What are gene drive organisms?

Evolution takes time: it takes many generations before changes take hold in nature. Evolution often occurs via sexual reproduction, which recombines genetic material in each generation. New characteristics are in constant competition with older ones, and chance decides which variant of a trait is passed on. According to Mendel’s laws of inheritance, the probability that a new variant of a given trait is passed on to the offspring is 50 percent.

In 2003, the British researcher Austin Burt formulated the idea that genes can spread rapidly if they overwrite competing variants. The natural evolutionary process then no longer works: humans can change the genetic material of free-living organisms and spread new characteristics to serve their purposes.

So-called selfish genetic elements are found in the genetic material of all living beings. To our understanding, they do not contribute to the survival of the organism, but strive only to perpetuate themselves. Numerous protective mechanisms restrict the reproduction of these elements and limit the damage to the living being. In the course of evolution, a peaceful coexistence has usually developed, with selfish elements becoming an integral part of the natural genome.

Transposons are among the most common selfish elements.1 They consist essentially of a single enzyme that makes copies of the transposon and distributes them randomly throughout the genome, hence their alternative name ‚jumping genes‘. The evolutionary success of these jumping genes is impressive: half of the human genome consists of sequences that can be traced back to the activity of transposons.

Another variety of selfish element is widespread in bacteria: homing endonuclease genes.2 These genes also consist of only a single enzyme and can insert themselves precisely into certain DNA sequences. They spread rapidly and can even cross between different species of bacteria. The so-called homing gene drives were designed according to their model.

Gene drives, on the other hand, are selfish genetic elements created by humans. Their purpose goes far beyond their own propagation: they are intended to specifically exterminate living beings or to endow them with characteristics that serve human interests. Evolutionarily established mechanisms that protect the genetic material against selfish elements are likely to be ineffective. If gene drives become established in the genome, there is a risk of unforeseeable evolutionary changes in the manipulated organisms.

Austin Burt, Gene Drive Developer

CRISPR/Cas9 makes it possible

The realisation of Burt’s idea of converting selfish genetic elements for human purposes failed for a long time due to technical hurdles. This changed in 2012, when scientists Jennifer Doudna and Emanuelle Charpentier recognized the potential of CRISPR sequences.3 These short sections in the genome help bacteria to build up protection against viruses: The CRISPR sequence recognizes the intruder and activates enzymes that attack the virus and cut its genome.

The researchers were the first to recognize that the combination of CRISPR and Cas9 can be used to modify the genome of many organisms and introduce new segments into their DNA. It was the missing tool needed to turn Burt’s idea into reality4.

2015 was the first year in which the discovery of a functional CRISPR gene drive in fruit flies was published5. In the following year,s experiments on mosquitoes6 and mice7 were also successful. Researchers now suspect that almost any animal species could be manipulated by gene drives.

How does a CRISPR or homing gene drive work?

The most common variant of gene drive consists of three components: CRISPR/Cas9 gene scissors, a messenger molecule and a new or altered gene. The gene drive is first inserted into the genome of the target organism, e.g. a mouse, in the laboratory. This gene drive becomes active after fertilization of the egg cell and identifies a target sequence in the unmanipulated chromosome with the help of the messenger molecule. There, Cas9 induces a double-strand break.

Natural repair mechanisms in the damaged cell then attempt to repair the break using a template. The gene drive on the genetically modified chromosome itself serves as a template: it is highly likely to be copied completely and replace the previous gene on the chromosome that has not been manipulated. This targeted process is known as homing. It ultimately leads to all descendants of the organism inheriting a copy of the gene drive. The gene drive becomes active anew in every reproduction – including all subsequent generations – and theoretically only stops when the target sequence has disappeared from the entire population.