Myotonic dystrophy type 1 (DM1) is the most common form of adult muscular dystrophy. Characterized by life-threatening muscle weakness, compromised respiration, and often cardiac conduction abnormalities, DM1 has high unmet medical need. DM1 is caused by a CTG repeat expansion in the 3ʹ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene which causes aggregation of DMPK mRNA hairpin structures as insoluble ribonuclear foci and sequestration of several RNA-binding proteins. Sequestration of key splicing regulators such as muscleblind like splicing regulator 1 (MBNL-1) drives aberrant splicing of hundreds of downstream transcripts. These splicing defects are thought to be a key driver of DM1 disease pathogenesis. We have developed a novel myotropic delivery platform comprising a myotropic AAV capsid and a promoter with strong activity in all muscle cells. We tested the ability of this novel platform to deliver a DMPK-targeting miRNA (AAV-amiRDMPK) and correct DM1-associated splicing defects. First, we treated immortalized human DM1 myotubes with AAV-amiRDMPK and analyzed the splicing profile of 36 genes previously shown to be affected in DM1 by NanoString analysis. Here, we observed significant splicing improvement for a subset of the 36 genes (MBNL1, GOLGA4, SOS1, CLASP1, zTTN and PKM). Subsequently, we performed splicing analysis of cardiac and skeletal muscles of a mouse model of DM1 (DMSXL mice), treated with a single intravenous dose of AAV-amiRDMPK, and we showed that treatment resulted in improved splicing in both tissues. Together, our data demonstrate that our novel myotropic delivery platform can improve a key marker of the disease in the cellular and animal models of DM1.