 |
|
A new gene silencing platform -- silence is golden
February 09, 2009Findings may lead to novel treatments for diseases resistant to current RNAi
NEW BRUNSWICK, N.J. - 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.'
Rutgers University
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.'
Rutgers University
Gene Silencing Current Events and Gene Silencing News RSSGene shut-down may offer early warning of chronic leukemia
A new study shows that certain genes are turned off early, before clinical signs of the disease appear, in the development of chronic leukemia.
Trojan horse for ovarian cancer -- nanoparticles turn immune system soldiers against tumor cells
In a feat of trickery, Dartmouth Medical School immunologists have devised a Trojan horse to help overcome ovarian cancer, unleashing a surprise killer in the surroundings of a hard-to-treat tumor.
MicroRNAs grease the cell's circadian clockwork
Most of our cells possess an internal clock, a group of genes displaying a cyclic expression pattern that reaches a peak once a day.
The future of personalized cancer treatment: An entirely new direction for RNAi delivery
In technology that promises to one day allow drug delivery to be tailored to an individual patient and a particular cancer tumor, researchers at the University of California, San Diego School of Medicine, have developed an efficient system for delivering siRNA into primary cells.
New nucleotide could revolutionize epigenetics
Anyone who studied a little genetics in high school has heard of adenine, thymine, guanine and cytosine -- the A,T,G and C that make up the DNA code.
New therapeutic strategy could target toxic protein in most patients with Huntington's disease
Howard Hughes Medical Institute researchers have designed tiny RNA molecules that shut off the gene that causes Huntington's disease without damaging that gene's healthy counterpart, which maintains the health and vitality of neurons.
A miR boost enables acute leukemia cells to mature
A new study by Ohio State University cancer researchers shows that boosting the level of a molecule called miR-29b in acute myeloid leukemia (AML) cells can reverse gene changes that trap the cells in an immature, fast growing state of development.
RNA research strategy for Europe takes shape
Research into RNA, a molecule found in every cell of our bodies, could lead to remarkable advances in the treatment of diseases such as cancer and diabetes, a meeting organised by the European Science Foundation was told.
200,000 rice mutants available worldwide for scientific investigation
Scientists across the world are building an extensive repository of genetically modified rice plants in the hope of understanding the function of the approximately 57,000 genes that make up the genome of Oryza sativa.
Plant polymerases IV and V are special forms of Polymerase II
It's a little like finding out that Superman is actually Clark Kent. A team of biologists at Washington University in St. Louis has discovered that two vital cellular components, nuclear RNA Polymerases IV and V (Pol IV and V), found only in plants, are actually specialized forms of RNA Polymerase II, an essential enzyme of all eukaryotic organisms, including humans.
More Gene Silencing Current Events and Gene Silencing News Articles
 |
Rnai: A Guide to Gene Silencing (Manual) by Gregory J. Hannon (Author), Gregory J. Hannon (Editor) The ability of double stranded RNA to inhibit the expression of genes with an appropriate sequence can be harnessed to silence target genes in vitro in a new and powerful way. This volume combines reliable RNAi protocols for a variety of species with discussion of strategies for the effective design of experiments using this important new technique that is changing the way experimental science is done. |
 |
Gene Silencing: New Research by Grace W. Redberry (Editor) Gene silencing is a general term describing epigenetic processes of gene regulation. The term gene silencing is generally used to describe the 'switching off' of a gene by a mechanism other than genetic mutation. That is, a gene which would be expressed (turned on) under normal circumstances, is switched off by machinery in the cell. Genes are regulated at either the transcriptional or post-transcriptional level. Transcriptional gene silencing is the result of histone modifications, creating an environment of heterochromatin around a gene that makes it inaccessible to transcriptional machinery (RNA polymerase, transcription factors, etc.). Post-transcriptional gene silencing is the result of mRNA of a particular gene being destroyed. The destruction of the mRNA prevents translation to... |
 |
siRNA and miRNA Gene Silencing: From Bench to Bedside (Methods in Molecular Biology) by Mouldy Sioud (Editor) RNA interference has become a key method in the suppression of gene expression and the development of therapeutic agents, yet there is still the problem of delivery, stability, and the danger of off-target effects such as the silencing of unwanted genes and activation of innate immunity. In siRNA and miRNA Gene Silencing: From Bench to Bedside, expert researchers explore the most recent advances in siRNA design, expression, delivery, in vivo imaging, and methods to minimize siRNA’s unwanted effects and promote successful use in patients. As part of the highly successful Methods in Molecular Biology™ series, the chapters focus on their respective subjects with easy-to-use, up-to-date information, including several step-by-step laboratory protocols on topics such as new delivery... |
 |
Therapeutic Oligonucleotides: Transcriptional and Translational Strategies for Silencing Gene Expression (Annals of the New York Academy of Sciences) by Yoon S. Cho-Chung (Editor), Alan M. Gewirtz (Editor), Cy A. Stein (Editor) The potential for the development of therapeutic oligonucleotides into clinical medicines and their use as basic research tools are explored in this volume, which is the proceedings of the 7th NIH Symposium on Therapeutic Oligonucleotides. The focus is on antisense, RNAi, triple-helix, gene repair, DNA chips, and CpG immune modulatory oligonucleotides. Specific chapters address designing better siRNAs, splice switching oligonucleotides, selective delivery of oligonucleotides, and medicinal drugs by receptor-mediated endocytosis, development of a function overriding siRNA silencing in mammalian cells, transcription factor decoys, and modified oligonucleotide hybridization and genetic insertion. NOTE: Annals volumes are available for sale as individual books or... |
|
An introduction to RNA-mediated gene silencing.: An article from: Science Progress by Mark Geanacopoulos (Author) This digital document is an article from Science Progress, published by Thomson Gale on March 22, 2005. The length of the article is 6704 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: An introduction to RNA-mediated gene silencing. Author: Mark Geanacopoulos Publication: Science Progress (Magazine/Journal) Date: March 22, 2005 Publisher: Thomson Gale Volume: 88 Issue: 1 Page: 49(21) Distributed by Thomson... | |
 |
Plant Gene Silencing by M.A. Matzke (Editor), A.J.M. Matzke (Editor) This book is an up-to-date and comprehensive collection of reviews on various aspects of epigenetic gene silencing in plants. Research on this topic has undergone explosive growth during the past decade and has revealed novel features of gene regulation and plant defense responses that also apply to animals and fungi. Gene silencing is relevant for agricultural biotechnology because stable expression of transgenes is required for the successful commercialization of genetically engineered crops. The reviews have been written by distinguished authors who have made significant contributions to plant gene silencing research. This volume supersedes other books on gene silencing by focussing on plant systems, where many pioneering experiments have been performed, and by including the... |
 |
Gene Silencing by RNA Interference: Technology and Application by Muhammad Sohail (Editor) Gene Silencing by RNA Interference: Technology and Application provides background in the field and describes methods and protocols for gene silencing. It offers a general introduction to the subject of gene silencing and RNA interference and focuses on technical details of the various methods of producing siRNAs and other RNAi tools. The final chapters of the book detail the application of RNAi to dissect gene function in a number of biological systems, including cell-free systems, cultured cells, and whole organisms. This book is a comprehensive guide to gene silencing by RNA interference methods for beginners and experienced professionals in the field. |
|
Silencing genes could prove to be golden.(genetic manipulation in control of crown-gall disease)(Brief Article): An article from: On The Plate by Consumer Alert (Publisher) This digital document is an article from On The Plate, published by Consumer Alert on October 27, 2001. The length of the article is 347 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Silencing genes could prove to be golden.(genetic manipulation in control of crown-gall disease)(Brief Article) Publication: On The Plate (Newsletter) Date: October 27, 2001 Publisher: Consumer Alert Page: NA Article Type: Brief Article Distributed by Thomson... | |
|
Proceedings of the National Academy of Sciences of the United States of America November 10, 1998, Volume 95/ Number 23: Plant Gene Silencing Regularized; Bone Homeostasis by NAS (Author) | |
|
Proceedings of the National Academy of Sciences of the United States of America July 21, 1998: Evidence for Gene Silencing; the Proton Collecting Function of the Inner Surface of Cytochrome C by NAS (Author) |
| © 2009 BrightSurf.com |