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Biotech / Medical : ARIAD Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (442)	1/15/1999 6:27:00 PM
From: Mike McFarland	Read Replies (1) \| Respond to of 4474

After having a lot of problems posting over on Yahoo, I think I'll stay here, apologies to the thread and the folks over on yahoo who lurk here for having made so much noise. the post over there to read is aria #633 messages.yahoo.com@m2.yahoo.com Anyway, the most recent patent which comes up when you do a title search for aav turns up... United States Patent 5,856,152 Wilson , et al. January 5, 1999 Hybrid adenovirus-AAV vector and methods of use therefor Abstract The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5' and 3' ITR sequences from an AAV, and a selected transgene. Other hybrid vectors form a polycation conjugate and incorporate an AAV rep gene in a single particle. These hybrid virus vectors are characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. Also disclosed is the use of the hybrid vectors to produce large quantities of recombinant AAV. Inventors: Wilson; James M. (Gladwyne, PA); Kelley; William M. (Ann Arbor, MI); Fisher; Krishna J. (Philadelphia, PA) Assignee: The Trustees of the University of Pennsylvania (Philadelphia, PA) Appl. No.: 331384 Filed: October 28, 1994 Here is the SUMMARY OF THE INVENTION In one aspect, the present invention provides a unique hybrid adenovirus/AAV viral particle, which comprises an adenovirus capsid containing selected portions of an adenovirus sequence, 5' and 3' AAV ITR sequences which flank a selected transgene under the control of a selected promoter and other conventional vector regulatory components. This hybrid viral particle is characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. In one embodiment, the transgene is a reporter gene. Another embodiment of the hybrid viral particle contains a therapeutic transgene. Still another embodiment of the hybrid vector particle has associated therewith a polycation sequence. Another embodiment of the hybrid viral particle also includes an AAV rep gene. In another aspect, the present invention provides a hybrid vector construct for use in producing the viral particle described above. This hybrid vector comprises selected portions of an adenovirus sequence, 5' and 3' AAV ITR sequences which flank a selected transgene under the control of a selected promoter and other conventional vector regulatory components. Another embodiment of the hybrid viral particle also includes an AAV rep gene. In another aspect, the invention provides a method for delivering a selected gene to a host cell for expression in that cell by employing the hybrid viral particle of this invention. Such a method may be employed to deliver a therapeutic gene to a targeted host cell to treat or correct a genetically associated disorder or disease. In yet another aspect, the present invention provides a method for producing the hybrid viral particle by transfecting a suitable packaging cell line with the hybrid construct of this invention. In another embodiment the method involves co-transfecting a cell line (either a packaging cell line or a non-packaging cell line) with a hybrid construct and a suitable helper adenovirus. In a further aspect, the present invention provides a method for producing large quantities of recombinant AAV particles with high efficiency by employing the above methods, employing the hybrid construct of this invention and collecting the rAAV particles from a cell line transfected with the vector. Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof. eom