Introduction

The invention relates to novel RNA nucleic acids (aptamers) capable of inhibiting DNA methyltransferase 1 (DNMT1), enzyme involved in DNA methylation, strictly linked to tumorogenesis. The invention therefore claims the use of such aptamers for treatment of neoplastic diseases.

Technical features

DNA methylation is a key epigenetic signature implicated in the regulation of gene expression. Several studies have established a link between aberrant promoter DNA methylation and cancer. There is a need to provide specific and effective inhibitors againts DNA methiltrasferases and to develop clinically relevant strategies for cancer therapy. So far, there are only two compounds approved by the FDA able to inhibit global DNA methylation, but they are poorly selective and exhibit high instability and toxicity. Aptamers are small oligonucleotides showing high affinity and specificity and many advantages as therapeutic tools. Our inventors have isolated anti-DNMT1 RNA aptamers with the ability of highly specific inhibition of DNA methylation, high stability, and the reduction of cellular vitality, proving to be effective and innovative for the treatment of cancers, also when loaded onto nanostructures for targeted delivery.

Possible Applications

• Therapeutic approach towards neoplastic diseases;
• Possible development of nanostructures containing anti DNMT1 aptamers and other aptameric molecules able to recognize neoplastic cells and allow the release of inhibitors to tumor cells.

Advantages

• High affinity and specificity;
• High Stability: they are very resistant to degradation in serum (more than 48 hours);
• Low batch variability;
• Simple production, easy modification and cost effectiveness;
• Safety: no toxicity and immunogenicity, suitable for repeated administrations.