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Antitumor efficacy of sequence specific DNA-targeted gamma PNA based cMyc inhibitor

ABSTRACT: Targeting oncogenes at the genomic DNA level can open new avenues for precision medicine. Significant efforts are ongoing to target oncogenes using diverse RNA-targeted and protein-targeted platforms, but no progress has been made to target genomic DNA for cancer therapy. Here, we introduce a gamma peptide nucleic acid (PNA)-based genomic DNA-targeted platform to silence oncogenes in vivo. gPNAs can efficiently invade the mixed sequences of genomic DNA with high affinity and specificity. As a proof-of-concept, we established that gPNA could inhibit c-Myc transcription in multiple cell lines. In vivo efficacy and safety of the DNA-targeted approach were demonstrated in three pre-clinical models. We also established that anti-transcription gPNA in combination with histone deacetylase inhibitors (HDACi) and chemotherapeutic drugs results in high and robust antitumor activity in cell-line and patient-derived xenografts. Overall, this strategy offers a unique therapeutic platform to target genomic DNA to inhibit oncogenes for cancer therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246439 | GEO | 2023/11/16

REPOSITORIES: GEO

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