ArticleNature biotechnology2022
Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells.
Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 59 citations in OpenAlex.
- Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Divergent RNA structures support accurate splicing of the SF3B1-sensitivebioRxiv : the preprint server for biology · 2026Article
- Outstanding Questions to Understand and Target Splicing Factor-Mutant Blood Cancers.Blood cancer discovery · 2026Article
- Co-Opting MBNL-Dependent Alternative Splicing Cassette Exons to Control Gene Therapy in Myotonic Dystrophy.Annals of neurology · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- mRNA processing in cancer immunotherapy: emerging targets, resistance mechanisms, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Generative Design of Cell Type-Specific RNA Splicing Elements for Programmable Gene Regulation.bioRxiv : the preprint server for biology · 2025Article
- KATMAP infers splicing factor activity and regulatory targets from knockdown data.Nature biotechnology · 2025Article
- A portable poison exon for small-molecule control of mammalian gene expression.Nature methods · 2025Article
- Emerging Strategies of Cell and Gene Therapy Targeting Tumor Immune Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Global trends and emerging insights in BRAF and MEK inhibitor resistance in melanoma: a bibliometric analysis.Frontiers in molecular biosciences · 2025Article
- Analysis of SLC genes alternative splicing identifies the SLC7A6 RI isoform as a therapeutic target for colorectal cancer.Cancer science · 2025Article
- Steering research on mRNA splicing in cancer towards clinical translation.Nature reviews. Cancer · 2024Review
- Splicing the Difference: Harnessing the Complexity of the Transcriptome in Hematopoiesis.Experimental hematology · 2024Review
- Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024Review
- Decoding biology with massively parallel reporter assays and machine learning.Genes & development · 2024Review
- Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes.Science (New York, N.Y.) · 2024Article
- Creation of de novo cryptic splicing for ALS and FTD precision medicine.Science (New York, N.Y.) · 2024Article
- Molecular impact of mutations in RNA splicing factors in cancer.Molecular cell · 2024Review
- The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
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20 authors at 4 institutions in 2 countries.
Funding
Abstract
Many cancers carry recurrent, change-of-function mutations affecting RNA splicing factors. Here, we describe a method to harness this abnormal splicing activity to drive splicing factor mutation-dependent gene expression to selectively eliminate tumor cells. We engineered synthetic introns that were efficiently spliced in cancer cells bearing SF3B1 mutations, but unspliced in otherwise isogenic wild-type cells, to yield mutation-dependent protein production. A massively parallel screen of 8,878 introns delineated ideal intronic size and mapped elements underlying mutation-dependent splicing. Synthetic introns enabled mutation-dependent expression of herpes simplex virus-thymidine kinase (HSV-TK) and subsequent ganciclovir (GCV)-mediated killing of SF3B1-mutant leukemia, breast cancer, uveal melanoma and pancreatic cancer cells in vitro, while leaving wild-type cells unaffected. Delivery of synthetic intron-containing HSV-TK constructs to leukemia, breast cancer and uveal melanoma cells and GCV treatment in vivo significantly suppressed the growth of these otherwise lethal xenografts and improved mouse host survival. Synthetic introns provide a means to exploit tumor-specific changes in RNA splicing for cancer gene therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.