What are the Different Types of Gene Drive?

Gene Drive and Its Different Forms

Gene drive is loosely referred to as “a phenomenon whereby a particular heritable element biases inheritance in its favor, resulting in the gene becoming more prevalent in the population over successive generations” according to an article published in 2020 by the Proceedings of the National Academy of Sciences. Those involved in gene drive research have emphasized the need to clarify the terms pertaining to the technology to avoid the risk of hampering the field, confusing the public, and possibly losing a technology that may help solve some of the world’s most intractable problems in public health, conservation, and food security.

Dr. Alekos Simoni, Scientific Manager at the Polo Genomics, Genetics, Biology and a member of the Target Malaria consortium, further breaks down the definition of gene drive:

• It is a phenomenon of biased inheritance of a genetic element, or a gene, over the rest of the genome that leads to the increase of frequency over time.
• It is a genetic element, or the construct, that causes the process of biased inheritance.
• It is a tool to achieve a goal such as changing the population of target organisms.

According to Dr. Simoni, there are different types of gene drives, and here are some examples:

1. Homing-based gene drive. This is the most common type of gene drive that is used to target essential genes or drive a cargo. The method is based on the homing process, a natural phenomenon that occurs in a cell. A gene drive nuclease is inserted within its own recognition site of the homologous chromosome of the organism. When the DNA is expressed, it induces a DNA cleavage that will be repaired by the cell. Once repaired, the cell can make copies of the chromosome with the gene drive in it. This has been used to effectively control mosquito populations in laboratory conditions.
2. Sex distorter drive, or Y-drive. This is based on controlling the population by changing the balance between the sexes. In the case of mosquitoes, the population depends largely on the number of females. Thus, increasing the number of males by targeting the X-chromosome during male gametogenesis, generates male bias. This reduces the number of females that may lead to population suppression. It also decreases the ability of mosquitoes to transmit mosquito-borne diseases like malaria as only the female mosquitoes bite humans.
3. Split drive. This is similar to a homing-based gene drive, but its components are not linked together and are split into two loci. When together, one component spreads while the other is inherited in the Mendelian fashion causing the gene drive to decline over time. This method is effective for gene drives that are meant for limited targeted populations controlled in short periods of time as it is spatially limited and threshold dependent.
4. Maternal Effect Dominant Embryonic Arrest (MEDEA). This method is based on a toxin that is expressed from a maternal promoter and a zygotic antidote. When the gene drive spreads, it causes the death of the organism that does not have the construct since the toxin will kill any individual that does not contain the antidote. MEDEA is more challenging to construct due to its different components and it is difficult to transfer to other species as the toxin and antidote may work differently in different species….