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 A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

nachricht A New Discovery in the Fight against Cancer: Tumor Cells Switch to a Different Mode
29.04.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

Im Focus: Ultra-thin glass is up and coming

As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.

Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Winds a quarter the speed of light spotted leaving mysterious binary systems

29.04.2016 | Physics and Astronomy

Fiber optic biosensor-integrated microfluidic chip to detect glucose levels

29.04.2016 | Health and Medicine

A cell senses its own curves: New research from the MBL Whitman Center

29.04.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>