ses V and VI are rare and affect very few people. For the most part, these mutations decrease the CFTR gene’ s effectiveness, leading to mucus clogging the pancreas( which means digestive enzymes that break down food aren’ t released) and the lungs( which means bacteria cause infections and mucus inhibits breathing).
As of now, there are several treatments available for treating cystic fibrosis. These range from lumacaftor( enhances the folding ability of protein) to ivacaftor( opens the ion channels of the CFTR gene). These treatments-- along with several others-- have increasingly prolonged the lives of CF patients over the years to a median age of forty; in the 1950’ s the expected CF patient lifespan was below ten years of age. Despite these advancements, there remain limitations. For example, both lumacaftor and ivacaftor result in minimal lungcapacity improvement, one of the most prominent concerns among CF patients.
Furthermore, while these treatments do target specific mutations, CF patients still face necessary dayto-day treatments. Every day, they must use a highfrequency chest wall oscillation device( known as the Vest) for several hours; the Vest sends vibrations through the chest loosening mucus. CF patients must also consume around ten pancreatic enzymes( by pill) at each pill that assist the digestive tract in assimilating nutrients from food.
This is where CRISPR-Cas9 comes into play. CRISPR-Cas9 is [ insert CRISPR summary ]
In the case of Cystic Fibrosis, CRISPR-Cas9 targets and corrects the mutated F508del-CFTR gene( F508del-CFTR refers to the name of the mutation in that specific gene). The inputted CRISPR sequences form CRISPR ribonucleic acid( crRNA) molecules, which eventually target the F508del-CFTR mutation. More specifically, peptide nucleic acids( PNAs) attach to DNA close to the mutation and essentially trigger repairment within the DNA. A study conducted by Gerald Schwank and Bon-Kyoung Koo exemplified how CRISPR-Cas9 could be inputted into CF patients.
To test the possible benefits of CRISPR-Cas9 on CF patients, the two scientists, both from the University Medical Center Utrecht, conducted a study to correct the F508del-CFTR mutation in adult stem cells. First off, cells from two CF patients were cultured into organoids( a miniature organ). Then, the organoids were encoded with a wild-type CFTR mutated gene as well as with CRISPR-Cas9. The encoded CRISPR-Cas9 genetically repaired the mutated gene, with only one mutation being off-target, meaning a low probability of a phenotypic consequence( and therefore a low risk).
This proved considerable promise for CRISPR- Cas9 correcting CF mutations, but the study still failed to address CF lung-related pathophysiology. CRISPR- Cas9 is still in its early stages of assisting in the repair of mutated CFTR gene. While CRISPR-Cas9 technology has proven proficient, safety and efficacy remain a concern. As shown in Schwank’ s and Koo’ s study, an offtarget( or even an accidental on-target) mutation remains a problem. CRISPR-Cas9 technology still is not completely perfect in its desired function, and could possibly produce disastrous results for a patient’ s safety and health. If countless unintentional mutations occur de to CRISPR-Cas9, the efficacy would be extremely questionable.
Despite these concerns, CRISPR-Cas9 technology still remains as a primary candidate for potentially curing Cystic Fibrosis. With seventy thousand people suffering from the genetic disease, CRISPR-Cas9 stands as a hopeful procedure for each one. If Cystic Fibrosis is eventually cured due to this genetic technology, the benefits would be tremendous; for example, other genetic disease studies would soon incorporate similar methods of mutation correction. Studying CRISPR- Cas9’ s effects on Cystic Fibrosis is only the first step in a long-fought battle towards correcting mutated genes from countless genetic malignancies. With victory in sight, the battle of curing the incurable inches closer to an end.
Colemeadow, Josie, Holly Joyce, and Victor Turcanu. " Precise Treatment of Cystic Fibrosis –
Current Treatments and Perspectives for Using CRISPR." Taylor and Francis
Online. Taylor and France, 16 Feb. 2016. Web. 30 Nov. 2016. " Cystic Fibrosis Foundation." Cystic Fibrosis Foundation. Cystic Fibrosis
Foundation, n. d. Web. 30 Nov. 2016. " Epithelial Tissue." Anatomy & Physiology. Anatomy & Physiology, 1 June
2013. Web. 30 Nov.
2016. Fanen, Pascale, Adeline Wohlhuter-Haddad, and Alexandre Hinzpeter.
" Genetics of Cystic
Fibrosis: CFTR Mutation Classifications toward Genotype-based CF Therapies." ScienceDirect. Elsevier, 12 Mar. 2014. Web. 30 Nov. 2016. " Genetics and Nutrition." Genetics and Nutrition. Genetics and Nutrition, n. d.
Web. 30 Nov.
2016. Schwank, Gerald, and Bon-Kyoung Koo. " Functional Repair of CFTR by CRIS-
PR / Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients." Cell Stem Cell.
Medical Research Council Stem Cell Institute, 5 Dec. 2013. Web. 30 Nov. 2016.
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