SpliceRUSH: CRISPR-dCas13d-based deep screening of proximal and distal splicing-regulatory elements

Pre-mRNA splicing is an important step in gene expression. Antisense oligonucleotides (ASOs) can therapeutically modulate splicing by competing against endogenous splicing factors. The ASO therapeutic Spinraza/nusinersen, is the first efficacious treatment for spinal muscular atrophy (SMA), targeting an intronic splicing silencer downstream of Survival Motor Neuron 2 (SMN2) exon 7, rescuing SMN protein production in SMA patients.
The process for discovering ASO targets is time intensive and expensive. In this publication highlight, Chaolin Zhang, Ph.D., and Yow-Tyng Yeh, Ph.D., of Columbia University discuss SpliceRUSH, a high-throughput screening method that uses a CRISPR-dCas13d RNA-target system that exploits the similar mode of action of ASOs to uncover proximal and distal splicing-regulatory elements (SREs). When applied to SMN2, SpliceRUSH identifies not only the known therapeutic targets, but also uncovers a previously unknown distal intronic SRE.
#crispr #scienceandtechnology #geneexpression
Read the full paper here www.ncbi.nlm.n...
Visit the Chaolin Zhang Lab zhanglab.c2b2....
Code Availability
The scripts used for this study are available at github.com/cha...
GenomeTDCC www.genometdcc...
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