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Regulated control of gene therapies by drug-induced splicing. | LitMetric

AI Article Synopsis

Article Abstract

So far, gene therapies have relied on complex constructs that cannot be finely controlled. Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The small-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain. Moreover, the switch system, which we denote X, does not require the co-expression of any regulatory proteins. Using X, the translation of the desired elements for controlled gene replacement or gene editing machinery occurs after a single oral dose of the inducer, and the robustness of expression can be controlled by the drug dose, protein stability and redosing. The ability of X to provide temporal control of protein expression can be adapted for cell-biology applications and animal studies. Additionally, owing to the oral bioavailability and safety of the drugs used, the X switch system provides an unprecedented opportunity to refine and tailor the application of gene therapies in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966400PMC
http://dx.doi.org/10.1038/s41586-021-03770-2DOI Listing

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