Scientific Literature Essay
The purpose of this essay is to analyse the contents of a secondary (‘The Role of Gene Editing in Neurodegenerative Diseases’) and primary article (‘Modeling familial Alzheimer’s disease with induced pluripotent stem cells’) and then compare the two. The journal the review article is associated to must also be examined for a more thorough understanding of the field. The disciplines involved with both articles and the journal must also be researched and included.
Review Article – ‘The Role of Gene Editing in Neurodegenerative Diseases’:
The chosen review article comes from the journal ‘Cell Transplantation’ and involves the scientific disciplines of human biology, neurology, genetics and pathology.
Human biology is a broader discipline and has a focus on the biology of humans from the internal structures (e.g. cells, tissues) as well as interactions we have with the environment. This is relative to the article in analyzing the environments effect on the diseases and also how these diseases function and interact inside the body on a cellular level. Neurology is a study of the nervous system, of which these diseases are impacting e.g. Alzheimer’s disease effect on brain function. Genetics involves the study of genes and traits such as the development of disease which assists in understanding the extent to which neurodegenerative diseases are hereditary. Pathology is the study of diseases e.g. neurodegenerative disease which are explored in this article.
The article does not specify its intended audience but it can be inferred the target audience is researchers or individuals involved in the aforementioned disciplines and studying the diseases or perhaps family members of/or patients looking into possible treatments.
This article focuses on and analyses how gene editing tools such as CRISPR/CAS (clustered regularly interspaced short palindromic repeats–associated nucleases) and ZFNs (zinc-finger nucleases) can be applied to and affect neurodegenerative disorders, specifically analysed in the article are Alzheimer’s, Huntington’s, and Parkinson’s disease.
Neurodegenerative disorders are “medical conditions with progressive failure of neuronal networks and eventually the death of neurons” and do not have “precise diagnostic tools or definite treatments”, therefore sufferers will not be able to fully recover or recover at all from these diseases. The causes for neurodegenerative diseases have not been proven but “evidence suggests that genetic, cellular, and circuit alternations may cause the generation of abnormal misfolded proteins” which then leads to the damage caused by neurodegenerative diseases and is recurring across the diseases researched. Gene editing tools have allowed testing for drugs on neurodegenerative diseases and editing the genes of patients to try and allow them to regain function and improve daily life.
Journal – ‘Cell Translation’:
The review article originates from “Cell Transplantation (CLL), the Regenerative Medicine Journal is an open access, peer reviewed journal” and is multi-disciplinary journal aiming at a variety of audiences in the fields of science and medicine. The journal is a member of Committee on Publication Ethics (COPE). It explores cell transplantation and how it can be applied to diseases affecting humans, it also covers advancements in technology, research and studies involving this field of work.
Primary Article – ‘Modeling familial Alzheimer’s disease with induced pluripotent stem cells’:
Although the aim and hypothesis are not directly stated it can be inferred that the aim is to ‘model Alzheimer’s disease with iPSCs’ and the hypothesis is that the ‘iPSCs will model Alzheimer’s. The idea of iPSCs is used throughout the review article in explaining the uses and results of gene editing tools. The results show FAD-iPSC neurons were successful in modeling Alzheimer’s. This is significant as it will allow researchers to use a proven cause of studying neurodegenerative diseases.
The review article was quite scientific and occasionally hard to understand but with some prior knowledge from biology, genetics and research the article makes sense. ZFNs were reasonably easy to understand how they affected disease while TALENS and CRISPR/CAS were much harder and required a lot of further research due to abbreviations of proteins and genes etc.
ZFNs:
ZFNs have proven to be successful in countering neurodegenerative diseases. Parkinson’s disease includes a missense (point mutation resulting in a different amino acid being coded) of the SNCA gene, this can be genetically repaired by ZFNs without affecting the rest of the genome. This results in less damage caused by the mutation therefore showing a positive effect of iPSC (induced pluripotent stem cell) treatment in reversing abnormal phenotypes such as those caused by Parkinson’s disease.
In Huntington’s disease ZFNs were beneficial in animal models involving mice. In vivo the ZFNs “repressed the mutant HTT in the brain and improved their functions” and a drug designed to target the mutant DNA sequence was successful in another mouse model in repressing the HTT gene as well as its symptoms being improved.
Overall the evidence shows ZFNs could be a viable option in treating genetic disorders.
TALENs:
TALENs have had mixed results as a gene editing tool. It was successful in correcting the HTT exon 1 in human iPSCs (HD-iPSCs) and reduced many symptoms of Huntington’s disease e.g. HD-iPSCs are associated with cell death which was reversed by TALENs.
The downsides to TALENs however are the size of the DNA/mRNA affects its efficiency as a gene editing tool as well as the skill and knowledge needed to successfully design the required the gene editing tool causes researchers to prefer a simpler option.
CRISPR/CAS:
CRISPR has proved to be successful and precise at modifying genes. In Huntington’s disease specifically, the CRIPSR/CAS9 system was utilized to halt the expression of the HTT gene in human cells. Due to the success a pig model was presented to further research how it could be affected against other neurodegenerative disease.
There are negatives to this gene editing tool such as CRISPR requiring a PAM (protospacer adjacent motif) adjacent to target area, “variable efficiencies of delivery methods” and the chance of cell death and transformation due to a high rate off-target effects compared to the other options.
The review article is analyzing specific gene editing tools against certain neurodegenerative diseases while the primary journal article focuses solely on Alzheimer’s disease but is still relevant to the disciplines covered in the review. The journal article is specifically about modeling Alzheimer’s with iPSCs to be able to identify it and study the disease. This idea of iPSCs is consistently brought up in relation to all neurodegenerative diseases in the review in identifying and modeling them especially through animals which allows researchers to accurately study them and look for treatments.
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