5/31/2022 - Technology and Innovation

The technology of the future: CRISPR CASH

By Sahira Janeir Garazatúa

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It is known that DNA is the molecule that stores genetic information, each of the functions and characteristics that distinguish an individual, and that is composed of 4 nucleotides: adenine (A), cytosine (C), guanine (G) and thymine (T). The only combination of these four letters along the DNA generates a code capable of deciphering, and the knowledgeable being of this gives you the power to understand how it works and take it to the next step: that of manipulating.

As an engineer in systems develops codes from a binary (0.1) system for machines to perform different functions, encode DNA from a four-letter system (A, C, G and T) allows a living organism to act based on the way it codified and programed it. But through which mechanisms can the DNA of an organism be changed? To do this, technologies called “molecular injections” are needed, which can cut this DNA into specific regions, either to remove a fragment or to introduce a new one. In principle, the technologies called zinc finger nucleasas and TALEN (nucleases transcription activator type effectors) were used but were finally replaced by the CRISPR-Cas system due to the ease of its synthesis, the market price, its effectiveness and accuracy in DNA cuts.

What's your use?

As comments Claes Gustafsson, president of the Nobel Committee on Chemistry, “There is enormous power in this genetic tool, which affects us all. It not only revolutionized basic science, but also gave rise to innovative cultures and will give rise to new innovative medical treatments. ”, this technology is very versatile and can be used with multiple goals: in basic science to create models that facilitate study and in applied science in different fields:

  • In Biotechnology Modified pigs were developed for organ transplantation with the absence of certain genes to prevent immunological rejection, cows capable of synthesizing pharmaceutical products in milk, managed to reduce the population number of species that cause endemic diseases such as mosquitoes with dengue by modifying them and cando them infertility.
  • In Biotechnology Modified plants of commercial interest resistant to climate conditions, fertilizers, were developed plant vaccines and created flowers with desired pigmentation.
  • In Biotechnology of microorganisms For example, genomes of bacteria of interest in the industry were modified to save processes, or to biodiesel production.
  • They are also being developed mechanisms to cure diseases, as gene therapy in which one tries to eliminate in patients genes that cause disease that suffer or exchange a mutation by the correct sequence, or even insert a gene to increase its expression, in the case of insulin in diabetic patients, for example. On the other hand, there are antibiotic-resistant bacterial infections, and a possible way to cope with this would generate genetically modified viruses to specifically attack the type of bacteria that generates the infection.

Your discovery

To the surprise of all, the CRISPR-Cas system is not as new as one could think, it was discovered in bacterial genomes and archea for more than three decades in 1987 by biologist Yoshizumi Ishino. This researcher observed in the genome of these microorganisms the presence of repeated DNA sequences (CRISPR sequences) interrupted by a spaciating DNA. But what was this system really for? After several hypotheses, it was discovered that when a virus infected the bacteria or archea; the system functioned as a guide to the viral genome and protein molecular scissors cut it by eliminating the virus. Therefore, this system acted as a defense mechanism, or as a sort of antiviral immune system.

In which consists CRISPR-Cas9

Although there are six types of CRISPR-Cas systems, the best characterized and used in genetic editing is type II (CRISPR-Cas9). It basically consists of a DNA region consisting of two types of sequences: repetitive sequences and between each repetition, a space sequence that is complementary to the virus sequence, i.e., that can adhere to a specific region of the virus. Each repetitive sequence + a spacing sequence transscribes the RNA (Rioonucleic Acid) forming a _ which in turn matches with another RNA (Trans-ARN) forming a ARNguia. This complex is directed to a specific region of the virus thanks to the spacing sequence and a protein, the caspase 9 (Cas9) works as scissors cleaching the genome of the virus only if this region is adjacent to short sequences called “PAMs”.

Following this discovery, in 2012 the researchers Emmanuelle Charpentier and Jennifer A. Doudna They found a potential use to the CRISPR-Cas9 (type II) system adapting it as a very important technology for the field of gene editing, which meant a nobel prize of chemistry shared in 2020. They were able to demonstrate that by designing an ARNguia aimed at a region of interest, caspase 9 could cut the DNA of this region by eliminating the functionality of this fragment, and that, if it also applies an extra DNA sequence that works as a mold, fragments can be added with information, modifying the DNA of any organism.

Currently, variants of CRISPR-cas9 have been developed that do not edit the DNA sequence itself, but are used as guides for a specific region and alter the expression of the gene or genes present in this region (activate or disable), or fuse proteins for this region as for example a fluorescent protein to locate in which genome region this specific sequence is present. Where else do we imagine this technology could come from?

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sahira janeir

Sahira Janeir Garazatúa

Hi, I'm Sahira, Biotechnologist Biomedical! I studied in Buenos Aires where I focused on epigenetics and reproduction, but now I find myself in Spain developing cell therapy and neuronal regeneration of the spinal cord, and combining AI for early detection of diseases. In addition, the CDTM Technology Management, Valencia-Munich study, which develops innovative digital products and solutions for companies such as Lufthansa and S2group.

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