Imagine being able to have your genes edited to eradicate errors and to greatly lengthen quality of life and life span. There are some people that are still active and independent at the age of 100 and live well beyond that. Generally those people also had long lived parents. What if the same genetic traits they inherited and more could be given to anyone?
Researchers at the Joint Institute of Metrology and Biology (JIMB) have recently developed MAGESTIC, a new CRISPR platform that is similar to a word processor which makes gene editing using barcodes. CRISPR which snips at DNA has been a clumsy tool making precision medicine or ?clipping? disease causing genetic mutations in patients virtually impossible. MAGESTIC or ?multiplexed accurate genome editing with short, trackable, integrated cellular barcodes? is being compared to a word processer that enables efficient search and replace functions for genetic material. This new platform was also able to produce an increase of sevenfold in survival of cells during the process of editing.
Previously, CRISPR required a very extensive understanding of how repair cuts with cells at a variety of sites across the genome could be controlled as needed. Because DNA strands are able to rejoin in very unpredictable ways, random mutations are likely to occur at the cut sites in the DNA of the cells. Additionally, many cells will not survive the process of editing at all. It has been extremely challenging building very accurate predictions of gene editing. Researchers want a more reliable way for programming CRISPR to be able to cut at targeted locations in the genome and then be able to direct cells for designed edits at the cut sites of the DNA. This can be accomplished by providing a donor DNA for the cell which the cell?s DNA repair machinery is able to use as a template for replacing the original sequence at the original cut site. However, the cell?s DNA repair system is complex and will not always behave predictably.
The cell searching for a DNA donor suitable for repairing a cut site is a huge challenge for the cell. The repair machinery of the DNA has to search through millions and even billions of DNA base pair sequences to be able to find the correct donor DNA. MAGESTIC has provided a significant advance in gene-editing technology by helping the cell search by artificially recruiting the DNA designed donor through a process called active donor recruitment which will recruit the donor DNA right to the cut site. This recruitment resulted in a sevenfold increase in the cell?s survival which was a change that resulted in increased effectiveness and efficiency.
The other feature that was different from CRISPR, was MAGESTIC?S new version of cellular barcode. Previously, researchers used small bits of circular DNA also known as plasmids to guide DNAs and to store barcodes for tracking designed mutations to each cell. The plasmids will multiply with cell growth and are inherited by both cells following cell division. With MAGESTIC the barcodes are integrated into chromosomes as opposed to single barcode per item correspondence which can vary widely in number resulting in 10 to 40 appearing in every cell.
Scientists do not know much about the function of the 0.l% of code that will vary between individuals in any population and is responsible for differences in susceptibility of disease. MAGESTIC helps to address the gap in understanding natural genetic variation through enabling individual genetic variant to be edited very precisely and compared to other genetic variants one by one. This results in help in uncovering which genetic differences will have cellular impact function. MAGESTIC will also edit all at one time in just a single test tube with every edit happening in any one of a million otherwise cells that are identical.
The researchers have reached a state where they have achieved sequencing the order of genome base pairs and are also able to change them. Additional research is needed to understand the edit sequencing.
To view the original scientific study click here: Multiplexed precision genome editing with trackable genomic barcodes in yeast