What is CRISPR? A Primer

CRISPR is known as a cutting-edge tool for gene editing. Would you be surprised to learn that  that CRISPR originally evolved within single-celled organisms such as bacteria, as their own immune response to viruses? When viruses attack a bacterial cell, they inject their genome—their own viral DNA—into the cell. The bacterial cell, in turn, responds by deploying CRISPR: a scissor-like enzyme called CRISPR-associated protein, or Cas, hooked to a strand of RNA.3 The RNA recognizes the viral DNA, and Cas completely inactivates the targeted gene by making a precise cut in the gene, disabling the viral attack.1

CRISPR is an acronym for “clustered regularly interspaced short palindromic repeats,” which refers to the unique gene organization of bacteria and other microorganisms with short, partially palindromic repeated DNA sequences.2  Since its discovery in bacteria in 2012, scientists have been working in the lab to reproduce the CRISPR method to target plant or animal DNA, rather than viral DNA. CRISPR has the potential to “knock out” specific, targeted genes in plant, animal, or even human cells and, if a strand of DNA coding for a new gene is added, CRISPR can potentially provide a patch in the new gene between the severed ends. If it works, it would actually be fairly simple to design—all a researcher needs is a piece of RNA that can lock on to the targeted gene, attach it to a Cas enzyme, like Cas9, and you have a precision DNA editing tool.1

CRISPR editing technology has the greatest medical potential in humans in utero, to edit genes before birth and prevent the transmission of deadly genetic diseases like Tay-Sachs. Once a person is born with a disease like Tay-Sachs or Huntington’s disease, it’s much more difficult to use CRISPR to treat it.3 Gene editing is also being tested to treat conditions like cancer, blindness, sickle cell, thalassemia, and liver disease—among others.3,4

CRISPR has potentially broad applications that could impact allografts and human tissue engineering. It’s already being used to edit the genomes of mosquitoes, in the hopes of being able to prevent their ability to carry infectious diseases like Zika.3 And CRISPR/Cas is being applied directly within the field of tissue engineering, where it has been used to modify the expression of bone morphogenetic proteins (BMP) improve the osteogenic potential of adipose-derived stem cells (ASC).5

Another application of CRISPR is to edit induced pluripotent stem cell (iPSC) genomes to create special cell lines for use in tissue engineering.5 As techniques are developed to aid in homing and differentiation of stem cells, these customized iPSCs  may allow for the creation of multi-layered tissue scaffolds; cardiovascular grafts, whole organs, and other complex tissues could then be created.

For now, however, medical applications are confined to laboratories.1 Two recent studies have raised concerns that edited cells, designed to treat disease, might trigger cancer, demonstrating the need for further research and refinement before the technique is deployed. Experts describe the cancer risk as “plausible,” but not a “deal-breaker.”4  Considering the potential benefits to humankind, we’ll be staying tuned as the research evolves.


[1] Richter, V. (2016, 18 April). What is CRISPR and what does it mean for genetics? COSMOS: The science of everything. Retrieved from: https://cosmosmagazine.com/biology/what-crispr-and-what-does-it-mean-genetics

[2] Pak, E. (2014). CRISPR: A game-changing genetic engineering technique. Harvard: Science in the News. Retrieved from: http://sitn.hms.harvard.edu/flash/2014/crispr-a-game-changing-genetic-engineering-technique/

[3] Delviscio, J. (2018, April 4). How CRISPR works, explained in two minutes. STAT. Retrieved from: https://www.statnews.com/2018/04/04/how-crispr-works-visualized/

[4] Begley, Sharon. (2018, June 12). CRISPR-Edited cells linked to cancer risk in 2 studies. Scientific American. Retrieved from: https://www.scientificamerican.com/article/crispr-edited-cells-linked-to-cancer-risk-in-2-studies/

[5] Pulgarin, D. A. V., Nyber, W. A., Espiinosa, A. (2017, July). CRISPR/Cas systems in tissue engineering: A succinct overview of current use and future opportunities. Current Trends in Biomedical Engineering and Biosciences, 5(4), 001-004. doi:10.19080/CTBEB.2017.05.555670