CRISPR has ushered in an era of genomic medicine. A number of powerful tools have been developed from the popular CRISPR-Cas9 to cure genetic diseases. But there is one last mile problem – these tools must be delivered efficiently to every cell in the patient, and most Cas9s are too large to fit into popular genomic therapy vectors, such as adenovirus-associated virus (AAV). [1]

Figure 1. Discovery offers starting point for better gene-editing tools

Figure 1 shows the researchers used cryo-electron microscopy (Cryo-EM) to visualize the IscB-ωRNA molecule from a transposon system in high resolution. They were able to capture snapshots of the system in different conformational states. They were even able to engineer slimmer IscB variants, by removing nonessential parts from IscB. [2]

CRISPR-Cas9 systems use an RNA as a guide to recognize a sequence of DNA. When a match is found, the Cas9 protein snips the target DNA at just the right place; it's then possible to do surgery at the DNA level to fix genetic diseases. The cryo-EM data gathered by the Cornell team show that the IscB-ωRNA system works in a similar way, with its smaller size achieved by replacing parts of the Cas9 protein with a structured RNA (ωRNA) which is fused to the guide RNA.

As small as IscB is compared to CRISPR Cas9, the researchers believe they will be able to shrink it even smaller. They've already removed 55 amino acids without affecting IscB's activity; they hope to make future versions of this genome editor even smaller and hence even more useful. [3]

The research was funded by grants Ke received from the National Institutes of Health. Schuler is supported by the Department of Defense through the National Defense Science and Engineering Graduate Fellowship Program. The Cryo-EM work was assisted by the Cornell Center for Materials Research and the Brookhaven National Laboratory. [4]

References:

1. https://www.tamilbloggers.xyz/discovery-offers-starting-point-for-better-gene-editing-tools/
2. https://phys.org/news/2022-05-discovery-gene-editing-tools.html
3. https://www.sciencedaily.com/releases/2022/05/220526151806.htm
4. https://www.labmanager.com/news/discovery-offers-starting-point-for-better-gene-editing-tools-28176

Cite this article:

Thanusri swetha J (2022), Discovery offers starting point for better gene-editing tools, Anatechmaz, pp.156