A newly designed viral vector the vehicle that delivers a gene therapyto a patients cells for use insickle cell anemia is more efficient than earlier vectors at introducing healthy copies of genes into stem cells and can be produced in greater amounts, studies in animal models show.
The study Development of a forward-orientated therapeutic lentiviral vector for hemoglobin disorders was published in the journal Nature Communications.
Hemoglobin is the protein in red blood cells that binds oxygen, allowing oxygen to be transported around the body. Mutations in the HBBgene, which encodes a component of hemoglobin, causessickle cell.
Gene therapies involve either altering the mutated gene or introducing a healthy version of that gene to the body. Still under development for sickle cell, an estimated 27 patients have undergone experimental gene therapy. One strategy involves removing hematopoietic stem cells (which function to produce blood cells) from a patients bone marrow. A healthy copy of the HBB gene is then introduced into the cells using a modified, harmless virus known as a viral vector. The cells are then transplanted back into the patient where they will produce healthy red blood cells.
Traditionally, viral vectors for sickle cell have been designed in a way known as reverse structural orientation. This means that the HBB gene is translated or read from right to left, like reading an English sentence backwards. The reverse structural orientation design ensures that a key section of the gene (known as intron 2), which is necessary for the production of high levels of the HBB gene, is retained during viral vector preparation.
However, this design makes preparing the viral vectors more difficult, and decreases the efficiency of introducing the gene into the stem cells.
Researchersat the National Institutes of Healthdesigned a new viral vector, one in which the HBB gene is forward orientated and read from left to right. Genes essential for the virus were inserted into intron 2, meaning that only vectors that retained intron 2 would be produced (a type of positive selection).
Our new vector is an important breakthrough in the field of gene therapy for sickle cell disease, John Tisdale, MD, chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute (NHLBI) and the studys senior author, said in a press release.
Its the new kid on the block and represents a substantial improvement in our ability to produce high capacity, high efficiency vectors for treating this devastating disorder, he added.
The researchers compared the new vectors to traditional reverse-orientated vectors in mouse and monkey models. The new vectors were four to 10 times more efficient at introducing the healthy HBBgene into the stem cells, and could carry up to six times more HBB genes compared to the conventional vectors.
Furthermore, the new vectors remained incorporated into the cells of monkeys up to four years after a transplant. These vectors could also be produced in greater amounts, which may lessen the time and costs required for large-scale vector production.
The researchers hope that these characteristics will make gene therapy for sickle cell disease more effective and increase its use. The new vector design still needs to be tested in clinical trials in patients.
Our lab has been working on improving beta-globin vectors for almost a decade and finally decided to try something radically different and it worked, Tisdale said.
These findings bring us closer to a curative gene therapy approach for hemoglobin disorders, he added.
Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
Total Posts: 94
Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
Here is the original post:
