Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Silenced - Overcoming multidrug resistance in cancer cells by silencing genes with RNA

22.01.2014
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.

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
Dr. Xiaoyuan (Shawn) Chen is Senior Investigator and Chief of the Laboratory of Molecular Imaging and Nanomedicine (LOMIN) at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. His aims are to develop molecular imaging toolbox for better understanding of biology, early diagnosis of disease, monitoring therapy response, and guiding drug discovery/development. His lab puts special emphasis on high-sensitivity nanosensors for biomarker detection and theranostic nanomedicine for imaging, and gene and drug delivery.
Author: Xiaoyuan Chen, National Institutes of Health (NIH), Bethesda (USA), http://www.nibib.nih.gov/about-nibib/staff/xiaoyuan-shawn-chen
Title: Biomimetic RNA-Silencing Nanocomplexes: Overcoming Multidrug Resistance in Cancer Cells

Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201309985

Xiaoyuan Chen | Angewandte Chemie
Further information:
http://pressroom.angewandte.org

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>