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CRISPR's Ability to Cure Cystic Fibrosis

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Cystic Fibrosis is a common life-shortening autosomal recessive genetic disorder. This disorder is caused by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR). This CFTR gene provides instructions for making the CFTR protein which functions as a chloride conducting transmembrane channel. The channel transports chloride ions in and out of cells and by doing so, helps to control the movement of water in tissues, which is necessary for healthy thin and flowing mucus production. Out of the 1,000+ mutations in the CFTR gene related to cystic fibrosis. the most common mutation in the CFTR gene is called delta F508, causing a deletion of one amino acid at position 508 in the CFTR protein. This results in an abnormal channel which is broken down shortly after being made, meaning that it never makes it to the cell membrane so is unable to transport chloride ions. Due to no channel being present, mucus that is produced by cells becomes abnormally thick and sticky.

In the 1950s the average life expectancy for those suffering from cystic fibrosis was only a few months. While the average life expectancy has now increased to 40 years, this is due constant treatment such as airway clearance, aggressively treating infection and correcting nutrition deficits. Those suffering from cystic fibrosis have to constantly manage and treat their condition in many ways, this can include consuming up to 60 capsules daily just to help digest food, as well as up to four hours of airway clearance physiotherapy each day, use of inhalers to open airways and needing to consume high calorie, salt and fat diets. Those with cystic fibrosis are also encouraged not to socialise with one another due to the high risk of cross infection and exacerbation of lung conditions.

As CRISPR continues to make impacts in the science community, the gene-editing technique has become a desirable solution to many often life-threatening and incurable genetic conditions. The following will investigate what CRISPR is, what it can do and whether it can cure cystic fibrosis.

Clusters of regularly interspaced palindromic repeats, commonly known as CRISPR or CRISPR-Cas9, is a specialised region of DNA that contains nucleotide repeats and spacers. These repeated nucleotide sequences are distributed throughout a CRISPR location and the spacers are interspersed among the nucleotide repeats. CRISPR works by taking the spacers from (in the case of bacteria) viruses that previously attacked the organism and uses these so that in the future the bacteria can recognise the virus and fight it off. “Once a spacer is incorporated and the virus attacks again, a portion of the CRISPR is transcribed and processed into CRISPR RNA, or crRNA”. The Cas9 protein is then guided by the crRNA and tracrRNA strands to the site, where Cas9 makes its cut.

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Through Martin Jinek and his colleagues research, they were able to simplify the process by fusing crRNA and tracrRNA to create a guide RNA, meaning that in order to edit DNA you only need to design a sequence of 20 base pairs that match the gene that you want to edit and the Cas9 protein will cut it there. However it is important to make sure the sequence is not found anywhere else in the genome. Once a cut is made, the cell will naturally repair itself by either non-homologous end joining, which involves gluing the two cuts back together or by filling the gap with a sequence of nucleotides, these can be made and inserted artificially, allowing for rewriting of any gene.

Giulia Maule and her team in 2019 were able to show “efficient repair and complete functional recovery of the CFTR channel” through their highly precise genetic repair strategy in patient carrying the 3272-26A>G or 3849+10kbC>T mutations. Also in Gerald Schwank and his colleagues in 2013 were able to successfully “correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients”. These genes however, were derived from adult stem cells with a single-gene hereditary defect. While CRISPR has been shown to work in adults, due to the editing of somatic cells, the edited gene will not be passed on to future generations. When editing reproductive cells or embryos however, they will pass these edits on to future generations, but this does raise ethical concerns.

In 2018 He Jiankui edited twin human embryos with CRISPR for the stated purpose of disabling the CCR5 gene, which allows HIV to invade cells. While this may seem revolutionary, other countries are lagging behind China for good reason. The process to even get clearance for a trials using CRISPR is far more rigorous and require thorough evidence to prove that the trial will not cause unforeseen adverse consequences.

CRISPRs ability to edit genes and allow scientist to even add their own sequences to genes is truly phenomenal and as shown in Giulia Maule’s and Gerald Schwank’s studies, CRISPR can repair and correct CFTR mutations, meaning that it can ‘cure’ cystic fibrosis. But neither of these studies were actually implemented in a human but rather in the patients cultured cells. So yes it can cure cystic fibrosis from what has been seen in research, but further testing will need to be done for a precise and ethical cure.

Works Sited

  1. https://www.sciencedirect.com/science/article/pii/S0140673616005766
  2. https://ghr.nlm.nih.gov/gene/CFTR#conditions
  3. https://search.proquest.com/docview/199645409?accountid=13380&rfr_id=info%3Axri%2Fsid%3Aprimo
  4. https://search.proquest.com/docview/1771324648?accountid=13380&rfr_id=info%3Axri%2Fsid%3Aprimo
  5. https://www.cysticfibrosis.org.au/about-cf/what-is-cf
  6. https://www.livescience.com/58790-crispr-explained.html

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CRISPR’s Ability to Cure Cystic Fibrosis. (2022, August 25). Edubirdie. Retrieved February 8, 2023, from https://edubirdie.com/examples/crisprs-ability-to-cure-cystic-fibrosis/
“CRISPR’s Ability to Cure Cystic Fibrosis.” Edubirdie, 25 Aug. 2022, edubirdie.com/examples/crisprs-ability-to-cure-cystic-fibrosis/
CRISPR’s Ability to Cure Cystic Fibrosis. [online]. Available at: <https://edubirdie.com/examples/crisprs-ability-to-cure-cystic-fibrosis/> [Accessed 8 Feb. 2023].
CRISPR’s Ability to Cure Cystic Fibrosis [Internet]. Edubirdie. 2022 Aug 25 [cited 2023 Feb 8]. Available from: https://edubirdie.com/examples/crisprs-ability-to-cure-cystic-fibrosis/
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