Navigation Links
Sickle cell disease corrected in human models using stem cell-based gene therapy

In a study to be published in the January 2006 issue of Nature Biotechnology, researchers led by a team of scientists at Memorial Sloan-Kettering Cancer Center have devised a novel strategy that uses stem cell-based gene therapy and RNA interference to genetically reverse sickle cell disease (SCD) in human cells. This research is the first to demonstrate a way to genetically correct this debilitating blood disease using RNA interference technology.

To prevent the production of the abnormal hemoglobin that causes sickle cell disease, a viral vector was introduced in cell cultures of patients who have the disease. The vector carried a therapeutic globin gene harboring an embedded small interfering RNA precursor designed to suppress abnormal hemoglobin formation. Tested in adult stem cells from SCD patients, researchers found that the newly formed red blood cells made normal hemoglobin and suppressed production of the sickle shaped hemoglobin typical of the disease.

"Sickle cell disease can only be cured by transplanting healthy blood-forming stem cells from another individual, but this option is not available to most patients due to the difficulty in finding a compatible donor," explained Michel Sadelain, MD, PhD, of the Immunology Program at MSKCC and the study's senior author. "By using gene transfer, there is always a donor match because the patient's own stem cells are used to treat the disease."

Sickle cell disease is a genetic condition that causes an abnormal type of hemoglobin to be made in red blood cells. The aggregation of hemoglobin S inside red cells interferes with the body's blood cells' ability to flow through small blood vessels, depriving tissues of adequate oxygen supply. This can cause pain, anemia, infections, organ damage, and stroke. Approximately 80,000 people in the United States have this inherited condition, which is primarily found in people of African, Mediterranean, Indian, or Middle Eastern origin. There is no kn own cure other than stem cell transplantation.

To treat SCD, Sloan-Kettering scientists devised a novel engineering strategy combining RNA interference with globin gene transfer by creating a therapeutic transgene, consisting of the gamma-globin gene and small interfering RNA specific for beta S-globin, the globin mutant chain that causes sickle cell disease.

"An innovative and sophisticated approach was needed to genetically engineer hematopoietic stem cells using a practical and clinically applicable process. The transferred gene must not disrupt the cells' normal functions," explained Isabelle Riviere, PhD, Co-Director of the Gene Transfer and Somatic Cell Engineering Facility and a study co-author.

The new gene had two functions -- produce normal hemoglobin and suppress the generation of sickle shaped hemoglobin S. The therapeutic gene was engineered into a lentiviral vector and introduced into hematopoietic stem cells. After the cells received the treatment, they made normal hemoglobin.

"This proved our hypothesis that you can simultaneously add one function and delete another in the same cell and obtain synergistic genetic modifications within a single cell," said Selda Samakoglu, PhD, a member of Dr. Sadelain's laboratory and the study's first author. "In this case, we used the technique to correct sickle cell disease, but it should be broadly applicable to use therapeutically in stem cells or malignant cells."


'"/>

Source:Memorial Sloan-Kettering Cancer Center


Related biology news :

1. Discovery Promises Simpler Therapy for Sickle Cell Disease
2. Sickle cell and protection against malaria
3. Neuronal traffic jam marks early Alzheimers disease
4. Scientists detect probable genetic cause of some Parkinsons disease cases
5. Ecological destruction fuels emerging diseases
6. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
7. U of M researcher examines newly emerging deadly disease
8. Marburg virus disease in Angola - update
9. Molecular machine may lead to new drugs to combat human diseases
10. Female sex hormones play a vital role in defense against sexually transmitted diseases
11. A bacterial genome reveals new targets to combat infectious disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/11/2016)... , March 11, 2016 ... new market research report "Image Recognition Market by Technology ... (Marketing and Advertising), by Deployment Type (On-Premises and Cloud), ... To 2022", published by MarketsandMarkets, the global market is ... to USD 29.98 Billion by 2020, at a CAGR ...
(Date:3/9/2016)... , March 9, 2016  Crossmatch ® ... and enrollment solutions, today announced the addition of ... Altus multi-factor authentication platform. New contextual ... managers to step-up security where it,s needed most ... Washington, DC . --> ...
(Date:3/2/2016)... March 2, 2016 ... addition of the  "Global Biometrics Market in ... ,     (Logo: http://photos.prnewswire.com/prnh/20130307/600769) , , Global biometrics ... at a CAGR of around 27%   ... has announced the addition of the  "Global ...
Breaking Biology News(10 mins):
(Date:5/3/2016)... ... May 03, 2016 , ... Morf Media Inc ... training platform on mobile devices, today released a new interactive Food and ... Devices. The course is essential for owners or operators of places of business ...
(Date:5/3/2016)... ... 03, 2016 , ... Leading CEOs from biotech, pharmaceutical, and ... June 1st at The Four Seasons Hotel Boston. , The Boston CEO Conference ... exclusive access to key decision makers who influence deal making and investment. Attendees ...
(Date:5/3/2016)... MA (PRWEB) , ... May 03, 2016 , ... ... that facilitates accessibility to unique bioresearch materials from laboratories across the globe, today ... researchers scramble to increase the pace of research toward treatment and prevention measures ...
(Date:5/3/2016)... 3, 2016 - And Other ... Producers of Those Competitor Biologics  - Biosimilar ... and Prospects ,  Who are the most ... what are their sales potentials? Discover, in our updated ... trends, opportunities and revenue forecasting. Visiongain,s ...
Breaking Biology Technology: