Research from the California National Primate Research Center (CNPRC) is paving the way for future studies where the possibility of birthing gene-edited monkeys that can serve as models for new therapies is greatly increased. CNPRC scientists efficiently used CRISPR/Cas9 technology to modify the genes of rhesus macaque embryos.

Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) is essentially a DNA segment that scientists can manipulate using a system known as CRISPR/Cas9 to edit the genes within organisms. CRISPR/Cas9 seeks and targets specific genes in organisms that are linked to diseases by utilizing a single strand of RNA as a guide to target specific genes for editing.

But the technology can also be imprecise – causing off-target effects to genes that were not intended to be targeted.

“One of the problems with the CRISPR/Cas9 approach is that you have to target the gene,” said Catherine VandeVoort, the core scientist at the CNPRC who collaborated with Keith Latham of Michigan State University and Dr. Daniel Bauer at Harvard Medical School for the study. Latham designed the CRISPR/CAS9 system used in the CNPRC project. “When you have a very short (gene) sequence that you are targeting, it may show up in different places, in another part of the DNA strand instead of where you intend. It can cause off-target effects.”

While rodent-based research models are good for studying diseases in the early stages of research, rodents differ from humans in many anatomical and physiological ways. Alternatively, nonhuman primates share many similarities to humans.

However, while the monkey research model is better for studying human disease, it is much costlier than rodent-based models. “In monkeys, we can’t afford any off-target effects and so we asked ourselves, ‘How can we make this more efficient?’” VandeVoort said.

To minimize the risk of the off-target effects, the study used a two-pronged approach to increase the efficiency of the CRISPR/Cas9 targeting.

The scientists successfully edited the genes of the monkey embryos with 85 percent efficiency. That study demonstrated the first time in the U.S. that this method could effectively be used in monkey embryos. VandeVoort said the embryos used in the study were not implanted in recipient female monkeys, but that a future study will transplant the embryos with a goal of creating a gene-edited monkey.

Reviewed August 2019

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Photo credit: Kathy West for the California National Primate Research Center