Mitochondrial Gene Editor
For this assignment, I chose Lee Jack’s article titled, “A bacterial toxin enables the first mitochondrial gene editor,” published on ScienceNews in July 2020. With the advancement in gene therapy, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated with Cas 9 proteins, the gene-editing tool is the preferred and most frequently used tool. The tool works through various mechanisms; CRISPR recognizes and integrates the genomic code of invading microorganisms, while the Cas 9 proteins target the invading microorganisms. Therefore, the CRISPR Cas 9 works by attacking invaders in a sequence-specific manner in the nuclei by cleaving the invaders. However, this tool is limited to the nucleus, which led scientists to the discovery of the Mitochondrial Gene Editor from bacterial toxins. The discovery was made by a microbiologist at the University of Washington in Seattle, Marcos de Moraes. A mitochondrial gene-editing tool was therefore developed to edit mitochondrial DNA.
According to Lee, the CRISPR Cas 9 genetic editing tool works in a couple of steps that involve the recognition of invaders, integration of invader genomic sequence, and interference through cleaving. Therefore, CRISPR Cas9 is a form of adaptive immunity. Additionally, after the integration of invader genomic sequence, CRISPR Cas 9 recognizes reoccurring viruses and diseases and helps the immune system fight them through the cleaving of their DNA or RNA. CRISPR is transcribed in long precursor crRNA, which cleaves the nuclei’s targeted invaders into single strands, which also cannot edit the mitochondrial DNA. This tool is used in the research toward curing genetic disorders and diseases through the cleaving of DNA, thereby editing the sequence and eradicating the disorder and diseases. Subsequently, the tool has been used in therapeutic processes, antimicrobial tools and treatment systems, and genome editing. This tool’s limitation led to the discovery of a tool that works on invaders in the mitochondria.
The discovery of the tool that targets DNA in the mitochondria was achieved by genetic engineering of a protein emitted as a toxin by the bacteria to kill other microbes. Diseases and disorders caused by mutations in mitochondrial DNA would continue to prevail in the absence of this tool. Moreover, without the targeting of mitochondrial DNA, gene therapy cannot be admitted without genetic editing. This discovery was, therefore, significant in gene therapy. Gene editing occurs when DNA or RNA is cleaved or joined with the replacement of some DNA bases with other bases.
The bacteria Burkholderia cenocepacia secretes the protein toxin that kills other microbes. This protein toxin creates a tool editor that is mitochondria-favorable, and therefore, it is used to target DNA in the mitochondria. The protein toxin kills other microbes by causing mutations in the microbe’s DNA that are destructive. The protein toxin causes this harmful mutation by attaching itself to the microbes’ DNA strands and converting the cytosine to thymine, which leads to the killing of the microbes. The protein toxin, therefore, works as a cytosine convertor protein. Just as it was lethal against the microbes, it behaved the same in the mammalian cell and caused multiple destructions. Subsequently, a chemical biologist, David Liu, joined the research and found a way to remove the toxin’s destructive factor in a mammalian cell.
The destructive factor of the toxin protein led to the destruction of DNA in the mammalian cell. Subsequently, the correction to this setback involved dividing the protein toxin into halves that wouldn’t convert the cytosine into thymine independently but together. This development led to the advancement in the mitochondrial editing tool. Therefore, this meant that the two halves had to be directed in opposite directions to prevent their destructive actions. Consequently, the scientists came up with a method of directing the enzymes. It involved the attachment of TALE proteins, which were to be used in the targeting of specific DNA sequences, which initiated the conversion at the targeted sequences only. The tool also had a high efficiency percentage.
Additional research is to be done on the tool to ensure it is used in gene therapy. Since the protein toxin is the first mitochondrial editing tool, further advancements in research will lead to the discovery of more tools that can edit mitochondrial DNA. Additionally, with forty-nine percent in efficiency, advancement in research will improve the efficiency to close to a hundred percent percent. Finally, another result of further advancement in this research is the application of the tool in gene editing by the successful editing of mitochondrial DNA. Other tools have also been developed for use in gene therapy, such as TALENS and base editors. The TALENS are used as molecular scissors for mitochondrial DNA in mice, while the base editors edit the DNA bases such as cytosine, guanine, adenine, and thymine into another base. These base editor tools do not work on mitochondrial DNA but on nuclei DNA.
In conclusion, the mitochondrial genetic editing tool is a significant advancement in gene therapy. Initially, previous tools could not target mitochondrial DNA, but this protein toxin targets mitochondrial DNA. Additionally, it has an advantage over other genetic editing tools in that it causes changes in double-stranded DNA without splitting the strands into single strands. For tools such as CRISPR Cas9, the DNA strand is split into two single strands, and then the recognition, integration, and cleaving occur. The mitochondrial editing tools are, therefore, more efficient and fast compared to other tools. It also prevents a number of disorders and diseases caused by mitochondrial DNA mutations. The mitochondrial genetic tool is, therefore, a significant advancement in biotechnology and gene therapy.
Work Cited
Lee, Jack. J. “A Bacterial Toxin Enables The First Mitochondrial Gene Editor.” Science News, 2020, https://www.sciencenews.org/article/mitochondria-gene-editing-bacterial-toxin-crispr.
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Question 
Identify an article that has appeared in a print periodical OR reputable science/news website since January 1st of 2018 that is related, at least loosely, in some way to the subject matter of the module (e.g., life, energy, nutrition, genetics, climate change, bioethics, biotechnology, etc.). This should be a news article. DO NOT use a textbook or “encyclopedia”-type source.
Mitochondrial Gene Editor
Briefly summarize the article, describing direct and indirect connections to course topics/discussions.
Briefly describe TWO implications/applications implied, surfaced, and discussed in the arti cle, and their significance.
Include descriptions of TWO important or critical questions raised in/by the article.
It is important that the paper be well written, properly sourced/cited (any standard format), 3-5 pages (12pt, 1”
margins, double-spaced). THREE FULL PAGES of text IS AN ABSOLUTE MINIMUM. This length will NOT INCLUDE headers (e.g., your name), figures, references, etc.