biostudies-literatureWan LNCI NIH HHSNIGMS NIH HHS188-198https://www.ebi.ac.uk/biostudies/studies/S-EPMC11387002biostudies-literatureUnknown34(4)Aberrant alternative splicing is emerging as a cancer hallmark and a potential therapeutic target. It is the result of dysregulated or mutated splicing factors, or genetic alterations in splicing-regulatory <i>cis</i>-elements. Targeting individual altered splicing events associated with cancer-cell dependencies is a potential therapeutic strategy, but several technical limitations need to be addressed. Patient-derived organoids are a promising platform to recapitulate key aspects of disease states, and to facilitate drug development for precision medicine. Here, we report an efficient antisense-oligonucleotide (ASO) lipofection method to systematically evaluate and screen individual splicing events as therapeutic targets in pancreatic ductal adenocarcinoma organoids. This optimized deliveNucleic acid therapeuticsScreening Splice-Switching Antisense Oligonucleotides in Pancreas-Cancer Organoids.PMC11387002F30 CA271804T32 GM008444P30 CA045508P01 CA013106Danielsen MKral AJSchafer BKrainer ARWan LSudheendran KCaruthers MHVoss DfalseScreening Splice-Switching Antisense Oligonucleotides in Pancreas-Cancer Organoids.Aberrant alternative splicing is emerging as a cancer hallmark and a potential therapeutic target. It is the result of dysregulated or mutated splicing factors, or genetic alterations in splicing-regulatory <i>cis</i>-elements. Targeting individual altered splicing events associated with cancer-cell dependencies is a potential therapeutic strategy, but several technical limitations need to be addressed. Patient-derived organoids are a promising platform to recapitulate key aspects of disease states, and to facilitate drug development for precision medicine. Here, we report an efficient antisense-oligonucleotide (ASO) lipofection method to systematically evaluate and screen individual splicing events as therapeutic targets in pancreatic ductal adenocarcinoma organoids. This optimized delive2024-01-01T00:00:00Z2024 Aug2026-04-12T19:18:22.981Z2026-04-07T13:17:41.282ZS-EPMC113870023871683010.1089/nat.2023.0070