Generally, about 40% of diseases are caused by genetic defects. These diseases are known as genetic diseases. Due to the complexities of the human genome, scientists have been unable to completely unravel all of its mysteries. As such, one of the biggest challenges scientists have been faced with is providing a cure for genetic diseases and although several studies that attempt to develop solutions for these diseases have been conducted, none has been completely successful. The discovery of the CRISPR-Cas9 has formed a powerful gene-editing technology to correct defects in genes. In fact, most studies conducted during the past few decades have focused on CRISPR/Cas9 interaction to theorize therapies for genetic diseases. However, due to risks associated with the CRISPR/Cas9 technology, questions concerning its safety and ethicality still linger. Research conducted by a team of biologists at the University of California describes a novel approach using the CRISPR/Cas9 technology which may not only provide effective therapy for genetic diseases but also proves to be safer. Their strategy involves the use of natural DNA repair machinery to correct gene defects after cutting off the mutant DNA.
Using healthy gene variants to correct defective gene variants
Working on fruit flies, the scientists designed mutations on one component of a homologous chromosome in the fruit flies understudied. The chromosome used contained genes involved in the production of eye pigments. Fruit flies with mutated forms of the chromosome had characteristic white eyes, which slowly reverted to the original red color following the expression of CRISPR/Cas9 components by these flies. This reversal was attributed to the success of the cell’s DNA repair machinery in reversing the mutation using the functional DNA from the other chromosomal component of the homologous pair.
They then tested the novel system with Cas9 variants called nickases. However, unlike the Cas9 enzymes, which targeted the two DNA strands, nickases targeted just one strand of DNA. Additionally, reversal involving nickases recorded a greater repair success rate (about 50-70%) compared to reversal involving nickases which produced a 20-30% success rate.
The study was published on July 1 in the journal Science Advances.
In most cases, people suffering from genetic diseases bear the distinct mutations in both copies of genes inherited from their parents. This implies that oftentimes, a genetic mutation on one chromosome may have a healthy complementary sequence on the other chromosome. Using the approach described in this study, CRISPR/Cas9 technologies could be used to cut off the mutated genes and replace them with copies of replicated healthy DNA sequences obtained from that same individual. This will be of immense value in the treatment of conditions resulting from congenital enzyme deficiencies and other genetic diseases.
The method described by the team offers a safe, easy and effective approach to the treatment of genetic diseases. Although the results of this study are entirely corresponding to fruit flies, future applications in humans may offer a new fix for genetic diseases.