Along with the passage of time, genetic modification (engineering), a process to modify genetic materials of organisms, is one of the most important technologies that will lead our future generations. This technology has numerous advantages in various fields: medicine, biological engineering, environmental science, etc. In recent times, after the Covid-19 worldwide pandemic, the importance of this technology becomes more spotlighted because the production of vaccines for this virus is completely based on genetic editing. Especially, mRNA vaccines that Moderna and Pfizer mainly have produced are one of the instances of the genetic materials. In addition, by modifying certain parts of the genome, humans can generate some plants that are resistant to certain viruses or can be supplied in a large quantity, resulting in a solution to the global food crisis. Then, thanks to genetic scissors, all of them are possible in the modern-day, and it is time to dig into these scissors.
History of genetic scissors
The first generation of the tools is called “Zinc Finger”. In 1980, it is found in a part of an African clawed frog’s body. This scissor mainly comprises certain Zinc molecules and a restriction enzyme, called “FokI”. This artificial endonuclease would bind to certain genetic sequences, cut these parts of genetic materials, and regulate the gene expression of these parts. Since it was the first genetic scissors, many scientists issued this technology. However, it also has many restrictions. Firstly, it was too difficult to construct this tool. Since it contains a very complicated protein structure, many scientists cannot flexibly use these scissors. Also, it can read only three to six nucleotides, making it very inefficient to apply in a lot of fields in our life. However, it is true that it was an incredible and shocking discovery in various fields from biology to medicine.
To overcome several restrictions and attempt further development on our genetic technology, the scientists made the second generation of the genetic scissors, called “TALENS”. This manmade endonuclease also utilizes the FokI restriction enzyme with a combination of transcription activator-like effector proteins found in a pathogen called “Xanthomonas”. It has a similar mechanism to that of the Zinc finger, but it has several noticeable improvements on the overall process. At first, while the Zinc finger reads a very limited number of nucleotides as a unit, this new technology can read 10 or 15 nucleotides as a base. Additionally, it can cut DNA much more precisely than Zinc finger does. However, despite these significant benefits, there are some risks. First of all, it is more difficult to construct these scissors. Since these scissors have a much more complex entire protein structure, humans need to spend a lot of time and money, making it inefficient. Therefore, it was nearly impossible to apply in various fields as an industrial level.
Nowadays, scientists and engineers realized these practical restrictions on this technology, so they have further developed these scissors. Finally, they can make other genetic scissors, called “CRISPR-CAS9” as a third generation. Unlike the first and second genetic scissors, this technology uses another endonuclease, known as “Cas9”. Then, this technique is a combination of Cas9 endonuclease and guide RNA (gRNA). This guide RNA has a base consisting of RNA nucleotides that are complementary to the targeted DNA sequences. Then, this RNA would find and bind to the targeted genes that correspond to the RNA sequences. Lastly, Cas9 endonuclease would cut this part of genes. Surprisingly, this guide RNA technology is a key method in this model because it overcomes the original problems in terms of the flexibility of genetic scissors. Also, it has a very simple protein structure. Therefore, by changing the RNA base with a range of 19 bases, humans can easily produce very various scissors that can be utilized in many fields. Also, there is no risk in terms of costs and time durations to construct new ones. As a result, many applications exist. For example, as therapeutic implications, humans can treat sickle cell disease, Parkinson's disease, and HIV by cutting the origin of the disease. However, it is true that a limitation still exists. For instance, it sometimes cut DNA outside of the targeted genes, called “off-target” editing, resulting in substantial genetic mutation. Although there are not enough amounts of clear implications of this scissor with several restrictions because it is developed in the near past, many professionals do not deny that it is a key factor to change our future biotechnology and medical technology.
Future
As many scientists have made and developed genetic modification, many scientists expect that the next generation will be introduced in the near future, called “base pair changes”. Briefly, the mechanism of this method is mainly to read targeted DNA sequences without cutting this part of DNA, leading to fewer errors after cutting DNA like genetic mutation. Therefore, major scientists argue that the focus of our future in genetic modification is precision in a single genetic material.
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