Successfully Deleting Disease by Opening up DNA
Bioengineers based in the US have designed a “DNA-binding editorial assistant” that will allow gene-editing technology, like CRISPR, to access previously inaccessible genes of interest. Published in APL Bioengineering, the new protein design can be used to open up areas of the DNA that are obscured by chromatin, which would improve CRISPR efficiency and aid in developing more precise gene-editing techniques to combat some genetic diseases.
DNA is wrapped up in a packaging called chromatin that can activate or silence genes at any moment. This chromatin packaging has made it difficult for scientists to develop accurate gene-editing techniques to edit disease-causing mutations, and has been proven in previous studies that showed that silenced chromatin reduces CRISPR/Cas9 editing. CRISPR gene-editing has been successful for some specific applications, but since chromatin is very complex and varies between mammalian cell types, it can still pose a barrier to reliable and consistent use.
In the new technique developed by the US-based team, another protein is co-delivered with the CRISPR DNA-editor which moves chromatin out of the way. This allows CRISPR to access more of the DNA to reach its target gene.
They targeted a gene encoding an easily detected luminous protein called luciferase which can be turned on or off by the chromatin packaging. In the chromatin-packed state, several editorial assistants, called DNA-binding transiently expressed activation-associated proteins (AAPs), were found to disrupt the chromatin and allow CRISPR to edit the luciferase gene successfully and accurately.
This new development will be extremely useful for times when CRISPR is needed to edit in the middle of a gene that may hidden behind chromatin. The chromatin-opening protein can rearrange DNA to make it more accessible. AAPs can also be adapted to target different genes, and other genes nearby the target site will not be disrupted.