Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Using RNA interference to tune gene activity in stem cells

03.02.2003


New method for the study and treatment of disease



The application of RNA interference (RNAi) to the study of mammalian biology and disease has the potential to revolutionize biomedical research and speed the development of novel therapeutic strategies.

A series of studies by Greg Hannon at Cold Spring Harbor Laboratory (CSHL) have revealed a great deal of information about the mechanism of RNAi, as well as how RNAi can be adapted for use in medical research. These and other studies led Science to name discoveries concerning RNAi the "Breakthrough of the Year" for 2002 among all of the sciences.


Now, researchers at CSHL have shown that RNAi can be used to set the level of gene activity in stem cells on "low," "medium," or "high."

The new study indicates that stable suppression of deleterious genes by RNAi--in which adult stem cells are isolated, modified ex vivo, and then re-introduced into the affected individual--might be an effective strategy for treating human disease.

The study, published in the February issue of Nature Genetics, focussed on the role of a tumor suppressor gene called p53 in a mouse model of lymphoma.

In the mouse model, forced expression of the Myc oncogene in B-cells causes the mice to develop B-cell lymphomas by 4 to 6 months of age. The scientists, led by Greg Hannon and his CSHL colleague, Scott Lowe, knew that completely deleting the p53 gene causes lymphomas to develop much sooner, and in a more aggressive, highly-invasive form, than lymphomas that develop when the p53 gene is present.

To test the effect of decreasing p53 to particular levels via RNA interference, the scientists reconstituted the blood cells of mice by first irradiating the animals to destroy their endogenous, bone marrow supply of hematopoietic stem cells, and then injected the mice with a fresh supply of hematopoietic stem cells that had been engineered through RNAi to produce low, medium, or high levels of p53.

The study showed that establishing different levels of p53 in B-cells by RNAi produces distinct forms of lymphoma. Similar to lymphomas that form in the absence of p53, lymphomas that formed in mice with low p53 levels developed rapidly (reaching terminal stage after 66 days, on average), infiltrated lung, liver, and spleen tissues, and showed little apoptosis or "programmed cell death."

In contrast, lymphomas that formed in mice with intermediate p53 levels developed less rapidly (reaching terminal stage after 95 days, on average), did not infiltrate lung, liver, or spleen tissues, and showed high levels of apoptosis. In mice with high B-cell p53 levels, lymphomas did not develop at an accelerated rate, and these mice did not experience decreased survival rates compared to control mice.

The study illustrates the ease with which RNAi "gene knockdowns" can be used to create a full range of mild to severe phenotypes (something that geneticists dream about), as well as the potential of RNAi in developing stem cell-based and other therapeutic strategies.

Along with a recent study by Hannon and his colleagues that demonstrated germline transmission of RNAi, the current study establishes RNAi as a convenient alternative to traditional, laborious, and less flexible homologous recombination-based gene knockout strategies for studying the effects of reduced gene expression in a wide variety of settings.

Peter Sherwood | EurekAlert!
Further information:
http://www.cshl.org/

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>