Featured Research

from universities, journals, and other organizations

Redesigned protein opens door for safer gene therapy‬

Date:
November 13, 2013
Source:
KU Leuven
Summary:
A fusion protein combining proteins active in HIV and Moloney murine leukaemia virus (MLV) replication may lead to safer, more effective retroviral gene therapy.

A fusion protein engineered by researchers at KU Leuven combining proteins active in HIV and Moloney murine leukemia virus (MLV) replication may lead to safer, more effective retroviral gene therapy.

Gene therapy involves inserting healthy genetic material into a diseased cell. Using a carrier derived from a retrovirus, the genetic material is smuggled into a human cell where, once inside, it integrates itself into the cell's DNA. But gene therapy is not without risks. If integrated too near a carcinogenic gene, the newly introduced genetic material can also induce disease-causing mutations.

In gene therapy, the delivery vehicle is not the retrovirus itself, but a viral vector: a derivative form of the retrovirus that retains its proteins but not its DNA. One of the most widely used viral vectors is derived from MLV. But this particular virus-borne carrier is both a weapon and a risk. It can cure disease but, if inscribed in the wrong place in a cell's DNA, it can also cause leukemia.

A separate protein, which plays a role in HIV, does not have that problem. It only integrates itself in 'safe' places in the host cell's DNA.

The researchers put one and two together to create a safer viral vector: "We developed a fused protein with the head of the protein that HIV uses and the tail of the protein that MLV uses," Dr. Rik Gijsbers explains.

Writing in Cell Reports, the researchers say their retrofitted retroviral vector works: "Our experiments with cell cultures show that in the presence of this protein, the viral vector always inscribes itself in a safe place, just as it does in the HIV virus," says Dr. Gijsbers.

Several years ago, scientists successfully used viral vectors derived from MLV to treat a congenital immune system abnormality in children. Some of these children later developed leukemia. "In these cases, the viral vector embedded itself near a carcinogenic gene," explains Professor Zeger Debyser, the corresponding author. "This disrupts the gene and leads to a higher leukemia risk -- a serious setback for gene therapy. It put a heavy damper on gene therapy's future development."

Until recently, it was not known how or why retroviruses inscribed themselves near cancer genes. Research by the Molecular Virology and Gene Therapy research group at KU Leuven sheds new light on this enigma. Their previous research into HIV proved essential, says Dr. Jan De Rijck: "In 2003, we discovered that HIV uses a particular protein as an anchor to embed itself into the host cell. We asked ourselves whether MLV used a different protein in a similar way, and that was indeed the case. The BET (bromodomain and extraterminal, eds.) proteins we found are the anchors of MLV." This discovery led the KU Leuven researchers to develop the fusion protein.

Though the initial results are promising, more research is needed to refine them, says Dr. Gijsbers. "But this definitely opens new avenues in the search for a new generation of safe viral vectors in gene therapy, particularly for various blood diseases."


Story Source:

The above story is based on materials provided by KU Leuven. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jan DeRijck, Christine deKogel, Jonas Demeulemeester, Sofie Vets, Sara ElAshkar, Nirav Malani, FredericD. Bushman, Bart Landuyt, StevenJ. Husson, Katrien Busschots, Rik Gijsbers, Zeger Debyser. The BET Family of Proteins Targets Moloney Murine Leukemia Virus Integration near Transcription Start Sites. Cell Reports, 2013; DOI: 10.1016/j.celrep.2013.09.040

Cite This Page:

KU Leuven. "Redesigned protein opens door for safer gene therapy‬." ScienceDaily. ScienceDaily, 13 November 2013. <www.sciencedaily.com/releases/2013/11/131113080222.htm>.
KU Leuven. (2013, November 13). Redesigned protein opens door for safer gene therapy‬. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2013/11/131113080222.htm
KU Leuven. "Redesigned protein opens door for safer gene therapy‬." ScienceDaily. www.sciencedaily.com/releases/2013/11/131113080222.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
Powered by NewsLook.com
American Ebola Patient Apparently Improving, Outbreak Is Not

American Ebola Patient Apparently Improving, Outbreak Is Not

Newsy (Aug. 19, 2014) Nancy Writebol, an American missionary who contracted Ebola, is apparently getting better, according to her husband. The outbreak, however, is not. Video provided by Newsy
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:
from the past week

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