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Precision Medicine: Monkeys are Paving the Way for CRISPR

monkey and precision medicine on the right

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a prominent medical technology buzzword. It is widely in discussion and debate, for its innovation to precision medicine and gene-editing, and also its controversial implications on the management of diseases, and humanity. Scientists primarily use CRISPR to experiment on mice. But in 2014, researchers in China successfully engineered twin cynomolgus monkeys with targeted mutations. This is a critical milestone in CRISPR technology as it comes closer to more realistic research models of human diseases. Since then, monkeys are becoming instrumental in further research and experimentation using CRISPR. This is a Bold Idea that is paving the way to improving the way doctors treat patients using gene editing techniques.

Implanting the Seed, Gene Editing Technology

This technology is fairly new, and studies have not yet fully explored the potential side effects of gene-editing. A new team of Chinese researchers and scientists looked into CRISP-modified monkeys to find out if it causes severe side effects like cancer and unintended mutations., They assessed these monkeys to look for any unintentional mutations in their genomes. The study, however, is not yet peer-reviewed, but a version was published in bioRxiv in June 2018.

Researchers of the study designed a system to make the MCPH1, a gene expressed in the developmental stage of the fetal brain, inactive in rhesus macaques. Mutations in the MCPH1 gene cause abnormalities in the brain, effectively causing microcephaly in humans. They injected the system in 15 rhesus monkey zygotes, 13 of which developed into embryos. It is the next gestation phase where the cells begin mitosis. This was a preliminary experiment that allowed them to move on to testing on female rhesus monkeys.

The research team then injected the CRISPR-Cas9 system into 30 zygotes, and 24 of them developed normally. These 24 zygotes where then implanted into six surrogate female rhesus monkeys. Out of the six monkeys, two became pregnant. One gave birth to twins—one male, and one female that did not survive. The other female monkey gives birth via C-section to surviving triplets—two males and one female. All but one offspring, including the female monkey that died, consequently did not have any mutations that caused abnormalities.

how CRSPR works through gene editing technology infographic
Infographic Illustrating How CRISPR Works

Precision Medicine using CRISPR-Cas9

The CRISPR-Cas9 system consists of two critical molecules that create a change or mutation in the DNA. The enzyme Cas9 cuts two DNA strands at specific locations in the genome of a virus to add or remove a sequence. A guide RNA finds its target in the viral genome, and Cas9 cuts the strands, essentially disabling the virus. In the case of the rhesus monkeys, the team did not find MCPH1 genes in the DNA. This enabled the monkeys to develop normally. The team discovered that the CRISPR gene modification was effective on the test subjects.

The study then focused on looking for de novo mutations (DNM), or noninherited mutations. When Cas9 cuts the DNA, the DNA tries to repair itself as quickly as possible, which may result in connecting random strands. These random strand sequence could eventually manifest as diseases or mutations. When they inspected the sequence of the modified genomes, they discovered that it did not produce CRISPR-related DNMs. The monkeys did have some other DNMs, but these are expected to occur in any new generation of primates.

CRISPR Conclusion on Gene Editing Techniques

The researchers concluded that CRISPR-Cas9 is a relatively safe gene-editing technology for primates. Until this experiment, most scientists only worked with rodents or human cells. This study is the first to analyze CRISPR-modified genomes in non-human primates. There is only a 7% genetic difference between humans and rhesus monkeys, therefore scientists think that humans will respond well to this experiment. These gene editing techniques are paving the way for scientists to experiment for societal benefit.

a monochrome cartoon of a rhesus monkey wearing a cape posing as a superhero
Scientists are making progress in gene-editing technology and CRISPR with rhesus monkeys. What does this case mean for precision medicine and all humans?

With all its innovation on human genomics, CRISPR has its fair share of detractors. Some say it causes unintended genetic mutations and has far more negative ethical and moral implications than scientific advancement.

Those in the medical field see it as a breakthrough in precision medicine that will advance the quality of human life by permanently deleting diseases in human DNA. Because of the study with the rhesus monkeys, leaders in science consider CRISPR as a replicable and feasible study on human beings.

The first reported clinical trial on humans was in China in late 2016. The Chinese team did not disclose a lot of information because of doctor-patient confidentiality, but its leader, oncologist Lu You of Sichuan University said that the treatment was a success, and the patient was due for a second injection. It was also reported that clinical trials will start in the US and Europe almost simultaneously, but FDA put a pause on the US trials.

The world is anticipating more news about CRISPR, precision medicine, and their concrete applications and consequences on human life. And with laboratories and companies racing to conduct human trials, we may be hearing about conclusive reports sooner than expected.

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