A new gene silencing platform -- silence is golden

Feb 08, 2009

A team of researchers led by Rutgers' Samuel Gunderson has developed a novel gene silencing platform with very significant improvements over existing RNAi approaches. This may enable the development and discovery of a new class of drugs to treat a wide array of diseases. Critical to the technology is the approach this team took to specifically target RNA biosynthesis.

The research findings are reported in the journal Nature Biotechnology, published online in the February 8th issue.

Gunderson, an associate professor in the Department of Molecular Biology and Biochemistry at Rutgers, The State University of New Jersey, has created highly efficient gene silencing agents that function via a novel mechanism of action. The agents are single-stranded oligonucleotides, called U1 Adaptors, that have dual, and independent, functions. First is a target-gene binding domain that can be tailored to any gene. The second domain inhibits mRNA maturation by binding U1 snRNP, a component of the cellular splicing apparatus.

By combining both capabilities in the same molecule, the U1 Adaptor can inhibit the pre-mRNA maturation step of polyA tail addition in a gene specific manner. Further, the domains of the oligonucleotide are independent so transcript binding and U1 snRNP binding can be independently optimized and adapted to a wide array of genes associated with disease.

"The U1 Adaptor platform expands on early technologies that used 5'-end-mutated U1 snRNA," Gunderson explained. "The U1 Adaptor is an oligonucleotide version of this older method and instead targets the 3' end processing step. U1 Adaptors have high activity when used alone and are synergistic when used in combination with RNAi." Gunderson went on to say that the range of possible targets is very broad due to the mechanism of action in which inhibition occurs during the biosynthesis of mRNA at the near universal 3' end processing step. Perhaps the most interesting aspect of this technology is that U1 Adaptors can possibly inhibit genes that do not respond to current RNAi methods.

The applications of U1 Adaptors expand on those currently available using standard RNAi approaches. They can be used as a research tool to determine gene function and to validate gene targets. Gene silencing molecules also have potential prophylactic and therapeutic applications based upon ongoing clinical trials using RNAi and traditional antisense approaches. For some genes that cause disease, these other approaches may not be effective enough and U1 Adaptors may provide a novel solution.'

Source: Rutgers University

Explore further: Honey bees sting Texas man about 1,000 times

add to favorites email to friend print save as pdf

Related Stories

Advancing medicine, layer by layer

Jul 02, 2014

Personalized cancer treatments and better bone implants could grow from techniques demonstrated by graduate students Stephen W. Morton and Nisarg J. Shah, who are both working in chemical engineering professor ...

New technology detect cellular memory

Feb 24, 2014

Cells in our body are constantly dividing to maintain our body functions. At each division, our DNA code and a whole machinery of supporting components has to be faithfully duplicated to maintain the cell's ...

Recommended for you

Study indicates large raptors in Africa used for bushmeat

13 hours ago

Bushmeat, the use of native animal species for food or commercial food sale, has been heavily documented to be a significant factor in the decline of many species of primates and other mammals. However, a new study indicates ...

The microbes make the sake brewery

14 hours ago

A sake brewery has its own microbial terroir, meaning the microbial populations found on surfaces in the facility resemble those found in the product, creating the final flavor according to research published ahead of print ...

Fighting bacteria—with viruses

15 hours ago

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

NeilFarbstein
1 / 5 (1) Feb 08, 2009
I worked on this same concept years ago. One downside is that the SNURP machinery of human cells will be tied up by artificial RNA fragments that will slow down the vital RNA intron editing functions. There are limits to its' effectiveness before toxic effects will occur.
HTTP://VULVOX.TRIPOD.COM