Researchers at UC Santa Barbara have developed a new method for genome editing using the Nobel Prize-winning CRISPR/Cas9 technology that increases its efficiency without the use of viral templates. In a paper published in the journal Nature Biotechnology, the team at the lab of biologist Chris Richardson explained that their innovation stimulates homology-directed repair by around threefold without raising the incidence of mutations or affecting end-joining repair outcomes. The CRISPR/Cas9 method deploys a defence method that bacteria utilise to repel viruses, by snipping out part of the virus’s genetic material and exploiting it in order to recognize it later. In genome editing, the technique uses the enzyme Cas9 as cutting tools to remove sequences it recognizes, guided by the CRISPR system. The researchers’ method introduces inter strand cross links into the editing procedure, significantly increasing the chance of success without raising the number of errors and improving scalability and cost-effectiveness.
The methodology is likely to be most useful in ex-vivo gene editing applications, mainly in disease research and preclinical work. The new methodology provides additional resources that will aid the building of disease models and the testing of hypotheses for therapeutic approaches, leading to more efficient, accurate, and cost-effective genome editing technology. The consistent improvement in gene-editing for therapeutic use will significantly benefit the medical field’s progress, allowing researchers for the first time to create much more specialized cell types to develop vaccines and new therapies to combat diseases and medical conditions.
The discovery of this novel method is not only efficient but also minimally error-prone non-viral systems of gene editing that engages targeted DNA repair, makes gene-editing more efficient and expedient, simplifying procedures with the entire process and offering a tool that is suitable for several applications.
Hannah Ghasemi, a lead author of the study, and a member of the Richardson Research Group had been in the process of purifying proteins to study DNA repair when she discovered through an unintended error that cross-linking of homologous repair template DNA enhances gene editing in human cells. She expected negative feedback, but instead, she found a positive impact, the editing activity of the controls increased by up to three times the edited activities without cross-linking. Although the team anticipates an increase in edits, leading to a chance for errors, they discovered no increase in the frequency of mutations covered by the study, and the causes of such outcomes are being investigated.
Richardson further explained “what we think happens is that the cell detects and tries to repair the damaged DNA that we have added this cross-link to and in doing so delays the cell past a checkpoint where it would normally stop this recombination process. And so by prolonging the amount of time that it takes the cell to traverse this recombination, it makes it more likely that the edits will go to completion.” Adopting this style of DNA editing delivers its benefits without the need for viral carriers, which can be toxic, expensive and difficult to scale. The scarcity of viral carriers is another reason why gene editing continues to confront developmental roadblocks. This process offers a more financially viable and scalable option for gene editing, which would enable medical research to improve significantly.
The Coronavirus disease pandemic remains a prime focus of scientific research, making this process a critical and promising development in the world of gene editing, which could help nation-states combat a possible pandemic in the future. The breakthrough in gene editing facilitated through this innovation will contribute to the field of scientific research and continue to contribute to the discovery of treatments for various diseases, which could lead to important and promising advancements in scientific fields with limited healthcare resources.
