing tool that allows access to a cell’s nucleus to snip DNA to either replace mutated genes or insert new ones and opens up the real promise that this technique can be adapted for eliminating malaria. For the future, the researchers state that further testing will be needed to confirm the efficacy of the antibodies and that this could eventually lead to field studies. They go on to conclude that the mosquitoes developed are not the final brand and this technology will them to efficiently create large populations.
Source: UC Irvine Strategic Communications