Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Harnessing the power of CRISPR in space and time


Researchers in Vienna from Ulrich Elling’s laboratory at IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences – in collaboration with the Vienna BioCenter Core Facilities have developed a revolutionary CRISPR technology called “CRISPR-Switch”, which enables unprecedented control of the CRISPR technique in both space and time.

CRISPR/Cas9 technology is based on a modified version of a bacterial defense system against bacteriophages. One of the landmark discoveries for this technique in fact was laid in Vienna and published in 2012 in a study co-authored by Emmanuelle Charpentier and VBC PhD student, Krzysztof Chylinski. Due to its power to also edit mammalian genomes, CRISPR/Cas9 has rapidly established itself as the most employed gene editing method in laboratories across the world with huge potential to find its way to the clinics to cure rare disease. Just a week ago, the first success in the treatment of sickle cell anemia was announced.

CRISPR-Switch technology.

©IMBA/Kaminski Grafik

To control the power of genome editing, several groups have worked on systems to control editing activity. Scientists from the lab of Ulrich Elling at IMBA were now able to gain unprecedented control over sgRNA activity, in a system termed “CRISPR-Switch”. The results are published in the renowned journal Nature Communications.

The CRISPR-Switch system radically amplifies the application potential of CRISPR-based gene editing, as it can be rapidly switched on without any detectable leakiness. It also circumvents possible immune responses in vivo, as it is not based on the modulation of Cas9 expression as previous methods were.
In CRISPR-Switch from the Elling lab, gene editing is achieved by modulating sgRNA expression, using a system based on Cre-Lox and Flp-FRT recombinases. These are site-specific recombination systems, which allow a precise location and timing of gene expression. Cre and Flp are known for their high recombination efficiency in different cell types, as well as their precision.

By using the novel CRISPR-Switch method, scientists are able to target genes with superior specificity, and, due to the use of recombinases, a gene can be knocked out in one chosen cell type precisely. As additional level of control, multiple genes can now be knocked out in any desirable order. This allows for unprecedented versatility in the CRISPR technique, as the exact timing of gene activation can be studied in different pathologies both in vivo and in vitro. Together with IMBA Alumnus Daniel Schramek from the Lunenfeld-Tanenbaum Research Institute in Toronto, the authors studied the order of mutagenic events that would result in glioma formation in mouse models. The CRISPR-Switch method is versatile and can be applied to different tumor types thus detecting the exact sequence of genes needed to induce tumor formation. What bears incredible potential is that with this technique, not only tumor initiation can be studied, but also the very challenging topic of tumor maintenance can be tackled.
The shared-first author of the study, Maria Hubmann, explains: “Our in vivo studies in mice confirmed that an explicit order of gene knockout was necessary for tumor formation. We looked at two specific genes, NF1 and TRP53, which are known to have a strong link to glioblastoma. Only when we knocked out TRP53 before NF1, and not vice versa, the mice developed gliomas”.

“CRISPR-Switch allows us to control gene editing in space and time, while ensuring an incredibly rapid on/off switch and with minimal unspecific effects. I am excited about the future applications of our method, as I am sure labs all over the world will soon find its benefits,” explains Krzysztof Chylinski, shared-first author from the Vienna BioCenter Core Facilities.

The CRISPR-Switch technology is also available as a partnering opportunity. IMBA is actively seeking for licensing partners with business interests in relevant areas of application, i.e. screening, mutation analysis, safer genome editing, multiplexing and/or somatic gene therapy.

Original publication:
Krzysztof Chylinski and Maria Hubmann, Ruth E. Hanna, Connor Yanchus, Georg Michlits, Esther C. H. Uijttewaal, John Doench, Daniel Schramek, Ulrich Elling
“CRISPR-Switch regulates sgRNA activity by Cre recombination for sequential editing of two loci”, Nature Communications, DOI 10.1038/s41467-019-13403-y

About IMBA
IMBA - Institute of Molecular Biotechnology - is one of the leading biomedical research institutes in Europe focusing on cutting-edge stem cell technologies, functional genomics, and RNA biology. IMBA is located at the Vienna BioCenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research. The stem cell and organoid research at IMBA is being funded by the Austrian Federal Ministry of Science and the City of Vienna.

About the Vienna BioCenter
Vienna BioCenter is a leading life sciences location in Europe, offering a unique combination of research, education and companies on a single campus: 1,800 employees, 1,500 students, 96 research groups, and 25 biotech companies. Scientists from 70 countries create a highly dynamic environment of international standards.


Caterina Purini, MSc. | idw - Informationsdienst Wissenschaft
Further information:

Further reports about: CRISPR Cas9 IMBA Molekulare Biotechnologie genes tumor formation

More articles from Life Sciences:

nachricht New portable tool analyzes microbes in the environment
27.01.2020 | Rutgers University

nachricht Cucumber, courgette and pumpkin under threat – first evidence of cucumber virus in Germany
27.01.2020 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen 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: Integrate Micro Chips for electronic Skin

Researchers from Dresden and Osaka present the first fully integrated flexible electronics made of magnetic sensors and organic circuits which opens the path towards the development of electronic skin.

Human skin is a fascinating and multifunctional organ with unique properties originating from its flexible and compliant nature. It allows for interfacing with...

Im Focus: Dresden researchers discover resistance mechanism in aggressive cancer

Protease blocks guardian function against uncontrolled cell division

Researchers of the Carl Gustav Carus University Hospital Dresden at the National Center for Tumor Diseases Dresden (NCT/UCC), together with an international...

Im Focus: New roles found for Huntington's disease protein

Crucial role in synapse formation could be new avenue toward treatment

A Duke University research team has identified a new function of a gene called huntingtin, a mutation of which underlies the progressive neurodegenerative...

Im Focus: A new look at 'strange metals'

For years, a new synthesis method has been developed at TU Wien (Vienna) to unlock the secrets of "strange metals". Now a breakthrough has been achieved. The results have been published in "Science".

Superconductors allow electrical current to flow without any resistance - but only below a certain critical temperature. Many materials have to be cooled down...

Im Focus: Programmable nests for cells

KIT researchers develop novel composites of DNA, silica particles, and carbon nanotubes -- Properties can be tailored to various applications

Using DNA, smallest silica particles, and carbon nanotubes, researchers of Karlsruhe Institute of Technology (KIT) developed novel programmable materials....

All Focus news of the innovation-report >>>



Industry & Economy
Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

„Advanced Battery Power“- Conference, Contributions are welcome!

07.01.2020 | Event News

Latest News

Dance of the honey bee reveals fondness for strawberries

27.01.2020 | Agricultural and Forestry Science

MTU engineers examine lithium battery defects

27.01.2020 | Power and Electrical Engineering

Quantum physics: On the way to quantum networks

27.01.2020 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>