Creation of De Novo Cryptic Splicing for ALS and FTD Precision Medicine

Loss of function of TDP - 43 is a hallmark of ALS. Wilkins et al. describe a reporter system that uses the activation of cryptic exon splicing caused by TDP - 43 loss - of - function to selectively express therapeutic constructs in diseased cells. They develop a computer - based directed evolution algorithm to assist in reporter design, showing potential beneficial effects in vitro and in vivo.