Using DNA to delete disease

DNA is obscured by closed chromatin, an innately protective structure made up of proteins that interact with each other and with DNA. New activation associated proteins (AAPs) can be custom-built to bind near and open up chromatin so that DNA is made more accessible to gene-editing molecules like CRISPR. CREDIT: illustration by Karmella Haynes

Article Highlights

Protein editorial assistants are clearing the way for cut-and-paste DNA editors, like CRISPR, to access previously inaccessible genes of interest. Opening up these areas of the genetic code is critical to improving CRISPR efficiency and moving toward futuristic, genetic-based assaults on disease.
“The innovation in this paper is having another protein co-delivered with the CRISPR DNA editor, moving chromatin packaging out of the way, so CRISPR has greater access to the DNA,” said lead author Karmella Haynes, from Arizona State University and Emory University.
Haynes describes chromatin blocking as “the elephant in the room” in CRISPR discussions, but it wasn’t directly proved until 2016, when Haynes’ team conducted some clever experiments capturing the effect. Her team is trying to fix the problem by investigating different methods of chromatin disruption.
“The idea is that if CRISPR needs to bind in the middle of a gene but can’t bind close enough to edit the mutation, you could send in our chromatin-opening protein to right outside that hard-to-bind region, rearrange the chromatin, and make the DNA across that gene more accessible for CRISPR to edit the gene,” explained Haynes, who is keen for others to use her system to improve CRISPR efficiency. She pointed out the AAPs can be adapted to target different genes, simply by switching the DNA-binding regions.

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