Featured Research

from universities, journals, and other organizations

New gene therapy technique on iPS cells holds promise in treating immune system disease

Date:
April 28, 2011
Source:
American Society of Hematology
Summary:
Researchers have developed an effective technique that uses gene therapy on stem cells to correct chronic granulomatous disease in cell culture, which could eventually serve as a treatment for this rare, inherited immune disorder, according to a new study.

Researchers have developed an effective technique that uses gene therapy on stem cells to correct chronic granulomatous disease (CGD) in cell culture, which could eventually serve as a treatment for this rare, inherited immune disorder, according to a study published in Blood, the Journal of the American Society of Hematology.

CGD prevents neutrophils, a type of white blood cell of the immune system, from making hydrogen peroxide, an essential defense against life-threatening bacterial and fungal infections. Most cases of CGD are a result of a mutation on the X chromosome, a type of CGD that is called "X-linked" (X-CGD).

While antibiotics can treat infections caused by X-CGD, they do not cure the disease itself. Patients with X-CGD can be cured with a hematopoietic stem cell (HSC) transplant from healthy bone marrow; however, finding a compatible donor is difficult. Even with a suitable donor, patients are at risk of developing graft-versus-host disease (GVHD), a serious and often deadly post-transplant complication that occurs when newly transplanted donor cells recognize a recipient's own cells as foreign and attack the patient's body.

Another treatment option under development for X-CGD is gene therapy, a technique for correcting defective genes responsible for disease development that involves manipulation of genetic material within an individual's blood-forming stem cells using genetically engineered viruses. However, this gene therapy has so far proved to be inefficient at correcting X-CGD. In addition, these engineered viruses insert new genetic material at random locations in the blood-forming stem cell genome, putting patients at significantly higher risk for developing genetic mutations that may eventually lead to serious blood disorders, including blood cancer.

In order to develop a more effective and safer gene therapy for X-CGD, researchers from the National Institute of Allergy and Infectious Disease (NIAID) at the National Institutes of Health (NIH) and The Johns Hopkins University School of Medicine embarked on a study using a more precise method for performing gene therapy that did not use viruses for the gene correction. Researchers removed adult stem cells from the bone marrow of a patient with X-CGD and genetically reprogrammed them to become induced pluripotent stem cells (iPS cells). Like embryonic stem cells, these patient-specific iPS cells can be grown and manipulated indefinitely in culture while retaining their capacity to differentiate into any cell type of the body, including HSCs.

"HSCs that are derived from gene corrected iPS cells are tissue-compatible with the patient and may create a way for the patient's own cells to be used in a transplant to cure the disease, removing the risk of GVHD or the need to find a compatible donor," said Harry L. Malech, MD, senior study author, Chief of the Laboratory of Host Defenses and Head of the Genetic Immunotherapy Section of NIAID at the NIH. "However, turning iPS cells into a large number of HSCs that are efficently transplantable remains technically difficult; therefore, our study aimed at demonstrating that it is possible to differentiate gene corrected iPS cells into a large number of corrected neutrophils. These corrected neutrophils, grown in culture, are tissue-compatible with the patient and may be used to manage the life-threatening infections that are caused by the disease."

Typically, iPS cells from a patient with an inherited disorder do not express disease traits, despite the fact that the iPS cell genome contains the expected mutation. The researchers were able to prove, in culture, that iPS cells from a patient with X-CGD could be differentiated into mature neutrophils that failed to produce hydrogen peroxide, thus expressing the disease trait. This is the first study in which the disease phenotype has been reproduced in neutrophils differentiated from X-CGD patient-specific iPS cells.

After discovering that the disease could be reproduced in cell culture, the researchers then sought to correct the disease and produce healthy neutrophils in culture. They used synthetic proteins called zinc finger nucleases (ZFNs) to target a corrective gene at a specifically defined location in the genome of the X-CGD iPS cells. The iPS cells were then carefully screened to identify those containing a single copy of the corrective gene properly inserted only at the safe site. The researchers observed that some of the gene-corrected iPS cells could differentiate into neutrophils that produced normal levels of hydrogen peroxide, effectively "correcting" the disease.

"This is the first study that uses ZFNs in specific targeting gene transfer to correct X-CGD," said Dr. Malech. "Demonstrating that this approach to gene therapy works with a single-gene disease such as X-CGD means that the results from our study offer not only a potential treatment for this disease, but more importantly, a technique by which other single-gene diseases can be corrected using specifically targeted gene therapy on iPS cells."


Story Source:

The above story is based on materials provided by American Society of Hematology. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Zou, C. L. Sweeney, B.-K. Chou, U. Choi, J. Pan, H. Wang, S. N. Dowey, L. Cheng, H. L. Malech. Oxidase deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease mediated safe harbor targeting. Blood, 2011; DOI: 10.1182/blood-2010-12-328161

Cite This Page:

American Society of Hematology. "New gene therapy technique on iPS cells holds promise in treating immune system disease." ScienceDaily. ScienceDaily, 28 April 2011. <www.sciencedaily.com/releases/2011/04/110428112549.htm>.
American Society of Hematology. (2011, April 28). New gene therapy technique on iPS cells holds promise in treating immune system disease. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2011/04/110428112549.htm
American Society of Hematology. "New gene therapy technique on iPS cells holds promise in treating immune system disease." ScienceDaily. www.sciencedaily.com/releases/2011/04/110428112549.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Despite Health Questions, E-Cigs Are Beneficial: Study

Despite Health Questions, E-Cigs Are Beneficial: Study

Newsy (July 31, 2014) Citing 81 previous studies, new research out of London suggests the benefits of smoking e-cigarettes instead of regular ones outweighs the risks. Video provided by Newsy
Powered by NewsLook.com
Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
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