Overcoming multidrug resistance in cancer cells by silencing genes with RNA

Resistance of tumor cells toward multiple cytostatic drugs is a serious problem in cancer treatment.

In the journal Angewandte Chemie, a team of Chinese and American researchers has now introduced a new approach to gene therapy that could counter this problem: The gene that codes for resistance is "silenced" through the use of an ingenious nanocomplex.

Every cell in our body contains our complete genetic information. However, not all genes are used in every cell at all times. Regulatory processes are needed to determine when a gene should be read and transcribed to messenger-RNA (mRNA), and the corresponding protein built.

One such mechanism is RNA silencing. In this mechanism, short, specific, silencing RNA (siRNA) fragments bind to the mRNA to be silenced with participation from several enzyme complexes. The enzymes cleave the mRNA, preventing its translation into a protein. Gene therapies based on synthetic siRNA are under clinical development.

However, these siRNA drugs are directed toward the cellular silencing "machinery" and may disrupt natural gene regulation pathways, which results in side effects. In addition, they require a transport system to carry them through the cell membrane and to protect them from rapid degradation. Led by Min Yang at the Jiangsu Institute of Nuclear Medicine (Wuxi, China) and Xiaoyuan Chen at the National Institutes of Health (Bethesda, USA), the researchers have now developed an alternative approach that doesn't have these disadvantages. It is based on a nanocomplex that already includes the required machinery and packaging.