Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Transcriptional Gene Silencing in Nucleus Shown

09.08.2004


A new gene-silencing technique that takes place in the nucleus of human cells, has been demonstrated by researchers at the University of California, San Diego (UCSD) School of Medicine and the VA San Diego Healthcare System. The technique, called transcriptional gene silencing (TGS), provides a new research tool to study gene function and, if continuing studies prove the concept, it could potentially become a method for therapeutic modification or the expression of disease-producing genes.



Selected for speedy publication in the August 5, 2004 edition of Science Express, the study describes, for the first time, the ability to shut down a gene literally before it is born in the nucleus of a cell. The benefit over previous gene-silencing techniques is that the nuclear version may have the potential to last considerably longer than current methods that act in the cytoplasm, the cellular area outside the nucleus.

The new technique, and older gene-silencing methods that have given rise in recent years to a multi-million dollar pharmaceutical industry, utilizes ribonucleic acid (RNA), the cousin of DNA. Specifically, researchers use synthetic, short pieces of RNA called short interfering RNA (siRNA), to shut down genes. The synthetic versions are patterned after naturally occurring siRNA in the body that may act as a defense against gene sequences that come from viruses or other genetic parasites.


The study’s senior author, David J. Looney, M.D., associate professor of medicine at UCSD and the VA San Diego Healthcare System, said the new technique provides a new tool for research investigation aimed at elucidating the effects of different genes, and has the potential to modify gene expression in disease, such as knocking out expression of genes required for tumor growth. He cautioned, however, that further studies are needed to prove the general applicability of this concept.

An understanding of siRNA begins with a look at theway by which genes work. First, a “promoter” region within the gene must be active in order to allow the genetic information encoded in the DNA to be copied (transcribed) into a single strand of RNA called messenger RNA (mRNA). During normal transcription, the mRNA leaves the nucleus and travels to the cytoplasm of the cell, where it works with another cellular component called the ribosome to make proteins.

Technology developed about four years ago introduced synthetic siRNA into the cytoplasm of cells to silence specific genes. This technique was called post-transcriptional gene silencing (PTGS). However, PTGS is transient, with siRNA lasting only a few days in the cytoplasm. Although this is enough time for short-term research projects, the use of siRNA for therapeutic applications, such as treatment for viral infections like HIV, probably require multiple siRNA treatments or the use of a gene therapy approach.

UCSD researchers used either lentiviral vectors (molecular ferries) to open up the nuclear membrane, or special transfection reagents which direct the transfected synthetic siRNA to the nucleus. This allowed siRNA access to the promoter, where it stopped the first part of the gene-making process called transcription, before it began. Previous research with siRNA used in the nucleus of plants has indicated that this effect can be long lasting, giving rise to the hope that it will be similarly long lasting in humans. Until now, however, scientists have been unable to detect activity of siRNA directed against gene promoters in the nucleus of human cells.

Kevin V. Morris, Ph.D., the study’s first author and a post-doctoral fellow in Looney’s lab, noted that “theoretically, one could envision targeting virtually any gene at the level of the promoter and silencing that gene. This has implications in most biological processes in which one would want to down regulate the expression of a gene, such as those genes involved in virus infections such as HIV, as well as human cancers and certain genetic disorders.”

In continuing studies, the Looney lab and others in the country will investigate this new method’s persistence within the human-cell nucleus, its successful targeting of human promoters, and whether it is feasible to use this technique to inhibit HIV or other viruses.

In addition to Looney and Morris, the authors were Simon W.-L. Chan, Ph.D., UCLA Department of Molecular, Cell and Developmental Biology; and Steven E. Jacobsen, Ph.D., UCLA Department of Molecular, Cell and Developmental Biology, and the UCLA Molecular Biology Institute.

The study was supported by the National Institutes of Health.

| newswise
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Cells communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

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...

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

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>