Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A Molecular Toolkit for Gene Silencing

13.12.2013
The team of Johannes Zuber at the IMP in Vienna, Austria, managed to overcome remaining key limitations of RNA interference (RNAi) - a unique method to specifically shut off genes.

By using an optimized design, the scientists were able to inhibit genes with greatly enhanced efficiency and accuracy. The new method facilitates the search for drug targets and improves the interpretation of experimental results.


RNA-interference: small RNA molecules suppress gene expression (artist’s interpretation). IMP

The IMP will make this „RNAi toolkit“ available to researchers. Results of the study are published in the current issue of Cell Reports.

RNA interference (RNAi) is a regulatory mechanism that occurs naturally within cells. Short pieces of RNA (so-called “hairpins”) interfere with transcribed genetic information to silence genes. RNAi was originally discovered in plants in 1990, and in 2001 was also found in mammals. Right from its discovery, RNAi has inspired scientists to utilize the new mechanism for the development of experimental gene suppression tools. Beyond many applications in basic biological research, RNAi has become a unique method to identify and study therapeutic target genes. However, despite their enormous potential, currently available RNAi reagents are often ineffective or come along with unspecific side-effects.

Inspired by nature

Johannes Zuber and his colleague Christof Fellmann came up with ideas how to improve RNAi technology back in 2010, when both were still working at Cold Spring Harbor Laboratory (CSHL) in the US. “The basic principles of RNAi are not yet fully understood. To shut off a specific gene, one has to test many hairpin molecules, and often only one out of ten will be effective enough. To improve the method, we took nature as an example,” Zuber explains their line of thought. He finally took the project to the IMP, while Fellmann continued his scientific career at Mirimus, a CSHL-based biotech company developing advanced RNAi technologies.

A particularly powerful and commonly used RNAi method is based on embedding synthetic hairpin sequences into naturally occurring „micro-RNA backbones“. The result is an RNA-construct that mimics nature and is processed by normal cellular pathways. However, the performance of existing reagents designed this way remains far from perfect.

Zuber and his team analyzed a human micro-RNA backbone, focusing on sequence parts that remained unchanged during evolution – a sign that they may have important functions. The scientists realized that some of these sequences had been altered in the commonly used synthetic RNAi backbone. By correcting these differences and systematically testing many design variants, Zuber and his team managed to greatly improve the effectiveness of the synthetic RNAi tool.

Upgrade from a Beetle to a Lamborghini

“The benefit for science is tremendous” Zuber points out the relevance of his results. While current methods involve testing up to twenty hairpins to strongly suppress a given gene, the optimized reagents cut down the number to an average of four. Moreover, in high-throughput screening studies it will be easier to nominate positive hits and interpret negative results.

“We are taking the technology from a molecular Beetle to a Lamborghini” Zuber draws an analogy. “The upgrade is simple and existing reagents can be adapted with minimal effort.” Zuber and his co-workers at the IMP provide the new method and reagents - an “entire toolbox for effective RNAi”, as he calls it - to the scientific community. Cooperation partners and colleagues at the IMP who have already tested these new reagents are fully convinced of the benefits.

Improvement for the search of new drugs

In the future, Zuber’s study will allow a better exploitation of the potential of RNAi in cancer research. Despite tremendous efforts, pharmaceutical companies have not yet managed to develop RNAi as a drug in humans. However, large-scale “RNAi screens” represent a unique procedure to find and test the most promising target genes for new drugs before launching the slow and expensive process of developing a new drug. The optimized RNAi reagents are especially useful for such high-throughput screens, as more genes can be tested simultaneously with higher efficiency and precision. And, most importantly, introduction of the optimized RNAi tools will reduce the risk of missing promising targets for future therapeutic use.

Original Publication
C. Fellmann, T. Hoffmann, V. Sridhar, B. Hopfgartner, M. Muhar, M. Roth, DY Lai, IAM Barbosa, JS Kwon, Y. Guan and J. Zuber: An optimized microRNA backbone for effective single-copy RNAi. Cell Reports 5: 1-10, December 16, 2013. http://dx.doi.org/10.1016/j.celrep.2013.11.020
Illustration
An illustration can be downloaded from the IMP Website and used free of charge in connection with this press release: http://www.imp.ac.at/pressefoto-RNAi
About the IMP
The Research Institute of Molecular Pathology (IMP) in Vienna is a basic biomedical research institute largely sponsored by Boehringer Ingelheim. With over 200 scientists from 30 nations, the IMP is committed to scientific discovery of fundamental molecular and cellular mechanisms underlying complex biological phenomena. Research areas include cell and molecular biology, neurobiology, disease mechanisms and computational biology.
About Johannes Zuber
Johannes Zuber is a Group Leader at the Research Institute of Molecular Pathology (IMP) in Vienna where he founded his own lab in 2011. Following his Medicine studies at the Humboldt University in Berlin and a thesis in basic cancer research, he did a four year clinical residency at the Department of Hematology and Oncology at the Charité University Hospital in Berlin, where acute leukemias became the focus of his clinical work and scientific interest. In 2005, he joined Scott Lowe’s lab at Cold Spring Harbor Laboratory (CSHL) as a postdoc, where in 2009 he became the CSHL Clinical Research Fellow. His scientific work focuses on the development and use of innovative RNAi technologies and cancer mouse models to systematically explore therapeutic targets in leukemias and other cancers. His most recent contributions to the discovery of BRD4 as new therapeutic target have been selected by Nature medicine as “Notable Advance in Cancer Research 2011”
About Christof Fellmann
Christof Fellmann is Chief Scientific Officer at Mirimus Inc., a Biotechnology Company developing advanced RNAi reagents for accelerated drug development. Following undergraduate training in Molecular Biology at the University of Basel, he received a Masters degree from the Ecole Supérieure de Biotechnologie Strasbourg. In 2007 he joined the laboratory of Scott Lowe at Cold Spring Harbor Laboratory (CSHL) as a PhD student, where he established a high-throughput “Sensor” assay for the functional optimization of RNAi triggers for large-scale loss-of-function screens and RNAi-based mouse models of human disease. While obtaining his doctorate from the University of Zurich, he co-founded Mirimus Inc. in 2010 to make optimized RNAi reagents available to the broader research community.
Press Contact
Dr. Heidemarie Hurtl
Communications Manager
IMP - Research Institute of Molecular Pathology
Dr. Bohr-Gasse 7
1030 Vienna, Austria
phone +43 (0)1 79730-3625
mobile: +43 (0)664 8247910
E-mail: hurtl@imp.ac.at
Scientific Contact:
zuber@imp.ac.at

Dr. Heidemarie Hurtl | idw
Further information:
http://www.imp.ac.at/news/press-releases/press-release/press-release-a-molecular-toolkit-for-gene-silencing/

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>