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:4/5/2017)... 2017 KEY FINDINGS The global ... a CAGR of 25.76% during the forecast period of ... factor for the growth of the stem cell market. ... MARKET INSIGHTS The global stem cell market is ... geography. The stem cell market of the product is ...
(Date:4/3/2017)...  Data captured by IsoCode, IsoPlexis Corporation,s ... statistically significant association between the potency of ... objective response of cancer patients post-treatment. The ... cancer patients will respond to CAR-T cell ... to improve both pre-infusion potency testing and cell ...
(Date:3/30/2017)... 30, 2017 The research team of The ... (3D) fingerprint identification by adopting ground breaking 3D fingerprint minutiae recovery ... of speed and accuracy for use in identification, crime investigation, immigration ... ... A research team ...
Breaking Biology News(10 mins):
(Date:10/9/2017)... ... October 09, 2017 , ... ... in the medical journal, Epilepsia, Brain Sentinel’s SPEAC® System which uses the ... in detecting generalized tonic-clonic seizures (GTCS) using surface electromyography (sEMG). The prospective ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... its ProxiMeta™ Hi-C metagenome deconvolution product, featuring the first commercially available Hi-C ... software to perform Hi-C metagenome deconvolution using their own facilities, supplementing the ...
(Date:10/6/2017)... , ... October 06, 2017 , ... ... within the healthcare and technology sector at their fourth annual Conference where founders, ... 30 inspiring speakers and the ELEVATE pitch competition showcasing early stage digital health ...
(Date:10/5/2017)... ... October 05, 2017 , ... LabRoots , the ... from around the world, is giving back to cancer research with a month-long promotion ... , Now through October 31, shoppers can use promo code PinkRibbon to get 10 ...
Breaking Biology Technology: