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| Status |
Public on Aug 11, 2022 |
| Title |
Precise genomic editing of a pathogenic RBM20 mutation rescues dilated cardiomyopathy |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mutations in RNA binding motif protein 20 (RBM20) are a common cause of dilated cardiomyopathy (DCM). Many RBM20 mutations cluster within an arginine/serine rich (RS-rich) domain, resulting in mis-localization of RBM20 to ribonucleoprotein granules within the cytoplasm, abnormal splicing of cardiac genes, and cardiomyocyte dysfunction. We used adenine base editing (ABE) and prime editing to correct pathogenic p.R634Q and p.R636S mutations in the RS-rich domain in human isogenic induced pluripotent stem cell-derived cardiomyocytes. We also created humanized Rbm20R636Q mutant mice, which succumbed to severe cardiac dysfunction, heart failure and premature death. Systemic delivery of ABE components by adeno-associated virus in these mice restored cardiac function and extended life span. These findings demonstrate the potential of precise correction of genetic mutations as a promising therapeutic approach for DCM.
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| Overall design |
We then performed gene expression profiling analysis using data obtained from RNA-seq of iPSC-derived cardiomyocytes and hearts from mice.
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| Contributor(s) |
Nishiyama T, Olson E |
| Citation(s) |
36417486 |
| |
| Submission date |
Aug 08, 2022 |
| Last update date |
May 03, 2023 |
| Contact name |
Jiwoong Kim |
| Organization name |
UT Southwestern Medical Center
|
| Street address |
5323 Harry Hines Blvd.
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| City |
Dallas |
| State/province |
Texas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (2) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA867480 |
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