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
Killer sea snail a target for new drugs
07.07.2015 | University of Queensland
First images of dolphin brain circuitry hint at how they sense sound
07.07.2015 | Emory Health Sciences
When a duck paddles across a pond or a supersonic plane flies through the sky, it leaves a wake in its path. Wakes occur whenever something is traveling...
Researchers explore ultrafast control of magnetism across interfaces: A new study discovers how the sudden excitation of lattice vibrations in a crystal can trigger a change of the magnetic properties of an atomically-thin layer that lies on its surface.
A research team, led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter at CFEL in Hamburg, the University of Oxford, and the...
Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.
The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...
New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions
A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...
25.06.2015 | Event News
16.06.2015 | Event News
11.06.2015 | Event News
07.07.2015 | Physics and Astronomy
07.07.2015 | Earth Sciences
07.07.2015 | Physics and Astronomy