Research ArticleCancer

Derepression of co-silenced tumor suppressor genes by nanoparticle-loaded circular ssDNA reduces tumor malignancy

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Science Translational Medicine  23 May 2018:
Vol. 10, Issue 442, eaao6321
DOI: 10.1126/scitranslmed.aao6321

Protecting tumor suppressors

Strategies to target inactive tumor suppressor genes in cancer lag behind advances in targeting oncogenes. In new work, Meng et al. developed a therapeutic strategy to simultaneously up-regulate three different tumor suppressor genes that are sometimes co-silenced in different cancers by a microRNA called miR-9. They created a circular single-stranded DNA (CSSD) containing sequences to bind miR-9, thus sequestering it away from its target tumor suppressor genes. Loading the CSSDs onto nanoparticles improved delivery into human tumor cells. The CSSD increased expression of the three tumor suppressor proteins and displayed an antitumor effect in both cell line–based ex vivo models and dozens of patient-derived xenografts in mice.

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