Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Designer molecules correct RNA splicing defects: New strategy for treating many diseases

13.01.2003


With a high-tech fix for faulty cellular editing, scientists at Cold Spring Harbor Laboratory have moved a step closer to developing treatments for a host of diseases as diverse as breast cancer, muscular dystrophy, and cystic fibrosis.



Many human diseases have been linked to defects in a cellular editing process called pre-messenger RNA splicing. Adrian Krainer, a molecular biologist at Cold Spring Harbor Laboratory, has spent years investigating this complex editing process, which takes the information coded in genes and makes it available for building proteins. In a new study published in the journal Nature Structural Biology, Krainer’s team has devised a clever way to correct RNA splicing defects implicated in breast cancer and spinal muscular atrophy (a neurodegenerative disease). In principle, the technique could provide the ability to correct RNA splicing defects associated with any gene or disease.

For now, Krainer’s method has been shown to work under the simplest of conditions -- in test tubes with small segments of RNA. The next step is to adapt the technique for use in living cells. Still, "It’s a very promising approach," says molecular biologist Brenton Graveley, of the University of Connecticut Health Center. "There are a lot of hurdles to be overcome in terms of delivering the corrective molecules to the cells that need to be treated. But theoretically the exact same approach could be taken for any gene at all, and the list of genes that have defects at the level of RNA splicing is very long," says Graveley, who is familiar with the research but not involved in the study.


For cells to produce protein, DNA is first transcribed into pre-messenger RNA (RNA is a chemical cousin of DNA). Pre-messenger RNA is a "word-for-word" representation of a DNA sequence in the language of RNA. But for reasons that remain unclear to scientists, pre-messenger RNA molecules contain excess "words" that are removed by splicing to create mature messenger RNA (mRNA), the templates that cells use to make proteins. In many genetic diseases, gene mutations cause errors in the RNA splicing process. Improperly spliced mRNA molecules lead to the creation of altered proteins that cannot perform their duties properly, resulting in disease.

Gene mutations that alter pre-mRNA splicing frequently cause an important segment of the RNA to be skipped or left out of the mature mRNA. With this in mind, Krainer and colleague Luca Cartegni looked for ways to tell a cell to include a piece of RNA that is erroneously skipped. They took inspiration from natural proteins that guide which segments are included when the cell’s splicing machinery cuts up pre-mRNA and pastes only the important bits back together. One end of these guide proteins attaches to the pre-mRNA transcript. The other end recruits enzymes that carry out the actual cutting and pasting.

Krainer and Cartegni attached the recruiting portion of the guide protein to a synthetic molecule that can be programmed to bind to any piece of RNA according to its sequence. The researchers designed a batch of these molecules corresponding to a mutant form of the BRCA1 gene implicated in breast cancer. The designer molecules successfully caused the splicing machinery to include an important piece of BRCA1 mRNA that is usually skipped. Thus, the designer molecules corrected the splicing error, making a normal messenger RNA from a defective pre-messenger RNA transcript.

Next, the scientists turned their new technology loose on a mutant form of the SMN2 gene which is associated with the neurodegenerative disease spinal muscular atrophy (SMA). People afflicted with SMA generally possess both a fully defective SMN1 gene and one or more copies of the closely related SMN2 gene which, due to skipping of a particular segment during RNA splicing, is capable of producing only small amounts of normal mRNA. The severity of SMA symptoms could be relieved if a patient’s SMN2 gene could be coaxed into producing more normal mRNA by including the skipped RNA segment more often. Just as they corrected splicing defects of BRCA1 RNA, Krainer and Cartegni’s designer molecules also enhanced the production of properly spliced SMN2 RNA.

The scientists dubbed the method ESSENCE (which stands for Exon-Specific Splicing Enhancement by small Chimeric Effectors). The next step is to create ESSENCE designer splicing molecules that pass easily into cells and can home-in on the desired splicing targets. The new study establishes that if such molecules can be developed, they may ultimately prove useful for treating a great diversity of human disease.

Peter Sherwood | EurekAlert!

More articles from Life Sciences:

nachricht Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

nachricht Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>