PMC:5985359 / 41095-42233 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/5985359","sourcedb":"PMC","sourceid":"5985359","source_url":"https://www.ncbi.nlm.nih.gov/pmc/5985359","text":"Importantly, we demonstrate here that an ASO targeted to the CTG trinucleotide TCF4 expansion can ameliorate disease-associated markers of RNA toxicity in CECs derived from FECD-affected subjects, specifically reducing RNA foci formation (Figures 5A–5C), prompting MBNL1 nuclear redistribution (Figures 5D and 5E) and partially suppressing differential splicing events (Figure 6). We additionally demonstrate that the ASO can access the corneal endothelium when injected intravitreally in mice (Figure S6). Entry of fluorescently labeled ASO to the corneal endothelial cells is an endogenous property of naked 2′Ome-PS-ASOs oligo and no other excipients are required to induce entry into these cells. Access to the CECs is also both dose and time dependent, suggesting that ASOs are rapidly taken up by cells after dosing. While it may be desirable to consider a topical eye drop therapy for FECD using an ASO approach, this is highly unlikely to be effective using naked ASOs given the structure of the corneal epithelium and the size and charge of ASOs; an adjunctive delivery technology would likely have to be considered in this case.","tracks":[]}