New Viral Vector for Sickle Cell Gene Therapy Likely to Be More Effective, NIH Study Says - Sickle Cell Anemia News
- Politics of Stem Cell Research - May 7th, 2011 [May 7th, 2011]
- Obama Ends Funding Ban for Stem Cell Research - May 8th, 2011 [May 8th, 2011]
- Stem Cell Research: A Father's Fight - May 10th, 2011 [May 10th, 2011]
- Human Embryonic stem cell research - May 11th, 2011 [May 11th, 2011]
- Frost Over The World - Stem Cell Research and Turkey -26 Oct - May 20th, 2011 [May 20th, 2011]
- McCain Favors Embryonic Stem Cell Research - May 20th, 2011 [May 20th, 2011]
- US divided over stem cell research reversal - 09 Mar 09 - May 21st, 2011 [May 21st, 2011]
- The Politics and Promise of Stem Cell Research - May 22nd, 2011 [May 22nd, 2011]
- Inside Story - Obama to end stem cell research ban - March 9 - Part1 - May 30th, 2011 [May 30th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Douglas Boyd - June 3rd, 2011 [June 3rd, 2011]
- The Human Embryo and Embryonic Stem Cell Biology: Spotlight on Stem Cell Research - June 3rd, 2011 [June 3rd, 2011]
- US appeals court lifts stem cell research ban - June 7th, 2011 [June 7th, 2011]
- Trailer for Mapping Stem Cell Research: Terra Incognita - June 9th, 2011 [June 9th, 2011]
- Politics: President Obama on Stem Cell Research - June 10th, 2011 [June 10th, 2011]
- Stem Cell Research Documentary - June 11th, 2011 [June 11th, 2011]
- TEDxSingapore - Susan Lim - Hype and hope of stem cell research - June 13th, 2011 [June 13th, 2011]
- Lou Gehrig's Disease (ALS): Spotlight on Stem Cell Research - Wrapup - June 14th, 2011 [June 14th, 2011]
- The Next Frontier in Stem Cell Research - June 17th, 2011 [June 17th, 2011]
- Robert Klein: Stem Cell Research - June 22nd, 2011 [June 22nd, 2011]
- Fibrocell Stem-Cell Wrinkle Smoother Wins FDA Clearance - June 23rd, 2011 [June 23rd, 2011]
- The Politics of Stem Cell Research - June 23rd, 2011 [June 23rd, 2011]
- A Dose of Reality on Alternative Stem Cell Treatments: What you don't know can hurt you - June 28th, 2011 [June 28th, 2011]
- Governor Tim Pawlenty Discusses Stem Cell Research - June 30th, 2011 [June 30th, 2011]
- The EU and stem cell research - July 5th, 2011 [July 5th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Jeff Bronstein - July 6th, 2011 [July 6th, 2011]
- Cardiovascular Therapies: Spotlight on Stem Cell Research - Yung-Wei Chi - July 7th, 2011 [July 7th, 2011]
- Spotlight on Cancer Stem Cell Research - July 11th, 2011 [July 11th, 2011]
- A Stem Cell Story - July 12th, 2011 [July 12th, 2011]
- Bishop Blair bars support for Komen breast cancer group - July 13th, 2011 [July 13th, 2011]
- Stem Cell Research In Toronto - July 14th, 2011 [July 14th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Introduction - July 14th, 2011 [July 14th, 2011]
- Huntington's Disease: Spotlight on Stem Cell Research 2007 - Han Keirstead - July 15th, 2011 [July 15th, 2011]
- TMconfUK2011-08 - Stem Cell Research in the UK - Prof Charles Ffrench-Constant - July 16th, 2011 [July 16th, 2011]
- UCSF opens stem cell research building - July 16th, 2011 [July 16th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - John Zaia - July 17th, 2011 [July 17th, 2011]
- Deafness: Spotlight on Stem Cell Research - Ebenezer Yamoah - July 22nd, 2011 [July 22nd, 2011]
- Spotlight on Basic Stem Cell Research - Irv Weissman - July 25th, 2011 [July 25th, 2011]
- Diabetes: Spotlight on Stem Cell Research - Peter Butler - July 27th, 2011 [July 27th, 2011]
- Parkinson's Disease: Spotlight on Stem Cell Research - Arnold Kriegstein - July 27th, 2011 [July 27th, 2011]
- HIV/AIDS: Spotlight on Stem Cell Research - Loren Leeds - July 27th, 2011 [July 27th, 2011]
- Alzheimer's Disease: Spotlight on Stem Cell Research - Leeza Gibbons - August 2nd, 2011 [August 2nd, 2011]
