Therapeutics: SiRNAs jump the hurdle

摘要

The specific delivery of small interfering RNAs (siRNAs) to tumour cells, especially those that are disseminated, is a major hurdle for the development of these molecules as therapeutics. Yao et al. have shown that this is possible by delivering siRNAs with a fusion protein, which is comprised of a single-chain fragmented antibody (ScFv) that targets tumour cells and a positively charged peptide that binds RNA.The Polo-like kinase 1 (PLK1) serine/threonine kinase is over-expressed in several cancer types and can promote proliferation and survival of tumour cells. Specific delivery in vitro of an siRNA targeting PLK1 into ERBB2 (also known as HER2)-expressing breast cancer cell lines and cells derived from surgically removed breast tumours was accomplished using a protamine peptide fused to an ScFv that binds ERBB2 (F5-P). F5-P-mediated delivery of PLKl siRNAs effectively reduced PLK1 expression, and reduced proliferation and increased apoptosis of ERBB2~+ breast cancer cell lines and primary breast cancer cells in vitro. The expression of a PLK1 mutant that was unable to bind the PLK1 siRNA restored proliferation and prevented apoptosis, indicating that the observed effects are likely to be a direct result of PLK1 silencing.