Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tool developed to silence genes in specific tissues using RNAi

16.01.2006


Researchers at The University of Texas M. D. Anderson Cancer Center say they have jumped a significant hurdle in the use of RNA interference (RNAi), believed by many to be the ultimate tool to both decode the function of individual genes in the human genome and to treat disease.



Reporting in the journal Genes and Development, investigators have developed a simple way to use the RNAi approach to silence a selected gene in a specific tissue in a mouse to determine the function of that targeted gene.

Previously reported approaches to achieve this were either technically cumbersome, not generally applicable, or only achieved transient knockdown of the target gene.


"Having a tool that will allow us to knockdown the expression of any given gene in any specific tissue or cell type represents a significant advance in the field," says the study’s lead investigator, Miles Wilkinson, Ph.D., a professor in the Department of Immunology.

For example, this method could potentially be used in humans "to knockdown the expression of mutant or overexpressed genes that cause human diseases, including cancer," Wilkinson says. "Scientists and clinicians can use it to reduce the expression of the target gene in a single or limited numbers of cell types or tissues, thereby reducing side effects."

Equally, the technique can help researchers determine the function of a single gene in a single tissue, which "is potentially a powerful investigative tool," Wilkinson says. "By silencing a particular gene in a specific tissue, you can learn what the function of that gene is in that particular tissue without blocking its essential functions in other tissues."

In their study, Wilkinson and his research team demonstrated how well their tool worked by silencing the WT1 tumor suppressor gene in the testes of mice. They found this gene is important in the production of healthy sperm by encoding a regulatory protein called a transcription factor that controls the formation of adherens junctions, or the cell-to-cell contacts between nurse cells and the germ cells that ultimately become sperm.

Using RNAi to silence WT1, therefore, led to the discovery that WT1 is the first transcription factor shown to regulate the formations of these junctions, Wilkinson says. "It is a transcription factor that dictates both the formation of the testes in the embryo, and the function of the testes after birth."

Researchers worldwide have been trying to harness the power of RNAi since it was discovered in 1998. RNAi rocked the world of science because of the vast implications this natural cellular control system potentially offered medicine.

RNAi is used by cells in many life forms to identify viral RNA, which often enters a cell as a double strand. The organism’s own RNA, however, leaves the nucleus of cells (where it was produced by DNA) as a single strand, to be decoded by ribosomes into the proteins that perform all the work of the cell. RNAi, therefore, recognizes the double strand of viral RNA as different, and sets in motion cell machinery that destroys the invading RNA. This involves cutting up the double-stranded RNA, separating it into single strands, and destroying other single-stranded RNA molecules that are complementary to those small RNA segments.

Scientists quickly realized that if they could produce a double-stranded RNA that mimics the RNA produced by a gene they wish to silence, RNAi would do the job for them. Producing the decoy "small RNAs" that trigger RNAi has become a fairly simple process, Wilkinson says, but the difficulty has been to use these matches only in specific tissues, and to figure out a way to make this "treatment" last. The work by the M. D. Anderson team has come up with a solution that solves both problems.

The technique they developed involves use of two different "modules" that can be swapped in and out of the backbone of a vector. One is a small stem loop designed to complement the RNA produced by the gene they wish to silence, and the other is a "promoter" that provides expression specific to the tissue they want to target. "There are whole batteries of different promoters, ones specifically for skin, or different parts of the brain, or whatever organ or tissue you are likely to want," Wilkinson says. "By swapping out either of these modules, you have the potential to silence any gene in any tissue you might want," he said.

In their study, the researchers made a vector with a promoter specific for nurse cells in the testis, so that the small RNA that is associated with WT1 is only made in this cell type, thereby reducing WT1 levels that are only in the nurse cells. Other organs, like kidney, that need WT1 to function are not affected, Wilkinson says.

"We are very excited about the potential of this approach, and hope that is solves what had become a significant roadblock to effective use of RNAi," he says.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History

nachricht New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

Im Focus: Autonomous 3D scanner supports individual manufacturing processes

Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).

Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Fingerprints of quantum entanglement

16.02.2018 | Information Technology

'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers

16.02.2018 | Health and Medicine

Hubble sees Neptune's mysterious shrinking storm

16.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>