CRISPRoff - the new frontier for reversible epigenetic editing

Описание: CRISPR-Cas9 is a system that induces double stranded breaks (DSBs) at programmed sites of interest that can be used to generate insertions/deletions (indels) to disrupt gene expression or for precise genome editing. However, DSBs are toxic for a cell and these gene editing approaches depends upon the cells ability to repair the damage...so to some extent the repair is unpredictable. Whilst newer approaches for precise genome editing such as base editing and prime editing have circumvented DSBs, the alternative way of disrupting genes through indels is by using CRISPRi/CRISPRa or epigenetic editing. Since the latter don't change the DNA sequence it is hard to determine if the editing will be heritable and past onto daughter cells and if the gene expression silencing/activation persists without the CRISPR complex. However, it has the desirable effect that the changes can be more easily reversed.

In a recent Cell paper these problems are addressed and the new tool CRISPRoff is introduced. This CRISPR complex contains KRAB domains and DNMTs to silence gene expression of a gene of interest. It is shown in the study to be more effective than current approaches, heritable for up to 15 months, work through differentiation and work at the majority of human genes. And also, they show that gene expression can be restored using CRISPRoff's antagonist CRISPRon.

These new tools will be a great addition for scientists to further research the role of epigenetics in gene expression and to understand different genes but also has potential value for future therapeutics. And so CRISPRoff seems the new frontier for reversible epigenetic editing.

TIMESTAMPS;
Intro - 00:00
CRISPR problems - 01:20
Epigenetic editing - 04:00
New problems and CRISPRoff - 06:00
CRISPRon (reversing editing) - 11:00
Stem cells & neurons - 12:00

REFERENCES:
Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing https://doi.org/10.1016/j.cell.2021.0...

Check out ‪@LongevityScienceNews‬ latest video -    • This could shorten your lifespan | Lifespa...  

Icons in intro; "https://www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com