A quick squeeze helps CRISPR turn skin cells into neurons more efficiently
Human cells hold about two meters (6.6 feet) of DNA, folded and compacted to fit inside a nucleus. That packing is essential for life, but it creates a problem for scientists. Some of the genes that control a cell's identity are buried so deep in tightly packed DNA that gene-targeting tools such as CRISPR activation, or CRISPRa, struggle to reach them.
UCLA researchers have discovered a promising technique to improve the efficiency of converting skin cells into neurons using CRISPR activation, or CRISPRa. The study, published in Matter, describes a method that temporarily loosens tightly packed DNA within the nucleus, allowing CRISPRa to access and activate genes that are otherwise difficult to reach.
This approach significantly boosts the success rate from around 3% with CRISPRa alone to about 40% in mouse cells. The technique, called mechanically enhanced CRISPR-mediated activation (MECA), involves briefly squeezing the nucleus for just milliseconds, which opens up regions of the genome that are normally inaccessible. By identifying the specific genome regions that become more accessible after squeezing, researchers can design and guide CRISPRa to more effective sites for activating genes that control cell identity.
This method could potentially be used to convert patient skin cells into various cell types, such as neurons, heart cells, or even replacement tissue, reducing the likelihood of rejection by the patient's immune system. The researchers are now planning to test the technique for other types of human cell conversions and explore its potential applications in drug testing and transplantation.
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