Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-16806-4
Keywords
-
Categories
Funding
- Jackson Laboratory
- National Human Genome Research Institute [1R01HG009900]
- National Cancer Institute [P30CA034196]
- Leukemia Research Foundation New Investigator Grant
- Jackson Laboratory Director's Innovation fund [19000-17-31]
- Jackson Laboratory Cancer Center New Investigator Award
- National Cancer Institute of the National Institutes of Health [P30CA034196]
Ask authors/readers for more resources
Alternative splicing allows expression of mRNA isoforms from a single gene, expanding the diversity of the proteome. Its prevalence in normal biological and disease processes warrant precise tools for modulation. Here we report the engineering of CRISPR Artificial Splicing Factors (CASFx) based on RNA-targeting CRISPR-Cas systems. We show that simultaneous exon inclusion and exclusion can be induced at distinct targets by differential positioning of CASFx. We also create inducible CASFx (iCASFx) using the FKBP-FRB chemical-inducible dimerization domain, allowing small molecule control of alternative splicing. Finally, we demonstrate the activation of SMN2 exon 7 splicing in spinal muscular atrophy (SMA) patient fibroblasts, suggesting a potential application of the CASFx system. Control over splicing could be used for both therapeutic and engineering applications. Here the authors create artificial splicing factors using RNA-targeting CRISPR systems under small molecule control.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available