Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene editing technique helps find cancer's weak spots

21.03.2017

Genetic mutations that cause cancer also weaken cancer cells, creating an opportunity for researchers to develop drugs that will selectively kill them, while sparing normal cells. This concept is called "synthetic lethality" because the drug is only lethal to mutated (synthetic) cells. Researchers at UC San Diego School of Medicine and Jacobs School of Engineering developed a new method to search for synthetic-lethal gene combinations.

The technique, published March 20 in Nature Methods, uncovered 120 new opportunities for cancer drug development.


This is a network of synthetic-lethal interactions connecting commonly mutated genes to potential drug targets.

Credit: UC San Diego Health

"The ovarian cancer drug olaparib works by synthetic lethality -- it inhibits a gene that, when a BRCA gene is also mutated, kills just those cancer cells," said John Paul Shen, MD, clinical instructor and postdoctoral fellow at UC San Diego School of Medicine and Moores Cancer Center.

"Many other cancers could likely be treated this way as well, but we don't yet know which gene mutation combinations will be synthetic-lethal." Shen was co-first author of the study, along with Dongxin Zhao, PhD, postdoctoral fellow at UC San Diego Jacobs School of Engineering, and Roman Sasik, PhD, computational biologist in the UC San Diego School of Medicine.

To overcome this limitation, the team developed a new method that uses the gene editing technique CRISPR/Cas9 to simultaneously test for thousands of synthetic-lethal interactions. CRISPR/Cas9 works like this: researchers design a "guide" RNA to match the sequence of a specific target gene in a cell. The RNA guides the Cas9 enzyme to the desired spot, where it cuts the DNA. The cell can repair the DNA break, but it does so imprecisely, thereby inactivating the gene.

In this study, the researchers designed a CRISPR/Cas9 system with two guide RNAs: 1) one that targets a tumor suppressor gene that is commonly mutated in cancer and 2) one that targets a gene that could also be disrupted by a cancer drug. They deployed this system against 73 genes in three laboratory cell lines -- human cervical cancer, lung cancer and embryonic kidney cells -- for a total of 150,000 gene combinations. Then they measured cell growth and death.

The approach revealed more than 120 new synthetic-lethal interactions.

"Identifying underlying genetic interactions in this way can reveal important functional relationships between genes, such as contributions to the same protein complex or pathway," co-senior author Trey Ideker, PhD, professor in the UC San Diego School of Medicine, founder of the UC San Diego Center for Computational Biology and Bioinformatics and co-director of the Cancer Cell Map Initiative. "This in turn can impact both our fundamental understanding of biological systems, as well as therapeutics development."

Many of the gene interactions the team identified were synthetic-lethal in just one of the three cell lines tested. This means that synthetic-lethal interactions may be different in different types of cancer. The researchers said this will be an important consideration for future drug development.

"Moving forward, we intend to further refine our technology platform and make it more robust," said co-senior author Prashant Mali, PhD, assistant professor in the Jacobs School of Engineering at UC San Diego. "And we are scaling our cancer genetic networks maps so we can systematically identify new combination therapies."

###

Additional study co-authors include: Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex Beckett, Kyle Sanchez, Alex Thomas, Chih-Chung Kuo, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, UC San Diego; Dan Du, Assen Roguev, Nevan Krogan, UC San Francisco; and Lei Qi, Stanford University.

Media Contact

Heather Buschman
hbuschman@ucsd.edu
858-249-0456

 @UCSanDiego

http://www.ucsd.edu 

Heather Buschman | EurekAlert!

Further reports about: CANCER CRISPR DNA RNA cancer drug cancer drug development embryonic kidney cells

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: BAM@Hannover Messe: innovative 3D printing method for space flight

At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.

Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...

Im Focus: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Getting electrons to move in a semiconductor

25.04.2018 | Physics and Astronomy

Reconstructing what makes us tick

25.04.2018 | Physics and Astronomy

Cheap 3-D printer can produce self-folding materials

25.04.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>