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Biotech / Medical : TGEN - Targeted Genetics Corporation -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (246)	2/7/2000 2:05:00 PM
From: Mike McFarland	Read Replies (1) \| Respond to of 557

I guess if a person was comfortable bugging investor relations, you could ask if A. Dusty Miller and TGEN are working together on AAV6, my guess is that it is likely--I am sure that they have had a close relationship in the past. I wonder how long it takes to put a specific serotype through the cooker, and what TGEN has done to engineer specific vectors-- we always here "AAV", but these Gene Therapy companies must be playing with different variations all the time. If AAV2 and AAV6 are the best, and the FHCRC has something to do with it, we should keep an eye on TGEN and see if they ever say anything about these 'serotypes'. I did a little reading last night, I see that rhinovirus has a hundred or more different types--which is why you never become immune to the common cold. Learning a little bit each day. I think I was a little too quick swapping Ariad for TGEN though, yikes, ARIA at $14 today--and a marketcap significantly higher than tgen, I always sell too early-- will try to be more patient with tgen. Repeat transduction in the mouse lung by using adeno-associated virus vectors with different serotypes. Halbert CL, Rutledge EA, Allen JM, Russell DW, Miller AD J Virol 2000 Feb;74(3):1524-32 Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. [Medline record in process] Vectors derived from adeno-associated virus type 2 (AAV2) promote gene transfer and expression in the lung; however, we have found that while gene expression can persist for at least 8 months in mice, it was reduced dramatically in rabbits over a period of 2 months. The efficiency and persistence of AAV2-mediated gene expression in the human lung have yet to be determined, but it seems likely that readministration will be necessary over the lifetime of an individual. Unfortunately, we have found that transduction by a second administration of an AAV2 vector is blocked, presumably due to neutralizing antibodies generated in response to the primary vector exposure. Here, we have explored the use of AAV2 vectors pseudotyped with capsid proteins from AAV serotypes 2, 3, and 6 for readministration in the mouse lung. We found that an AAV6 vector transduced airway epithelial and alveolar cells in the lung at rates that were at least as high as those of AAV2 pseudotype vectors, while transduction rates mediated by AAV3 were much lower. AAV6 pseudotype vector transduction was unaffected by prior administration of an AAV2 or AAV3 vector, and transduction by an AAV2 pseudotype vector was unaffected by prior AAV6 vector administration, showing that cross-reactive neutralizing antibodies against AAV2 and AAV6 are not generated in mice. Interestingly, while prior administration of an AAV2 vector completely blocked transduction by a second AAV2 pseudotype vector, prior administration of an AAV6 vector only partially inhibited transduction by a second administration of an AAV6 pseudotype vector. Analysis of sera obtained from mice and humans showed that AAV6 is less immunogenic than AAV2, which helps explain this finding. These results support the development of AAV6 vectors for lung gene therapy both alone and in combination with AAV2 vectors. PMID: 10627564, UI: 20094940