CRISPR to Edit Gene: Saviour or Disruptor?

The 2020 Nobel Prize in Chemistry has made CRISPR an instant hit. So how did CRISPR get preferred by the committee to receive this fabulous prize? This article will introduce the details of CRISPR technology.

First of all, it is known that CRISPR technology is a technology for editing genes. A gene carries the genetic information of an organism and is a precise set of codes storing the race, blood type, conception, growth, and apoptosis of life. However, gene editing is not an easy task, one of the reasons being that there are many genes and no label to tell us which gene corresponds to which trait. But CRISPR, this gene editing technology, ignores the challenges posed by genes and enables gene editing by adding, deleting or altering DNA at specific locations. In the last decade, there has been an explosion in the amount of research revolving around CRISPR technology.

CRISPR is from bacteria

CRISPR stands for clusters of regularly interspaced short palindromic repeats, a specific region of DNA composed of genomic targeting sequences (spacer) and nucleotide (part of the DNA backbone) repeats, which is part of the bacterial immune system, and thus was first adapted from bacteria.

To defend against foreign viral infections, bacteria cut and destroy the DNA of invading viruses. When bacteria survive a viral infection, they retain a portion of the viral DNA to record the "criminal history" of these "culprits". These "souvenirs" from the invading virus DNA are stored in spacers in CRISPR. The next time the same virus invades, the bacteria can quickly identify the invading virus and destroy the viral DNA.

How does the CRISPR system work?

The CRISPR-Cas9 mechanism has two main parts: 1) the Cas9 protein, which acts as scissors, and 2) a custom-designable RNA guide sequence that acts as a guide. To edit a gene, one has to use scissors to remove the unwanted part first, while the location of the cut requires the guide.

The Cas9 protein "reads" the host DNA through a guide RNA to find the target gene. When the guide RNA pairs with the target sequence, it usually triggers the Cas9 protein's own cleavage mechanism, which cuts the nucleotide bonds of the target gene.

After a cleavage occurs, the cell's own DNA repair mechanism glues the cleaved nucleotides back together to complete post-shear repair by a method called non-homologous end joining. This approach is relatively rapid, but usually results in errors or imperfect repair, making the sequence no longer readable and translatable by the cell, causing it to become inactivated. This is known as gene knockout.

If the DNA repair described above is skillfully exploited, it can be used to edit or insert a new genetic code. This process is called gene knock in. In a gene knock in application, the CRISPR/Cas9 system is introduced with the DNA template and inserted at a precise location in the genome. This process then requires the initiation of another DNA repair mechanism, homology-directed repair, to complete the process.

The controversial CRISPR technology

The ability of CRISPR technology to precisely edit genes has made it a useful tool in a variety of fields. However, as is the case of other technologies, CRISPR's ability to modify genes brings with it the possibility and risk of unethical applications. Many researchers and bioethicists are concerned that CRISPR-Cas9 technology will open Pandora's Box as the development of this technology is far from flawless. In particular, CRISPR technology could cause unpredictable catastrophes when applied to editing human genes.

The human genome is an elaborate and complex system. The same gene may be associated with multiple functions, and some functions may be hitherto unknown to us. Thus, editing a single gene could lead to unexpected genetic changes that could even transform future generations and the entire human race. Therefore, scientists are calling for a moratorium on the application of CRISPR technology to human germ cells, thus to give scientists and bioethicists more time to assess and analyze the potential risks of the technology.