Featured Research

from universities, journals, and other organizations

RNA Interference Gene Therapy Takes Two Steps Forward, One Step Back

Date:
May 28, 2006
Source:
Stanford University Medical Center
Summary:
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.

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.

Related Articles


Now, with three human RNAi gene therapy trials under way, Kay's initial excitement is proving to be on target. However, reaching this point hasn't been without challenges. 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.

Postdoctoral fellows Konrad L. Streetz, PhD, and Catherine L. Jopling, PhD; research assistants Theresa A. Storm and Kusum Pandey, and veterinary pathologist Corrine R. Davis, DVM, PhD, contributed to the study.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Stanford University Medical Center. "RNA Interference Gene Therapy Takes Two Steps Forward, One Step Back." ScienceDaily. ScienceDaily, 28 May 2006. <www.sciencedaily.com/releases/2006/05/060528161548.htm>.
Stanford University Medical Center. (2006, May 28). RNA Interference Gene Therapy Takes Two Steps Forward, One Step Back. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2006/05/060528161548.htm
Stanford University Medical Center. "RNA Interference Gene Therapy Takes Two Steps Forward, One Step Back." ScienceDaily. www.sciencedaily.com/releases/2006/05/060528161548.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins