Image Source: Thimas Splettstoesser & Wikipedia, CC BY SA 4.0

In recent studies, scientists were able to capture some high-resolution, 3D images of an enzyme which was on the verge of cutting the exact DNA strands. According to scientists, the findings will help them in cracking the way of altering the specific genes. This will also help in the future treatment of a lot of human diseases which are caused by the DNA mutations which also includes cancer, cystic fibrosis, and Huntington disease. The images were captured by using a technique known as cryogenic electron microscopy, or cryo-EM. The images gave scientist a chance to understand the gene-editing tool known as CRISPR-Cas9 works more precisely. The doctors will also be able to alter the specific genes by using this gene editing tool. UBC researcher Sriram Subramaniam, leader of the Cyro-EM studies said, “It is exciting to be able to see at such a high level of detail how Cas9 actually works to cut and edit DNA strands. Subramaniam is awarded the Canada Excellence Research Chair in Precision Cancer Drug Design. Subramaniam runs a laboratory which works on finding new solutions and discoveries in cancer neuroscience and infectious disease. The first author of the study is Xing Zhu and the members of the study include the co-author Sagar Chittori are members of the Subramaniam laboratory at UBC.

Image Source Janet Iwasa/ Univ. Utah

These images provide us with invaluable information to improve the efficiency of the gene-editing process so that we can hopefully correct disease-causing DNA mutations more quickly and precisely in the future.” Talking about the CRISPR-Cas9, it is a gene-editing tool which used to cut the DNA strands as the enzym known as Cas9 works as a pair of molecule scissors. When the cuts are made by using the enzyme Cas9, it enables the doctors to work on the insertions and other changes that they desire to make during the change of the DNA sequence. This extraordinary solution allows doctors to work on dangerous diseases like cancer and life taking cystic fibrosis. If this process works, it is going to be groundbreaking research in the history of genetics and DNA. The research was published in the journal Nature Structural and Molecular Biology. The reason behind using the imagery system cryo-EM tech was to understand the sequence of the things that have to be done during the process. When Subramaniam and his team used the Cryro-EM technology to capture the three-dimensional images of CRISPR-Cas9, the images enabled the scientists to look at the molecular motions that take place in the process of the DNA strand cutting by Cas9. They also captured the image of the cut DNA which was still attached to the enzyme before its detachment.

“One of the main hurdles preventing the development of better gene-editing tools using Cas9 is that we didn’t have any images of it actually cutting DNA,” said the study’s co-senior author, University of Illinois researcher Miljan Simonovic. “But now we have a much clearer picture, and we even see how the major domains of the enzyme move during the reaction and this may be an important target for modification.” Subramaniam and his team became the first ones to capture the atomic resolution images of protein-bound drug molecules and proteins by using Cyro -EM. The Subramaniam laboratory has been working on this project for a long time now and it also gave them an opportunity to expertise the use of Cyro-Em by which they identified different proteins which includes metabolic enzymes, brain receptors, and DNA-protein complexes. The research was funded by the US National Cancer Insititute, National Institutes of Health Gants, the UIC Center of Clinical and Translation Sciences, and by a Canada Excellence Research Chair position awarded to Subramaniam.


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