Navigation Links
No danger of cancer through gene therapy virus

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
Helmholtz Association of German Research Centres

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:
(Date:11/18/2015)... , Nov. 18, 2015  As new scientific discoveries ... doctors and other healthcare providers face challenges in better ... and patients. In addition, as more children continue to ... patient,s adulthood and old age. John M. ... Children,s Hospital of Philadelphia (CHOP) . --> ...
(Date:11/17/2015)... , Nov. 17, 2015  Vigilant Solutions announces today ... its Board of Directors. --> ... recently retiring from the partnership at TPG Capital, one ... with over $140 Billion in revenue.  He founded and ... all the TPG companies, from 1997 to 2013.  In ...
(Date:11/12/2015)... , Nov. 12, 2015  Arxspan has entered ... MIT and Harvard for use of its ArxLab ... management tools. The partnership will support the institute,s ... and chemical research information internally and with external ... used for managing the Institute,s electronic laboratory notebook, ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... 25, 2015 Orexigen® Therapeutics, Inc. (Nasdaq: ... a fireside chat discussion at the Piper Jaffray 27th ... . The discussion is scheduled for Wednesday, December 2, ... .  A replay will be available for 14 days ... , Julie NormartVP, Corporate Communications and Business Development , ...
(Date:11/24/2015)... LUMPUR, Malaysia , Nov. 24, 2015 /PRNewswire/ ... global contract research organisation (CRO) market. The trend ... result in lower margins but higher volume share ... increased capacity and scale, however, margins in the ... Research Organisation (CRO) Market ( ), ...
(Date:11/24/2015)... -- Halozyme Therapeutics, Inc. (NASDAQ: HALO ) will be presenting ... on Wednesday, December 2 at 9:30 a.m. ET/6:30 a.m. ... will provide a corporate overview. th Annual Oppenheimer ... p.m. ET/10:00 a.m. PT . Jim Mazzola , vice ... overview. --> th Annual Oppenheimer Healthcare Conference in ...
(Date:11/24/2015)... ... November 24, 2015 , ... International Society for ... of the premier annual events for pharmaceutical manufacturing: 2015 Annual Meeting. The conference ... ISPE hosted the largest number of attendees in more than a decade. ...
Breaking Biology Technology: