‘Chemical surgery' can correct genetic mutations behind many diseases

     The breakthrough of DNA base editing brings hope of potential treatment for lot of diseases that arise as the result of a single genetic ‘misspelling’. Researcher discovered a method/process that can correct a type of genetic mutation behind some diseases. There are plethora of human genetic variations associated with disease, while many diseases involve several variations, a huge amount including sickle cell anemia; that results in genetic misspelling, known as a “point mutation.” There is an error in one of the stages of the DNA double helix structure that are made of bases, Adenine, Thymine, Cytosine, and Guanine A-T, G-C. Around 20,000 known point mutations that are linked to diseases are down to bases that must be G instead of being A, and their corresponding pair being a T instead of C. Well, scientists say that they can fix these errors in a process called base editing, turning A base back to G and T base back to C using a modified version of the gene editing tool CRIPR-Cas9. CRISPR allows scientists to precisely target and edit pieces of the genome, it is a molecule made of RNA, that allows a specific site of interest on the target, DNA double helix. The RNA molecule is attached to a bacterial enzyme that unwinds the DNA and works as a pair of molecular scissors to cut it at the exact point required. This allows scientists to cut, paste and delete single letters of genetic code.     

     David Liu, the co-author from the Broad Institute of MIT and Harvard and some other researchers, were using base editing to try to study or authenticate potential future therapeutic treatments for blood diseases, genetic deafness, genetic blindness and some neurological disorders. Within the new machinery, a section of single-stranded genetic material known as RNA directs the tool to the faulty section of DNA, which the Cas9 protein then unwinds. Certain developed enzyme within the tool then chemically alters the A base, turning it into a molecule known as inosine, which is read as G by the machine. Significantly, the Cas9 protein used in the tool has been shuffled so that it cannot split the two strands of DNA, as is typical with gene-editing techniques. Rather, the editing tool only makes a mark in the opposite strand of DNA near the error base, deceiving the cell into replacing the DNA strand around the site. That mark helped the cell to replace the T with a C, because the base opposite the T has been converted to inosine, which pairs with C, adding the mark had showed approach to work in both the cells of bacteria and of humans.

      This technique has some advantages over traditional Crispr-Cas9 techniques for switching base pairs, not least that it is less prone to problems of random insertions or deletions, was not found to cause unwanted changes to the base pairs, and works well in adult cells. However, Dr. Liu noted that base-editing cannot be used to insert or delete stretches of DNA. Dr. Liu cautions, that more work will be needed to cure diseases, there are many additional steps beyond simply making the mutation that may be needed to treat [a] disease. Well, many genetic diseases are due to mutations where a single base pair has been substituted for another, this makes these new base editing methods of great value in both basic research to make disease models and, in theory to correct genetic disease; making either non-hereditable or hereditable alterations. Since the changes formed using the tool do not occur in the DNA, they only temporarily alter the proteins generated – a development that could not only avoid some of the ethical dilemmas around gene editing, but also offer ways to tackle diseases caused by temporary changes within a cell, such as inflammation. 

     Dr. Lieu said “I am hopeful that as complementary approaches, DNA base editing and RNA base editing will together enable an especially broad set of potential research and therapeutic applications” (Davis). 

Reference:

Davis, N. (2017, November 1). 'Chemical surgery' could treat diseases by fixing genetic mutations. Retrieved November 3, 2017, from https://geneticliteracyproject.org/2017/11/01/chemical-surgery-treat-diseases-fixing-genetic-mutations/

Davis, N. (2017, October 25). 'Chemical surgery' can correct genetic mutations behind many diseases – study. Retrieved November 03, 2017, from https://www.theguardian.com/science/2017/oct/25/chemical-surgery-can-correct-genetic-mutations-behind-many-diseases-study