- Geron's Embryonic Stem Cell Clinical Trial for Spinal Cord Injury - August 3rd, 2011 [August 3rd, 2011]
- The Skin Gun stem cell research - August 10th, 2011 [August 10th, 2011]
- Deafness: Spotlight on Stem Cell Research - Karen Doyle - August 10th, 2011 [August 10th, 2011]
- Stem Cell Research: Huntington's Disease - August 14th, 2011 [August 14th, 2011]
- Adult and Non-Embryonic Stem Cell Research Conference at Notre Dame - August 20th, 2011 [August 20th, 2011]
- Stemcell Research and Aging - Panel 1 - August 22nd, 2011 [August 22nd, 2011]
- Texans for Stem Cell Research Learn for Life: KXAN Coverage Aired August 16th, 2011 - August 24th, 2011 [August 24th, 2011]
- Stem Cell Research: Macular Degeneration - September 18th, 2011 [September 18th, 2011]
- Brilliant Minds - Stem Cell Research | Tomorrow Today - September 25th, 2011 [September 25th, 2011]
- Ethics of Stem Cell Research (1) - September 29th, 2011 [September 29th, 2011]
- Legal and Public Policy Dimensions of Stem Cell Research - September 29th, 2011 [September 29th, 2011]
- Stem cell symposium - October 2nd, 2011 [October 2nd, 2011]
- StemCONN 2011, The Latest in Stem Cell Research - October 6th, 2011 [October 6th, 2011]
- Arthritis: Spotlight on Stem Cell Research - Mark Genovese - October 7th, 2011 [October 7th, 2011]
- Judy Roberson: Patient advocates drive stem cell scientists - October 8th, 2011 [October 8th, 2011]
- Sam Harris - Stem Cells and Morality - October 8th, 2011 [October 8th, 2011]
- Stem Cell Research, Ethics and Religion - October 9th, 2011 [October 9th, 2011]
- Stem Cells: Fulfilling the Promise - 2011 CIRM Grantee Meeting - October 10th, 2011 [October 10th, 2011]
- The Skin Gun (Stem Cell research to replace burnt off skin. Done in 3 days!) - October 13th, 2011 [October 13th, 2011]
- Alzheimer's Stem Cell Research Patient Advocate Spotlight: The Faces of Neurodegenerative Disease - Video - October 18th, 2011 [October 18th, 2011]
- Life in the Balance: Perspectives on Stem Cell Research - Video - October 18th, 2011 [October 18th, 2011]
- Stem Cell Research Funding Halt - Video - October 19th, 2011 [October 19th, 2011]
- Vatican lending hand in adult stem cell research - Video - October 20th, 2011 [October 20th, 2011]
- First Spinal-Cord Surgery With Stem Cells - Video - October 21st, 2011 [October 21st, 2011]
- Michael J. Fox Embryonic Stem Cell Research - Video - October 22nd, 2011 [October 22nd, 2011]
- stem cell research - Video - October 22nd, 2011 [October 22nd, 2011]
- Gayle Atteberry - Cloning - November 5th, 2011 [November 5th, 2011]
- It Takes Nerve: UC Irvine - Sue - November 6th, 2011 [November 6th, 2011]
- Embryonic Stem Cell Research - Video - November 9th, 2011 [November 9th, 2011]
- Adult Stem Cell Research Far Ahead of Embryonic - Video - November 10th, 2011 [November 10th, 2011]
- Is stem cell research a growing concern .flv - Video - November 10th, 2011 [November 10th, 2011]
- Forbes Discusses Stem Cell Research - Video - November 14th, 2011 [November 14th, 2011]
- Stem Cell Research Presentation - Video - November 16th, 2011 [November 16th, 2011]
- Benedict XVI: No embryonic stem cell research - Video - November 28th, 2011 [November 28th, 2011]
- Batten Disease: Spotlight on Stem Cell Research - A Father's Story - Video - November 30th, 2011 [November 30th, 2011]
- CIS 111 Digital Media Project - Stem Cell Research - Video - December 13th, 2011 [December 13th, 2011]
- Regenerative Medicine and Applications of Stem Cell Research - Video - December 20th, 2011 [December 20th, 2011]
- Stem Cell Research Today: Larry Goldstein - CIRM Science Writer's Seminar - Video - December 22nd, 2011 [December 22nd, 2011]
- CIRM Bridges Award: Building California's Stem Cell Research Workforce - Video - December 22nd, 2011 [December 22nd, 2011]