DNA DAY

 

Simone Cerrato ( classe 5E indirizzo Scienze Applicate) ha ricevuto una menzione d’onore, classificandosi nelle prime dieci posizioni, in seguito alla partecipazione all’European DNA day essay contest 2017 con l’elaborato in lingua inglese( di seguito riportato) sull’innovativa tecnica di editing genomico CRISPR/Cas9.

Complimenti a Simone!

 

Question: CRISPR/CAS9 is a powerful new technology  to change genetic material in all living material including humans, animals and plants. Explain how this technology works. Give your opinion about  problems and opportunities this technology should be used for, and what potential uses should not be allowed. Explain why you would make these choices.

 Author/Teachers: Simone Cerrato, Nadia Sibona, Marina Rista

Liceo Scientifico L.Cocito, Alba, Italy,

DNA Day link : http://www.dnaday.eu/winners2017.0.html

 

Abstract:

From the discovery of double elix DNA, the scientists have been focused on the goal of introducing site-specific changes in the genome of cells [1]. In the last decade the scientific research discovered a new easy way for genomic engineering, which could be used on animals, plants and humans. It’s called CRISPR (Clustered Regularly Interspaced Palindromic Repeats)/Cas9. This new genome engineering is reconsidering the genetic frontiers due to its simple application [2]. This new technology is an alternative to protein-based targeting ( TALEN and Zinc Finger). CRISPR/Cas9 is a sequence specific adaptive immune system discovered in prokaryotic. It is based on a group called: CRISPR array containing protospacers, which come from foreign DNA and are short sequences kept against future phage attack, separated by short palindromic repeats. In order to create CRISPR targeting RNA (crRNA) the array is transcribed forming the CRISPR array transcript (pre-crRNA). The creation of crRNA depends on the presence of trans activating RNA (tracrRNA). TracrRNA hybridized to short palindromic repeats and pre-crRNA with trancrRNA bind the cas9 nuclease, that becomes active and could cut off the DNA sequence complementary to crRNA. Each genomic target must be followed by a specific sequence on its 3’ end (PAM) that is critical for initial DNA binding. The cuts, depending on the spacers content and the co-expression of tracrRNA and pre-crRNA, are necessary to guide cas9 protein. Cas9 can induce precise cleavage inside the DNA. [3] [4]

CRISPR/Cas 9 is a new technology but it is still used to generate animals disease models for the basic research [5]. Furthermore we could use this to silence some proteins in animals, so we can obtain hypoallergenic products like eggs or milk . Moreover we can improve the disease resistance of some species or we could create transgenic animals that contain drug for some human disease, such cholesterol problems[5]. CRISPR/Cas9 application in plants will change the agricultural research [6] and it will be inserted in dairy culture system for cheese and yogurt production to protect the bacteria from phages attack [4]. CRISPR technologies can switch off some gene that control the rot of fruit. The most important goal is to use this CRISPR/Cas9 genetic engineering as a strategy for human therapies. It could be used to correct genetic mutations that cause inherited disorders, because the CRISPR/Cas9 system can do multiplex editing within a single mammalian genome [6] [7]. We can have targeted cleavage of mammalian chromosomes. Moreover the power of this technology could analyze gene functions in mammalian cells either the progression of cancer or genetic mutations.[6]

The results emphasize that RNA guided genome targeting in human cells is simple but there are some problems with this new engineering tool, because it is very easy to cut a part of a gene with CRISPR/Cas9 associated, but it is more difficult to insert the right gene. In the mammalian gene there is a risk using CRISPR with Cas9 enzyme, because we could only suppose to cut a specific portion of DNA sequence, but the Cas9 continues cutting off other parts of the genome DNA and it increases cancer risk. [8] Some eukaryotic viruses may express inhibitors such dsRNA-binding proteins that work against RNA silence machinery. Besides the viruses could mutate and change their own DNA and exceed the CRISPR spacers immune system. [9]

CRISPR/Cas9 was used for the first time on a patient with aggressive lung cancer as a part of clinical trial at the West China Hospital in Chengdu. It’s a big progress and it is the first entry of CRISPR onto the cancer fight. [10] But as we are using a very young technology, we have to wait other specific studies because a good target could be the power of editing some embryos and eradicate the genetic disease before the baby is born. [11]

In my opinion we need regulations in order to use CRISPR/Cas9, because we can’t use it to facilitate our life, if we don’t know the consequence that might happen if we modify too many animals in accordance with our desire. We don’t know the ecological consequences of releasing such animals with such features, although our first target is to prevent biodiversity. Furthermore there are serious concerns about using CRISPR/Cas9 system on humans. We don’t know the interaction between gene and environment or the random conseguences during years due the

hereditariness germline modifications. [12] Finally we can say that CRISPR/Cas9 gene therapy on humans needs more time.

References: citations

  1. The new frontier of genome editing engineering with CRISPR/Cas9, J.A.D, E.C., Science, 28 november 2014, vol. 346
  2. The power and possibilities of genome engeneering, J.M.P.; Science (in CRISPR Cas9: Engineering a Revolution In Gene Editing)(http://science.imirus.com/Mpowered/book/vscim14/i4/p6)
  3. CRISPR/Cas9 history, Addgene (https://www.addgene.org/crispr/reference/history/)
  4. CRISPR provides acquired resistance against viruses in prokaryotes, Science; 23 march 2007, vol. 315
  5. The CRISPR zoo, Nature, 10 march 2016, Vol. 531
  6. The new frontier of genome engineering with CRISPR-Cas9, Science, 28 november 2014, vol. 346
  7. Multiplex Genome Engineering Using CRISPR/Cas System, Science, 15 february 2013, Vol.339
  8. The gene editor CRISPR won’t fully fix sick people anytime soon. Here’s why By Jocelyn KaiserMay Science, latest news, 3 may 2016
  9. CRISPR-Cas9: Engineering a revolution in gene editing, Science, 26 september 2014, vol. 345
  10. CRISPR gene editing tested in a person, Nature, 24 november 2016, vol. 539
  11. Chinese scientists genetically modify human embryos, Nature news, 22 april 2015
  12. A prudent path forward for genomic engineering and germline gene modification, Science, 3 april 2015, Vol. 348

 

 

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