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.
The researchers chose to use gold nanoparticles as their support and transport system. They attached three components to the nanoparticles’ surfaces: 1) RNAse A, a robust enzyme that nonspecifically cleaves single-stranded RNA; 2) DNA oligonucleotides with a sequence selected to specifically bind the mRNA to be taken out of circulation; 3) A ligand that is designed to pilot the nanocomplex to the target cells – tumor cells in this case. The scientists chose Cys-tag EGF, a ligand that binds to a growth-hormone receptor present in significantly elevated quantities in the cell membranes of many tumors.One important mechanism of multidrug resistance in tumor cells is the active expulsion of drugs by means of a special transport protein (Pgp). Administration of chemotherapy drugs triggers formation of a large number of these transporters, which effectively protect the tumor cells from the drugs.
In order to silence the gene that codes Pgp, the researchers incorporated DNA that recognizes the corresponding mRNA into the nanocomplexes.
They were thus able to observe cleavage of this mRNA, a reduction in the concentration of Pgp, and renewed sensitivity toward the chemotherapy drug doxorubicin in multidrug-resistant tumor cell lines. In addition to combating multidrug resistance, the new method should prove to be a generally useful approach for gene therapy.About the Author
Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201309985
Xiaoyuan Chen | Angewandte Chemie
Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society
Calcium may play a role in the development of Parkinson's disease
19.02.2018 | University of Cambridge
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
19.02.2018 | Information Technology
19.02.2018 | Ecology, The Environment and Conservation
19.02.2018 | Life Sciences