Do you need a super active #CRISPR Cas for in vivo editing? I have not one, but two options for you. Activities rival SpyCas9, but they fit into an scAAV. Check out our latest paper, co-led by Fedor Gorbenko and Irene Sala. Just out in Genome Research. link.springer.com/article/10…

We saw the same SP100-dependent toxicity in cells from VODI patients who lack SP110. Regulated condensate disassembly may be a general requirement for maintaining cellular health!

This phenomenon is relevant to any situation where the balance of SP110 versus SP100 expression is perturbed. Not just via interferon upregulation. SUMOylation is also a key regulator of toxicity.

Using cryo-EM and AlphaFold, we found that SP110 physically binds SP100 via their CARD domains. In healthy cells, this interaction sequesters SP100 and dissolves PML bodies in mitosis. Without SP110, SP100 oligomerizes and wreaks havoc on the genome.

What happens when SP110 is missing? SP100 becomes a "toxin." When upregulated, it forms large oligomers that fail to disassemble and persist into mitosis. These persistent SP100-PML bodies coat segregating chromosomes, causing massive DNA damage and genomic instability.

The story started with a genome-wide CRISPRi screen for regulators of the innate immune response. We found that SP110 is a potent inhibitor of interferon-driven cell death. It specifically counteracts the toxic activity of another speckled protein, SP100.

Proper organelle regulation during mitosis is a must, but how do membrane-less condensates like PML bodies behave during cell division? In work led by @eric_aird, we found the balance of speckled proteins SP110 & SP100 to be the key. doi.org/10.1038/s41556-026-0…

ERCC6L2 acts as a guardian during repair of staggered DSBs. This sheds light on ERCC6L2 mutations linked with BMF and leukemia and highlights caution for genome-editing approaches that generate DNA overhangs.

What does ERCC6L2 actually do? It counteracts the activity of the MRN complex (MRE11–RAD50–NBS1), limiting excessive DNA end resection and promoting accurate end joining.

Many genome-editing tools work by cutting DNA - but the shape of the cut matters. Using #CRISPR screening, we show ERCC6L2 is specifically required to maintain #DNArepair fidelity at staggered DNA breaks, but not at blunt ends. nature.com/articles/s41467-0…