Prime Editing — Genetically Modifying Humans?

What if I told you there was a way to enhance life here on earth. Sounds great? Well enter, genetic modification.

enetic modification has been on everybody’s mind for quite some time. Already we see it being used in things such as produce, to make more abundant yields, and in livestock, to increase size in cattle or other animals. However, has this been done in humans? Well, the short answer is yes — it has already been attempted. Twins in China named Lulu and Nana have had their DNA altered.

CRISPR-Cas9, a system used to insert, convert, delete, or combine DNA sequences, was used to modify DNA in a specific genome within the twins to form resistance to a serious disease, HIV. The Cas9 protein was implanted into the twins and used to cut and delete the undesirable sequence of DNA (CCR5) associated with HIV. Ultimately this aimed to provide them with resistance to the disease.

The news about the twins caused a lot of controversy. People deemed the experiment to be “ethically problematic” and one reason is that CRISPR, the technology used for this experiment, does not always produce accurate results.

“Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer,”

— Julian Savulescu

To be suitable for use on humans, genetic modification needs to have predictable outcomes. In this situation, Prime Editing may have been a better choice for genetic modification. The twins went through this procedure with no identifiable mishaps, yet may still face severe side effects. One side effect could be chromosomal translocation, which is the wrong arrangement of chromosomes, leading to dying cells causing weakness or in some cases death. Prime editing is another form of DNA editing, but uses a different procedure that leads to a more accurate system.

Prime editing, like CRISPR, is a multi-stage process that uses a biochemical machine with 3 (2 for CRISPR) main components: genetic scissors (Cas9 protein) and a GPS (PEG RNA), but unlike CRISPR, it also has an interpreter (The reverse transcriptase). The operation begins by the PEG RNA leading the complex to the correct DNA strand and sequence. Then, the Cas9 protein cuts a single strand so that it can be edited. At this stage in the process, CRISPR would be complete, but prime editing has reverse transcriptase and continues. Reverse transcriptase creates 2 strands of DNA, a strand that is the same as the one being edited and one with the edited sequence. The replicated strand binds to the nicked DNA so that the operation runs smoother. The edited strand is then later used to complete the DNA. The complex is led to the other side of the DNA and then the process repeats.

Figure 1: Prime Editing visual aid, slide reel. (Credit: Susanna M. Hamilton, Broad Institute Communications) https://www.broadinstitute.org/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells

Additionally, prime editing uses a far superior strand break process. CRISPR-based gene editing works by cutting both of the strands in DNA, which is called a double strand break (DSB). Prime editing uses a method that only breaks one of the strands in DNA while leaving the other strand intact, called a single strand break (SSB). This is superior because in keeping one strand intact, it makes for less of a chance to disorder the DNA. This results in a more reliable process taken into account that 2 strands will be harder to coordinate than a single one.

Figure 2: Susanna M. Hamilton, Broad Institute Communications Figure 3: “CRISPR: Cut and paste at the genome level” https://www.bsgct.org/crispr-cut-paste-genome-level/

As seen with the twins, genetic modification can be used to change a human genome. In this specific case, the gene CCR5 was deleted from a DNA sequence which studies show make mice smarter and also increase brain recovery in humans after a stroke. Scientists think that this can make people allegedly smarter. With CCR5 studies having shown some positive results in this past research, future projects may include designer babies and human enhancement (both physically and mentally). Potentially, this can be huge. It can help us eradicate many different genetic diseases or completely remove specific traits in plants or animals, like malaria in mosquitoes. Being able to read and write DNA at that level can even help us in creating artificial life. However, it could also be used inappropriately. Animals could be mutated in a way to be more feral and vicious, and gene editing in humans might breed a society of inequality.

CRISPR and Prime editing Pros and Cons

Both CRISPR and prime editing work well in their own respects. CRISPR being more efficient and Prime editing being more accurate. Despite this, the majority of genetic modification projects will favor accuracy over efficiency so prime editing is favorably better. Overall, prime editing is a good platform for genetic modification. However, like all things, it still has faults. Prime editing, among other platforms, still needs to undergo multiple tests and iterations before it would be deemed safe for human implementation. Moreover there are still many ethical questions around genetically modifying humans that need to be answered to ensure the responsible usage of this technology.

Article research and process

The process I took to get to the completion of this article can be found here.

Sources

Clinic, M. (Director). (2018, July 24). CRISPR Explained [Video file]. Retrieved July 30, 2020, from https://youtu.be/UKbrwPL3wXE

Dennis NormileNov. 26, 2., Lucy HicksJul. 31, 2., Charlotte HartleyJul. 30, 2., Charlotte HartleyJul. 29, 2., Charlotte HartleyJul. 24, 2., & Charlotte HartleyJul. 23, 2. (2018, November 27). CRISPR bombshell: Chinese researcher claims to have created gene-edited twins. Retrieved August 03, 2020, from https://www.sciencemag.org/news/2018/11/crispr-bombshell-chinese-researcher-claims-have-created-gene-edited-twins

Genome Editing. (2020, July 10). Retrieved July 29, 2020, from https://liugroup.us/research-overview/genome-editing/

KReme, C. (Director). (2019, December 05). Prime Editing Explained! [Video file]. Retrieved July 30, 2020, from https://youtu.be/vNcYhUTXzmY

Regalado, A. (2020, April 02). China’s CRISPR twins might have had their brains inadvertently enhanced. Retrieved July 29, 2020, from https://www.technologyreview.com/2019/02/21/137309/the-crispr-twins-had-their-brains-altered/

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