Gene Drives: Enabling disease resistance by tipping the Mendelian scales

mosquito-diagram

Schematic representation of a gene drive. Source: Scientific American

In November 2015, Anthony. A. James and Ethan Bier from the Irvine and San Diego campuses of the University of California released a report detailing their development of genetically engineered mosquitoes that were resistant to the malarial parasite, P. falciparum. They inserted a couple of genes into the mosquitoes that would prevent P. falciparum from colonizing them, thus reducing malarial transmission. This is a significant breakthrough in the field of genetic engineering because James and Bier utilized a technique known as a gene drive to ensure that 99% of the offspring received the modified genes, as opposed to the usual 50% dictated by Mendelian genetics.

The concept of gene drives was first proposed in the 1940s, as a means of reducing populations of disease-carrying insects. However, technical issues made implementation difficult. The recently established CRISPR-Cas9 system, which is a powerful DNA editing tool allowing scientists to insert, delete or replace specific DNA sequences across a range of species, has enabled researchers to bias Mendelian inheritance patterns and conduct highly effective gene drives.

Gene drives could play a huge role in eradicating infectious diseases such as malaria, dengue, Lyme disease and sleeping sickness, by modifying the DNA of the disease-causing/carrying organisms. Up until this point, however, gene drives have only been conducted in laboratories and their efficiency has yet to be tested in real world conditions. Critics point out that it is important to have a standby that could reverse the genetic modifications in the organisms if needed, before they are ready to be released into the world. Scientists are currently tackling this issue by working on a type of gene drive known as the reversal drive that will revert the modified DNA to its original state.

Another type of gene drive known as the crash drive could be used to drive invasive pests to extinction. The issue that crops up here is that of natural selection. Natural selection will favour the survival of wild-type organisms that are resistant to the gene drive. This could be countered by targeting multiple sites in the DNA and frequently releasing new gene drives.

While there are also ethical issues to be overcome, as with any genetically modified organism, the scientific community is optimistic about gene drives making it to the real world. “We’re a hop, skip and jump away from actual gene-drive candidates for eventual release,” said Kevin Esvelt from the Wyss Institute at Harvard, who is currently working on implementing gene drive safeguards.

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