Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers engineer virus that blocks common genetic defect


Scientists for the first time have engineered a harmless virus to correct, rather than replace, the genetic defect causing the most common single gene disorder.

The new research presents a novel approach to gene therapy in treating the most common inherited anemias: the thalassemias. Thalassemias are genetic blood diseases that result in failure to produce sufficient hemoglobin, the oxygen-carrying protein component of blood cells. This failure is caused by defects in the genetic code responsible for the production of this protein.

Scientists have explored gene therapy for these disorders for more than 20 years; only recently has this area seen a glimmer of hope. The report from the University of North Carolina at Chapel Hill is slated to appear in the Dec. 15 issue of Blood, the journal of the American Society of Hematology, and is currently online at

"This research offers a new way to treat the thalassemias, by blocking a deleterious process that causes several forms of the disease," said senior study author Dr. Ryszard Kole, professor of pharmacology, and a member of UNC Lineberger Comprehensive Cancer Center and the curriculum in genetics and molecular biology at the UNC School of Medicine.

The thalassemias are caused by a variety of different mutations in the globin gene, many of which adversely affect a process known as RNA splicing.

Three billion bases - molecules that constitute DNA - form the human genome. Only a small percentage actually code for the gene products necessary for existence. These small coding regions are like words that make sense in a long continuous string of gibberish, which must be spliced out to create a meaningful message that can then be read to make the corresponding protein. Short sequences at the border between the sense and nonsense regions, called splice sites, tell the splicing machinery where to cut, where to paste and what information can be disregarded.

Some mutations can affect splicing by creating additional splice sites in places where they should not occur. Even though the correct splice sites are still intact, the splicing machinery preferentially recognizes the incorrect splice sites, resulting in the inclusion of extra, noncoding sequences, which interfere with subsequent production of hemoglobin. Kole and colleagues found that using molecules designed to bind specific regions of RNA to block aberrant splice sites could prevent splicing machinery from using those sites.

With the aberrant sites blocked, the splicing machinery goes back to the original, correct splice sites and uses these to cut and paste the correct globin message.

"In our approach the defect in the RNA is ’masked,’ thereby effectively ’repaired.’ This is different from replacing the gene with a good copy, which will then produce additional RNA and hemoglobin," Kole said. "Since we only repair the existing RNA, we do not need to worry that too much of the good thing will be made. This can sometimes be harmful."

In collaboration with Dr. Tal Kafri, co-senior author of the study, assistant professor of microbiology and immunology and a member of the Gene Therapy Center, the antisense sequences were incorporated into a lentiviral vector.

"Lentiviral vectors appear to be the most attractive vehicles to carry therapeutic genes into non-dividing target cells such as the hematopoietic stem cells," Kafri said. "Gene delivery into these cells allows us to reconstitute a patient’s bone marrow with vector-corrected stem cells that confer a lifelong remedy. The use of antisense technology coupled with these lentiviral vectors allows us to propel this field forward in the treatment of hematopoietic disorders."

In the UNC study, the genetically modified lentiviral vector was used to treat blood cells obtained from a thalassemic patient. The treatment partially restored correct splicing in the cells and resulted in a marked increase in correct hemoglobin protein. "The results are very encouraging because even hemoglobin levels that reach less than 50 percent of normal can have a therapeutically relevant effect," said Kole.

The antisense technology explored in this study is not limited to thalassemia. The finding that the human genome comprises far fewer genes than previously thought suggests that the complexity of human beings must arise from mechanisms of gene regulation, such as splicing. According to current estimates, at least 60 percent of the human genes may be alternatively spliced.

"We have been successful in the laboratory in shifting the aberrant splicing of a few other genes involved in genetic disorders and cancer," said Kole. "With the discovery that thousands of genes are spliced, as far as potential targets for this new form of gene therapy are concerned, the sky’s the limit."

Along with Kole and Kafri, UNC co-authors include Marla M. Vacek, first author of the study and a doctoral student in the curriculum in genetics and molecular biology, and Hong Ma, a researcher in the Gene Therapy Center.

Leslie Lang | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>