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:5/20/2016)... -- VoiceIt is excited to announce its new marketing ... working together, VoiceIt and VoicePass will offer an ... slightly different approaches to voice biometrics, collaboration between ... Both companies ... "This marketing and technology partnership allows VoiceIt ...
(Date:5/12/2016)... 12, 2016 WearablesResearch.com , a brand ... overview results from the Q1 wave of its quarterly ... was consumers, receptivity to a program where they would ... health insurance company. "We were surprised to ... Michael LaColla , CEO of Troubadour Research, "primarily ...
(Date:5/3/2016)...  Neurotechnology, a provider of high-precision biometric identification ... Identification System (ABIS) , a complete system for ... can process multiple complex biometric transactions with high ... face or iris biometrics. It leverages the core ... MegaMatcher Accelerator , which have been used in ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016 A person commits a crime, and ... to track the criminal down. An outbreak of ... Drug Administration (FDA) uses DNA evidence to track down the ... Sound far-fetched? It,s not. The FDA has increasingly used a ... of foodborne illnesses. Put as simply as possible, whole genome ...
(Date:6/23/2016)... June 23, 2016   EpiBiome , a precision ... million in debt financing from Silicon Valley Bank (SVB). ... and to advance its drug development efforts, as well ... "SVB has been an incredible strategic partner ... a traditional bank would provide," said Dr. Aeron ...
(Date:6/23/2016)... June 23, 2016  Blueprint Bio, a company dedicated ... the medical community, has closed its Series A funding ... . "We have received a commitment from ... we need to meet our current goals," stated ... the runway to complete validation on the current projects ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity Products, ... tools designed, tuned and optimized exclusively for Okuma CNC machining centers at The ... of a collaboration among several companies with expertise in toolholding, cutting tools, machining ...
Breaking Biology Technology: