Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

For Stanford Scientists, RNAi Gene Therapy Takes two Steps Forward, one Step Back

Published: Thursday, May 25, 2006
Last Updated: Thursday, May 25, 2006
Bookmark and Share
If RNAi is going to be viable as a therapy for organ-wide diseases such as hepatitis B or C, it will have to stick around.

Three years ago Mark Kay, MD, PhD, published the first results showing that a hot new biological phenomenon called RNA interference was an effective gene-therapy technique in mice.

That finding kicked off an RNAi gene therapy research flurry amongst both academic and industry research groups.

Now, with three human RNAi gene therapy trials under way, Kay's initial excitement is proving to be on target.

In the latest twist, Kay, professor of genetics and of pediatrics at the Stanford University School of Medicine, and postdoctoral fellow Dirk Grimm, PhD, report an unexpected side effect of another type of RNAi gene therapy not on trial - mice in that study suffered liver toxicity from the treatment and some died.

Despite that initial result, to be published in the May 25 issue of Nature, Kay and Grimm went on to find a way that shows promise in resolving this side effect.

"Just like any other new drug, it is just going to mean that we need to proceed cautiously," Kay said.

In traditional gene therapy the inserted DNA produces a gene to replace one that carries a mutation.

In hemophilia, for example, the inserted gene makes a protein that is missing in the blood of people with the disease.

RNAi gene therapy has the opposite effect. The inserted DNA produces a molecule called an shRNA, which turns off an overactive gene.

With key genes shut off, viruses such as hepatitis B, hepatitis C or HIV are unable to multiply and cause disease.

However, some reports had suggested that RNAi gene therapy might induce an immune reaction or switch off the wrong gene or genes.

As these concerns faded, things began looking up for RNAi with three RNAi therapies now in human trials - two for macular degeneration and one for a type of pneumonia.

However, these studies involve simply infusing the RNAi molecules into the eye or lung. The RNAi effects in these therapies aren't permanent. Instead, patients may need to receive repeat doses of the RNAi.

If RNAi is going to be viable as a therapy for organ-wide diseases such as hepatitis B or C, it will have to stick around.

Kay and Grimm felt they needed to show that the shRNA molecule made by the therapeutic gene would continue to be safe if it existed in high levels in a tissue over long periods of time.

Instead of proving the safety of RNAi gene therapy, the pair found that persistent, high levels of the shRNA made the mice sick, and in some cases the mice even died.

The problem, it seems, is that in the process of shutting down the viral genes, therapeutic shRNA molecules also hijack the cell's normal RNAi machinery.

With that machinery otherwise engaged, it's not available to carry out its normal role in the cell.

"One benefit of RNAi gene therapy is that it uses the body's own machinery, making it an effective approach," Kay said. "However, the detriment of RNAi gene therapy turns out to be that it uses the body's own machinery."

Nonetheless, Grimm and Kay bypassed the toxic effects by producing the therapeutic shRNA molecule at lower levels.

They were able to prevent the human hepatitis B virus from replicating in mouse liver for more than half a year after a single therapy using this technique.

Kay and Grimm said they have more work to do to learn the best way of making shRNA at levels high enough to be effective as gene therapy but low enough to avoid toxicity in humans.

Kay said that cancer and viral diseases such as AIDS or hepatitis B and C are likely targets for future RNAi therapies.

In order to get to these trials, Kay said he and Grimm would need to work out what caused the toxic effects in mice and further develop strategies for circumventing that reaction.

He expects that trials already under way will help him and others figure out the best way to bring RNAi gene therapy safely to humans.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,400+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Imaging Method Reveals Nanoscale Details about DNA
Enhancement to super-resolution microscopy shows orientation of individual molecules, providing a new window into DNA’s structure and dynamics.
Monday, June 20, 2016
Ultra-Sensitive Test for Cancers, HIV
Test developed that is thousands of times more sensitive than current diagnostics.
Tuesday, March 15, 2016
Marker Identifies Most Basic Form of Blood Stem Cell
Nearly 30 years after the discovery of the hematopoietic stem cell, Stanford researchers have found a marker that allows them to study the version of these stem cells that continues to replicate.
Wednesday, February 17, 2016
Flexible Gene Expression May Regulate Social Status
Scientists show how the selective expression of genes through epigenetics can regulate the social status of African cichlid fish.
Monday, January 11, 2016
Viral Infections Leave a Signature on the Immune System
A test that queries the body’s own cells can distinguish a viral infection from a bacterial infection and could help doctors know when to use antibiotics.
Thursday, December 17, 2015
Novel Approach to Understanding Brain Function
Russell Poldrack scanned his brain to create the most detailed map of brain connectivity ever.
Monday, December 14, 2015
Gene Linked to Heart Failure
Researchers have identified a previously unknown association between heart function and the narcolepsy-linked orexin receptor pathway, a finding that could provide a promising direction for treatment research.
Wednesday, December 02, 2015
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Thursday, November 26, 2015
Ancient Viral Molecules Essential for Human Development
Genetic material from ancient viral infections is critical to human development, according to researchers at the Stanford University School of Medicine.
Wednesday, November 25, 2015
Key Mechanism in Gene Expression Discovered
RNA polymerase II makes life possible by expressing genes. Now, a team of Stanford biologists, chemists and applied physicists has observed it at work in real time.
Thursday, September 17, 2015
Scientists Home In On Origin Of Human, Chimpanzee Facial Differences
A study of species-specific regulation of gene expression in chimps and humans has identified regions important in human facial development and variation.
Monday, September 14, 2015
Researchers Develop qPCR Prognosis Test for NSCLC Patients
A nine-gene molecular prognostic index (MPI) for patients with early-stage non-small cell lung cancer (NSCLC) was able to provide accurate survival stratification and could potentially inform the use of adjuvant therapy in patients struggling with the disease.
Thursday, August 20, 2015
Identifying Defective Heart Genes
A new technique could eventually enable doctors to diagnose genetic heart diseases by rapidly scanning more than 85 genes known to cause cardiac anomalies.
Thursday, August 13, 2015
Women’s Immune System Genes Operate Differently from Men’s
A new technology reveals that immune system genes switch on and off differently in women and men, and the source of that variation is not primarily in the DNA.
Friday, July 31, 2015
Scientists Discern Signatures of Old Versus Young Stem Cells
A chemical code scrawled on histones determines which genes in that cell are turned on and which are turned off.
Wednesday, July 03, 2013
Scientific News
New Possibilities Tumor Research
Grazer researchers say gene activity of the tumor from the analysis of circulating DNA in blood ahead.
Breast Cancer Cells Found To Switch Molecular Characteristics
Spontaneous interconversion between HER2-positive and HER2-negative states could contribute to progression, treatment resistance in breast cancer.
Some Breast Cancer Patients With Low Genetic Risk Could Skip Chemotherapy
Genetic test can help predict survival and guide treatment options.
LncRNAs Maintain Immune Health
Long non-coding RNAs are key controllers for maintaining immune health when fighting infection or preventing inflammatory disorders.
Enzyme that Triggers Cell Demise in ALS Identified
Scientists from Harvard have identified a key instigator of nerve cell damage in people with amyotrophic lateral sclerosis (ALS).
Molecular Alarm Clock Wakes Resting Ovules
Study of fruit flies yields discovery of a molecular "alarm clock" that activates resting ovules.
Improved Immunity in Older Age
A study from Oxford and Basel universities may point the way to maintaining our immune systems as we get older.
Neurodvelopmental Disorder Cause Linked to SON Gene
A genetic link has been discovered for a previously unxplained neurodevelopmental disorder.
Russian TB Thrives Within Macrophages
MIPT researchers have identified features of mycobacterium tuberculosis strains that may explain their success.
Gene Linked to Hearing Loss Identified
Researchers have identifed a gene associated with age-related hearing loss.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!