CRISPR: A Powerful Gene Editing Tool
Feb 21, 2022 | Written By Sophia Mai
It is crazy to believe that something could directly modify or remove genes causing disease or change genes connected to traits, such as eye color and not only appearances but physical abilities and intellect. Although many of these traits have genetic and environmental factors, CRISPR can also raise ethical concerns about modifying specific characteristics of organisms or curing certain diseases. CRISPR-Cas9 allows for precise modifications to DNA that someday could prevent diseases such as cancer or create a drought-resistant crop faster, at a lower price, and higher accessibility compared with the gene-editing technology not even a decade ago. Interestingly enough, this genome editing system is derived from a defense system in bacteria. But to understand how CRISPR/Cas9 technology works, let’s talk about how some bacterial cells fight against foreign bodies, specifically viruses.
Bacterial Defense System:
CRISPR-Cas9 is adapted from a defense or immune system against viruses used by bacteria. Viruses, such as bacteriophages, attack bacteria by inserting their DNA and taking over bacteria systems to replicate themselves. Most bacteria will fail against virus attacks due to their poor defense systems, but some may survive because of an advantageous mutation during reproduction. Mutations are mistakes when replicating DNA that their offspring receive; however, mutations are not always beneficial. Most bacteria with mutations that do not benefit their survival will die and do not have the ability to pass the trait on to the next generation. When a bacteria survives, it saves a portion of the viral DNA into its own to create a ‘memory’ known as CRISPR arrays and retain a part of the DNA into its own. If the same virus attacks, the bacterium can use their DNA as a guide or instructions to create an RNA copy to target and compare genetic material in the cell. CRISPR uses many different proteins similar to Cas9 found in bacteria. When the DNA sequence is found that matches their RNA copy, a "Cas" enzyme cuts the DNA of the invader rendering it useless against the cell. Although immunity often is not transferred to offspring, bacteria acquire it through exposure to a virus. With CRISPR arrays the genetic material is encoded into the DNA, and the beneficial trait can be inherited by its offspring.
What is CRISPR/Cas9, and How Does It Work?:
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats which describes the regions of the bacteria DNA that alternate “spacers” and repeats. Palindromes are a sequence of letters that can be read forwards and backward like racecar or kayak. In genetic code, the palindromic repeats are small segments of DNA that have the same order of the bases in a DNA molecule, and each repeat is identical to the other.
Here is an example of one repeat.
Image from Bozeman Science (Youtube Video)
These bases, adenine(A), thymine(T), cytosine(C), and guanine(G), are the building blocks of DNA. They determine the genetic sequence of an organism that determines things like traits or instructions to code for proteins. The second component of the acronym is spacer DNA which are the CRISPR regions or copies of viral DNA that are unique and have different sequences between identical repeats. These are called CRISPR RNA (crRNA) and act as memories of viral infections. Outside of a bacterium, CRISPR is used for precise genetic modifications that allow scientists to change, add or remove segments of DNA in organisms with the use of Cas enzymes that can act like scissors and cut DNA at a specific region. Some of these proteins have been engineered to perform different tasks. Instead of cutting DNA, an enzyme could change a base in the DNA which often is enough to turn a trait or gene on or off. This ability could have future implications for single-gene diseases such as sickle cell anemia or cystic fibrosis caused by a single mutation in a gene, and as developments in CRISPR technology are made, there can be solutions to more complex diseases such as cancer.
There is a single mutation in a gene from a normal hemoglobin gene and a sickle cell gene.
With the use of this relatively new technology, numerous diseases could be cured, plants can be more resistant to drought and pests, and much more can be achieved that was not possible in the past through the implementation of CRISPR. While this technology is still relatively new and very powerful, there are consequences, precautions, and limitations to the use of gene editing. This technology raises ethical and safety concerns such as, is it right to genetically engineer human embryos without consent? Since there are possible changes to the human genome, what are the effects on the germline and future generations? Do the potential benefits of CRISPR outweigh the potential risks? Some also believe that gene editing will steer away from a tool for diseases and ailments and towards trait enhancements such as intellect or physical appearance. While gene editing on embryos and germline editing is banned in most countries, genome editing for preventing non-hereditary diseases is already in progress. There is still so much that is unknown about the possibilities and unintended consequences of gene editing, but are we willing to take that risk if it can enhance the lives of future generations?
Some additional links for more information!
Read about some of the First Human Trials using CRISPR.
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Bibliography
Arroyo-Olarte, Ruben D. et al. "Genome Editing In Bacteria: CRISPR-Cas And Beyond". Microorganisms, vol 9, no. 4, 2021, p. 844. MDPI AG, doi:10.3390/microorganisms9040844. Accessed 13 Feb 2022.
Vidyasagar, Aparna. et al. "What Is CRISPR?". Livescience.Com, 2021, www.livescience.com/58790-crispr-explained.html. Accessed 13 Feb 2022.
"What Are Genome Editing And CRISPR-Cas9?: Medlineplus Genetics". Medlineplus.Gov, 2020, medlineplus.gov/genetics/understanding/genomicresearch/genomeediting. Accessed 13 Feb 2022.
"What Are The Ethical Concerns Of Genome Editing?". Genome.Gov, 2022, www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns. Accessed 13 Feb 2022.
“What is CRISPR?” Youtube, uploaded by Bozeman Science, 18 February 2016, https://www.youtube.com/watch?v=MnYppmstxIs. Accessed 13 Feb 2022.