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An RNA-based platform to neutralize DNMT1 function AptaDiR is an innovative RNA-based platform to neutralize DNMT1 function

ABSTRACT: DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of demethylating drugs that act indiscriminately on the genome and come with a toll of high toxicity and low specificity. Aptamers are novel targeting molecules considered high affinity ligands. By conjugating, the RNA inherent ability of inhibiting DNMT1, to an RNA aptamer platform, we generated the first-of-its kind aptamers approach targeting and neutralizing DNMT1 function – the aptaDiR. Molecular modelling of RNA-DNMT1 interactions’ coupled with biochemical and cellular assays enabled identification and characterization of the aptaDiR. This novel RNA bio-drug blocks DNA methylation and impairs cancer cell viability. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved hypomethylating protocols which will greatly improve clinical intervention on DNA methylation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE154471 | GEO | 2022/11/23

REPOSITORIES: GEO

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