Navigation Links
No danger of cancer through gene therapy virus
Date:6/19/2013

In fall 2012, the European Medicines Agency (EMA) approved the modified adeno-associated virus AAV-LPL S447X as the first ever gene therapy for clinical use in the Western world. uniQure, a Dutch biotech company, had developed AAV-LPL S447X for the treatment of a rare inherited metabolic disease called lipoprotein lipase deficiency (LPLD) which affects approximately one or two out of one million people. The disease causes severe, life-threatening inflammations of the pancreas. Afflicted individuals carry a defect in the gene coding for the lipoprotein lipase enzyme which is necessary for breakdown of fatty acids. AAV-LPLS447X shall be used as a viral vector to deliver an intact gene copy to affected cells.

The viruses modified for gene therapy cannot integrate their DNA into the host cell genome, because they lack a particular enzyme needed for this. Nevertheless, integration may happen occasionally. "We had to exclude that AAV-LPLS447X tends to integrate at sites in the genome where this integration might activate cancer-promoting genes. This is exactly what had been observed with a virus used for gene therapy," says Dr. Manfred Schmidt, a molecular biologist. Schmidt leads a research group at NCT Heidelberg and DKFZ that studies the safety of gene-therapeutic methods.

In collaboration with scientists from uniQure, the Heidelberg researchers analyzed the genome of five LPLD patients who had been treated with AAV-LPLS447X . In addition, they also studied mice following intramuscular or intravenous administration of the therapeutic virus.

The analysis of 15 million individual genomes of five treated patients showed, as expected, that AAV-LPLS447X rarely integrates into the genome of the host cells (fewer than 1 out of 1,000 AAV-LPLS447X particles). In most cases, the viral genome persists in the cytoplasm as a separate structure. If it is integrated, this happens at random sites. The researchers did not find any tendency for integration at particular sites in the genome.

Christine Kaeppel and Raffaele Fronza, first authors of the article, were very surprised to discover the AAV-LPLS447X genome in the so-called mitochondrial genome. Mitochondria are tiny membrane-enclosed structures that generate energy for the cell. They are the only cellular component aside from the nucleus containing DNA. "An adeno-associated virus has never before been observed to integrate into the mitochondrial genome on its own," reported the scientists.

"For the first time, we have thoroughly analyzed in AAV-treated patients whether and where the viral genome integrates. Now we can regard AAV-LPLS447X as safe. Those few cases where we have observed integration of viral DNA in muscle cells are barely relevant in view of all the reconstructions and rearrangements that are permanently taking place in our DNA anyway," says study director Schmidt.

AAV-LPLS447X is considered to be a prototype vector for gene therapy. "If AAV-LPLS447X stands the test, other gene therapies against more common diseases such as Huntington's disease or Parkinson's might also become possible," says Schmidt. In addition, a growing number of diseases have been found to be linked to alterations in mitochondrial genes. The newly discovered property of the AAV vector might also prove useful for correcting genetic defects in human mitochondrial DNA.


'/>"/>

Contact: Dr. Sibylle Kohlstädt
s.kohlstaedt@dkfz.de
Helmholtz Association of German Research Centres
Source:Eurekalert

Related biology news :

1. Drought, river fragmentation forcing endangered fish out of water, biologist finds
2. Saving the parrots: Texas A&M team sequences genome of endangered macaw birds
3. Agencies should use common approach to evaluate risks pesticides pose to endangered species
4. MRI measure of blood flow over atherosclerotic plaque may detect dangerous plaque
5. Study documents decimation of critically endangered forest elephant
6. Genetic analysis calls for the protection of 2 highly endangered Portuguese fish species
7. Study: Widespread test-and-treat HIV policies could increase dangerous drug resistance
8. Social bees mark dangerous flowers with chemical signals
9. The natural ecosystems in the Colombian Orinoco Basin are in danger
10. Avoiding virus dangers in domesticating wild plants for biofuel use
11. DNA reveals mating patterns of critically endangered sea turtle
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/10/2016)... , March 10, 2016   Unisys Corporation ... and Border Protection (CBP) is testing its biometric identity ... San Diego to help identify certain non-U.S. citizens ... . The test, designed to help determine the efficiency and ... began in February and will run until May 2016. ...
(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:3/3/2016)... March 3, 2016  2016FLEX, organized by FlexTech, ... highlighting advancements in flexible, hybrid and printed electronics. ... attendance - have gathered for short courses, technical ... of electronics. The Flex Conference celebrates its 15 ... companies, R&D organizations, and universities contributing to the ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... April 27, 2016 , ... Cambridge Semantics, the leading ... today announced that it has been named to The Silicon Review’s “20 Fastest Growing ... other markets, Cambridge Semantics serves the needs of end users facing some of the ...
(Date:4/27/2016)... VANCOUVER, British Columbia , April 27, 2016 ... "Gesellschaft" oder "NanoStruck") (CSE: NSK) (OTCPink: NSKQB) ( ... sie im Anschluss an ihre Pressemitteilung vom 13. ... Inc. erhalten hat, ihre Finanzen um zusätzliche 200.000.000 ... auf 4.000.000 Kanadische Dollar zu bringen. Davon wurden ...
(Date:4/27/2016)... , ... April 27, 2016 , ... ... PhD to its Scientific Advisory Board. Dr. Lamka will assist PathSensors in expanding ... detection. , PathSensors deploys the CANARY® test platform for the detection of ...
(Date:4/27/2016)... 27, 2016 MedDay, a biotechnology company ... the appointment of Catherine Moukheibir as Chairman of its Board ... Jean Jacques Garaud , who contributed to the rapid ... immediately. Catherine started her career in strategy consulting ... London .  She held C-Suite level roles ...
Breaking Biology Technology: