New Mutation Technique Could Expedite Genetic Manipulation

Biology researchers at UCSD recently created a new method, mutagenic chain reaction, for converting heterozygous mutations to homozygous mutations in a chain reaction.

This discovery is a leading breakthrough as it is an improvement in the current technology and contradicts the laws of Mendelian genetics. According to Mendelian genetics, an individual has received one copy of most genes from the mother and the other copy of most genes from the father. In the case that an individual inherits a copy of a mutated gene and a copy of a normal gene, then the individual is phenotypically normal but is a carrier of the condition. However, when an individual has two copies of a mutated gene, they exhibit the condition. 

The researchers, Professor Ethan Bier and  Ph.D. student Valentino Gantz, recently published their findings in Science, detailing mutagenic chain reaction. 

Bier explained that, in the past few years, there has been a wave in genome manipulation where it is now possible to manipulate and change the genome of an organism.  

“It is now routine to generate virtually any change in the genome of an organism of choice at will,” Bier said in a press release.

The Clustered Regularly Interspaced Short Palindromic Repeats is an example of this and was used to eliminate HIV from infested cells by the Salk Institute. 

However, lead author Gantz said that the mutagenic chain reaction is far more efficient than the Cas9/CRISPR system since the CRISPR technology has to be executed manually on each sequence, and the mutagenic chain reaction is simply able to duplicate the mutation from the chromosome and quickly spread it. 

“MCR is remarkably active in all cells of the body with one result being that such mutations are transmitted to offspring via the germline with 95-percent efficiency,” Gantz said in the press release. “Thus, nearly all gametes of an MCR individual carry the mutation in contrast to a typical mutant carrier in which only half of the reproductive cells are mutant.” 

Bier and Gantz performed the experiment on the fruit fly Drosophilia melanogaster where they discovered that a mutation generated on one copy of the chromosome quickly carried over to the other corresponding chromosome resulting in both copies of the gene having the mutation. This new technology can facilitate further research into genetic engineering and genome manipulation and has the potential to eradicate diseases, such as malaria, and even fix HIV-infected cells or cancer cells. 

Scientists, such as George Church, a prominent geneticist from Harvard, criticize the study for being a “step too far.” Church and other prominent geneticists discussed how the technology would allow researchers to edit genes in the human germline and could result in the spread of deleterious mutations to the rest of the population.

This study was funded by two grants, and a patent has been filed by the UCSD Technology Transfer Office to license the new technology.