Gene Therapy, CRISPR/Cas9’s Applications in the Medical Field

Abstract

“CRISPR/Cas9-mediated glycolate oxidase disruption is an efficacious and safe treatment for primary hyperoxaluria type I” proposes, exactly as the title says, that the CRISPR/Cas9 system is a viable option for treating type 1 primary hyperoxaluria. It lays the groundwork for the proposal by mentioning several other genetic diseases that the CRISPR/Cas9 system has been used to treat, as well as the specifics of the gene defect that causes PH1, the AGXT gene. It states that en vivo correction is not a viable treatment option for the disease due to the lack of selective advantage for the modified cells and proposes a different approach. By targeting genes that express nonessential enzymes, the team believes that it can significantly reduces the oxalate buildup that causes the symptoms of the disease. This hypothesis is further confirmed by positive test results in mice. Human trials of GO silencing by this method were attempted in 2016, but there were some definite areas for improvement. While effective, the treatment currently needs to be administered several times to combat long term effects, and GO silencing using small molecules doesn’t block the enzyme completely, meaning that oxalate buildup still occurs, but a much slower rate, reducing patients’ risk of developing end stage renal disease (ESRD), an affliction of the kidneys that can be very fatal. The major questions for researchers hoping to take this topic further concern whether there is a method for more effectively inhibiting the glycolate oxidase enzyme while maintaining the standard of safety that the currently proposed procedure has?