The history of CRISPR

How exactly did a prokaryotic defense mechanism system, which was developed to protect the host against phages and viruses, become one of the most widely used genome editing tools?

Given the young age of CRISPR-Cas genome editing tools, it may be surprising that early experiments on CRISPR took place in the late 1980s, when several researchers independently observed DNA repeats in the bacterial and archaeal genomes. More than a decade later, thanks to the increased number of publicly available prokaryotic genomes, scientists kept consistently finding these repeats, and the term “CRISPR” was eventually proposed by Jansen, et al. in 2002, and it was generally accepted in the scientific community.

A few years later, in 2005, several independent research groups noticed a clear resemblance of sequences separating identical CRISPR repeats (spacer regions of CRISPRs) to sequences of bacteriophages, archaeal viruses, and plasmids, which gave us the first hint about the biological function of CRISPR. These research groups suggested that CRISPR sequences function as a biological defense system similar to the eukaryotic RNA interference (RNAi) system that acts to protect the host cells against phages and plasmids.

At the same time, researchers confirmed that several genes initially thought to code for DNA repair proteins were actually CRISPR-associated, which led to the logical name of cas (CRISPR-associated) genes. Further genomic analyses suggested that CRISPR and cas proteins work in concert and constitute an adaptive immune system protecting prokaryotic cells against viruses and plasmids.

So far, we have established what CRISPR is and have briefly traced the history of main discoveries and concepts. Now, it is time to talk about why these discoveries were so groundbreaking that they led to a genome editing revolution in biology and prompted Science to name CRISPR the Breakthrough of the Year in 2015.

Several reasons explain why CRISPR-Cas9 technology is so widely and successfully used:

• CRISPR-Cas9-based machinery is fast, efficient, and easy to manipulate
• Cas proteins are affordable, transferable, and specific
• RNA guides are programmable, and this overall flexibility gives scientists the opportunity to use CRISPR-based technology in a variety of research applications, some of which will be mentioned here

CRISPR sequences have been successfully used as genetic markers for species typing of important-to-human-health microorganisms, including Mycobacterium tuberculosis, Yersinia pestis, Salmonella spp., and Corynebacterium diphtheriae. Even though CRISPR-Cas systems originally played a defensive role by protecting bacterial genomes against phages, they can be reprogrammed for self-targeting, which would result in bacterial death. Given the wide use of these systems in various pathogens, including Salmonella, Escherichia coli, and Clostridium difficile, it is possible to specifically target and eliminate these pathogenic microbes. The same principle of targeting specific microbes can be used to modify an organism’s microbiome to promote beneficial species and remove the harmful ones.

Another important CRISPR application derives from the fact that it can be easily used to edit the genomic content of model organisms that are commercially utilized in the food biomanufacturing, agricultural, and pharmaceutical industries, among others. For example, broad-spectrum phage resistance has significantly increased in model bacterial strains utilized in dairy industry.

CRISPR-Cas discovery itself has significantly contributed to our understanding of fundamental biology. In addition, the importance of genetic engineering tools that emerged as a result of this discovery is so high, parallels can be drawn between the CRISPR-Cas9 genome editing technology and PCR, which is one of the most groundbreaking discoveries in the field of biology and a prominent example of disruptive science.

In this post, we have barely scratched the surface of what CRISPR-Cas9 technology has to offer. Laboratories all over the world are leveraging both scientific knowledge gained from the latest CRISPR experiments, and the power of state-of-the-art equipment and reagents produced by leaders in the field, including IDT. More CRISPR applications are on their way and it’s safe to assume that this research field will be providing us with cutting-edge discoveries in the years to come.