How does homing work?

Category: Gene Drive Mechanisms

Homing functions within a germline cell that will produce a sperm or an egg. It can be initiated by naturally occurring genes (homing endonuclease genes) or synthetic mimics of such genes, which code for an enzyme (endonuclease) that will recognize and cut a specific DNA sequence. In a cell that has one chromosome containing the endonuclease gene and one that doesn’t, the enzyme will create a break at the specified DNA sequence in the chromosome that doesn’t. Natural cellular repair processes result in the endonuclease gene being copied into the repaired chromosome. This very efficient creation of germline cells that have two copies of the endonuclease gene (and any associated genes, together termed the endonuclease construct) creates strong drive, because the genes now will be inherited by progeny that receive either chromosome and the copying process will continue to be repeated in those progeny. This results in preferential inheritance of the gene in subsequent generations.

The endonuclease construct can be targeted to a specific place on the opposite chromosome by adding a piece of nucleic acid that serves as a “guide.” The endonuclease construct also can be engineered to have additional functions besides producing the DNA-cutting enzyme. This might introduce an intended new characteristic (trait) into the organism. For example, a new characteristic could result from inactivation of the targeted gene into which the endonuclease construct is copied. Or alternatively, another gene coding for a new characteristic can be coupled to the endonuclease gene so that it is carried as cargo and copied into the opposite chromosome along with the endonuclease gene. This construct might also contain a genetic switch that can turn the other genes on and off at the right time in the cell cycle. With gene drive, the new characteristic can spread by mating within an interbreeding population.

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