Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


A new way to model cancer


New gene-editing technique allows scientists to more rapidly study the role of mutations in tumor development.

Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer. One way to discover the role of these mutations is to breed a strain of mice that carry the genetic flaw — but breeding such mice is an expensive, time-consuming process.

Image: Thinkstock

Now, MIT researchers have found an alternative: They have shown that a gene-editing system called CRISPR can introduce cancer-causing mutations into the livers of adult mice, enabling scientists to screen these mutations much more quickly.

In a study appearing in the Aug. 6 issue of Nature, the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten. They are now working on ways to deliver the necessary CRISPR components to other organs, allowing them to investigate mutations found in other types of cancer.

... more about:
»CRISPR »Cancer »Cas9 »DNA »function »genes »liver »mutations »organs »p53 »tumors

“The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations. The flexibility of this technology, as delivery gets better in the future, will give you a way to pretty rapidly test those combinations,” says Institute Professor Phillip Sharp, an author of the paper.

Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology, is the paper’s senior author. The lead authors are Koch Institute postdocs Wen Xue, Sidi Chen, and Hao Yin.

Gene disruption

CRISPR relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this bacterial system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

In some cases, the researchers simply snip out part of a gene to disrupt its function; in others, they also introduce a DNA template strand that encodes a new sequence to replace the deleted DNA.

To investigate the potential usefulness of CRISPR for creating mouse models of cancer, the researchers first used it to knock out p53 and pten, which protect cells from becoming cancerous by regulating cell growth. Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.

Studies of such genetically engineered mice have yielded many important discoveries, but the process, which requires introducing mutations into embryonic stem cells, can take more than a year and costs hundreds of thousands of dollars. “It’s a very long process, and the more genes you’re working with, the longer and more complicated it becomes,” Jacks says.

Using Cas enzymes targeted to cut snippets of p53 and pten, the researchers were able to disrupt those two genes in about 3 percent of liver cells, enough to produce liver tumors within three months.

Many models possible

The researchers also used CRISPR to create a mouse model with an oncogene called beta catenin, which makes cells more likely to become cancerous if additional mutations occur later on. To create this model, the researchers had to cut out the normal version of the gene and replace it with an overactive form, which was successful in about 0.5 percent of hepatocytes (the cells that make up most of the liver).

The ability to not only delete genes, but also to replace them with altered versions “really opens up all sorts of new possibilities when you think about the kinds of genes that you would want to mutate in the future,” Jacks says. “Both loss of function and gain of function are possible.”

Using CRISPR to generate tumors should allow scientists to more rapidly study how different genetic mutations interact to produce cancers, as well as the effects of potential drugs on tumors with a specific genetic profile.

“This is a game-changer for the production of engineered strains of human cancer,” says Ronald DePinho, director of the University of Texas MD Anderson Cancer Center, who was not part of the research team. “CRISPR/Cas9 offers the ability to totally ablate gene function in adult mice. Enhanced potential of this powerful technology will be realized with improved delivery methods, the testing of CRISPR/Cas9 efficiency in other organs and tissues, and the use of CRISPR/Cas9 in tumor-prone backgrounds.”

In this study, the researchers delivered the genes necessary for CRISPR through injections into veins in the tails of the mice. While this is an effective way to get genetic material to the liver, it would not work for other organs of interest. However, nanoparticles and other delivery methods now being developed for DNA and RNA could prove more effective in targeting other organs, Sharp says.

The research was funded by the National Institutes of Health and the National Cancer Institute.

Sarah McDonnell | Eurek Alert!
Further information:

Further reports about: CRISPR Cancer Cas9 DNA function genes liver mutations organs p53 tumors

More articles from Life Sciences:

nachricht Tissue-engineered colon from human cells develop different types of neurons
02.10.2015 | Children's Hospital Los Angeles

nachricht Big eyes! – MDC Researchers Identify Cause of Inherited Form of Extreme Nearsightedness
02.10.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New Sinumerik features improve productivity and precision

EMO 2015, Hall 3, Booth E06/F03

  • Drive optimization called automatically by the part program boosts productivity
  • Automatically switching the dynamic values to rapid traverse and interpolation...

Im Focus: LZH presents additive manufacturing at the LABVOLUTION

The Laser Zentrum Hannover e.V. (LZH) will present how laser-based technologies can contribute to the laboratory of the future at the LABVOLUTION in Hannover in Hall 9, Stand E67/09, from October 6th to 8th, 2015. As a part of the model lab smartLAB, the LZH is showing how additive manufacturing, better known as 3-D printing, can make experimental setups more flexible.

Twelve partners from science and industry are presenting an intelligent and innovative model lab at the special display smartLAB. A part of this intelligent...

Im Focus: New polymer creates safer fuels

Before embarking on a transcontinental journey, jet airplanes fill up with tens of thousands of gallons of fuel. In the event of a crash, such large quantities of fuel increase the severity of an explosion upon impact.

Researchers at Caltech and JPL have discovered a polymeric fuel additive that can reduce the intensity of postimpact explosions that occur during accidents and...

Im Focus: 3-D printing techniques help surgeons carve new ears

When surgical residents need to practice a complicated procedure to fashion a new ear for children without one, they typically get a bar of soap, carrot or an apple.

To treat children with a missing or under-developed ear, experienced surgeons harvest pieces of rib cartilage from the child and carve them into the framework...

Im Focus: Walk the line

NASA studies physical performance after spaceflight

Walking an obstacle course on Earth is relatively easy. Walking an obstacle course on Earth after being in space for six months is not quite as simple. The...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Infrared thermography can detect joint inflammation and help improving work ergonomics

02.10.2015 | Medical Engineering

Semiconductor nanoparticles show high luminescence in a polymer matrix

02.10.2015 | Materials Sciences

New Sinumerik features improve productivity and precision

02.10.2015 | Trade Fair News

More VideoLinks >>>