Creation of de novo cryptic splicing for ALS/FTD precision medicine.

Wilkins OG, Chien MZYJ, Wlaschin JJ, Pisliakova M, Thompson D, Digby H, Simkin RL, Diaz JA, Mehta PR, Keuss MJ, Zanovello M, Brown AL, Harley P, Darbey A, Karda R, Fisher EMC, Cunningham TJ, Le Pichon CE, Ule J, Fratta P
bioRxiv. 2023 Nov 15:2023.11.15.565967. doi: 10.1101/2023.11.15.565967. Preprint. PubMed Article

Plasmids from Article

ID	Plasmid	Purpose
216152	TDP-REGv2(mScarlet-FLAG)#7 in pTwist-CMV backbone	Expresses mScarlet in cells with TDP-43 loss-of-function. This plasmid has one of the best dynamic ranges of those tested (~100-fold) in SK-N-BE2 cells. It uses a cryptic exon. [Code 'A11']
216153	TDP-REGv2(mScarlet-FLAG)#9 in pTwist-CMV backbone	Expresses mScarlet in cells with TDP-43 loss-of-function. Has one of the best dynamic ranges of those tested (~100-fold) in SK-N-BE2 cells (brighter than #7). It uses a single intron. [Code 'B11'].
216154	TDP-REGv2(mScarlet-FLAG)#10 in pTwist-CMV backbone	Expresses mScarlet in cells with TDP-43 loss-of-function. Leaky but very sensitive to mild TDP-43 loss of function. It uses a cryptic exon. [Code 'B5']
216155	TDP-REGv2(mScarlet-FLAG)#11 in pTwist-CMV backbone	Expresses mScarlet in cells with TDP-43 loss-of-function. Very bright and decent dynamic range (>10-fold), slightly leaky. It uses a single intron. [Code 'B12'].
216156	TDP-REGv2(mScarlet-FLAG) matched positive control in pTwist-CMV	Expresses mScarlet regardless of TDP-43 knockdown.
216162	TDP-REGv2 Triple Cryptic Cre recombinase in pTwist-CMV	Expresses Cre recombinase in cells lacking TDP-43 function
216163	TDP-REGv2 Cryptic PE-Max	Expression of prime editing vector PEMax (Plasmid #174820) but only in cells with TDP-43 loss of function
216164	TDP-REGv2(Gaussia Luciferase)#5 in pTwist-CMV	Expression of secreted Gaussia Luciferase specifically in cells with TDP-43 loss of function
216165	TDP-REGv1(mCherry-FLAG) in pTwist-CMV	Expression of mCherry specifically in cells with TDP-43 knockdown. Uses AARS1-derived cryptic exon to control mCherry expression.