The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5â and 3â 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.
Method For Recombinant Adeno-Associated Virus-Directed Gene Therapy
James Wilson - Gladwyne PA, US Krishna Fisher - New Orleans LA, US
International Classification:
A61K031/70 A61K048/00
US Classification:
514/044000, 424/093210
Abstract:
A method of prolonging gene expression by reducing immune response to a recombinant adeno-associated virus (AAV) bearing a desired gene administered into the muscle of a mammal is described.
Method For Recombinant Adeno-Associated Virus-Directed Gene Therapy
A method of prolonging gene expression by reducing immune response to a recombinant adeno-associated virus (AAV) bearing a desired gene administered into the muscle of a mammal is described.
Recombinant Adenovirus And Adeno-Associated Virus, Cell Lines, And Methods Of Production And Use Thereof
James M. Wilson - Gladwyne PA Krishna J. Fisher - New Orleans LA Guang-Ping Gao - Havertown PA
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
A61K 4800 C12N 15861 C12N 1563 C12N 510
US Classification:
424 932
Abstract:
An adenovirus E1/E4 expressing packaging cell line is provided, which permits the generation of recombinant adenoviruses deleted in both gene regions. A method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided by infecting a target cell with a recombinant AAV comprising a selected transgene under the control of regulatory sequences. The infected cell is contacted with an agent which facilitates the conversion of single stranded recombinant virus to its double stranded form.
James M. Wilson - Gladwyne PA Krishna J. Fisher - New Orleans LA Shu-Jen Chen - Aldan PA Matthew Weitzman - La Jolla CA
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
C12Q 170 C12N 1586 C12N 1564
US Classification:
435 5
Abstract:
A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5' and 3' cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably, the helper gene is crippled by modifications to its 5' packaging sequences, which facilitates purification of the viral particle from the helper virus.
James M. Wilson - Gladwyne PA Krishna J. Fisher - New Orleans LA Shu-Jen Chen - Aldan PA Matthew Weitzman - La Jolla CA
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
C12Q 168 C12Q 170 C12N 15861 C12N 1564 C12N 510
US Classification:
435 5
Abstract:
A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5' and 3' cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably the helper gene is crippled by modifications to its 5' packaging sequences, which facilitates purification of the viral particle from the helper virus.
Hybrid Adenovirus-Aav Virus And Methods Of Use Thereof
James M. Wilson - Gladwyne PA William M. Kelley - La Honda CA Krishna J. Fisher - New Orleans LA
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
C12N 1510 C12N 701 C12N 510 C12N 1586
US Classification:
4351723
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. Also provided is a hybrid virus linked via a polycation conjugate to an AAV rep gene to form a single particle. These trans-infection particles 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 and viruses to produce large quantities of recombinant AAV.
Hybrid Adenovirus-Aav Vector And Methods Of Use Therefor
James M. Wilson - Gladwyne PA William M. Kelley - Ann Arbor MI Krishna J. Fisher - Philadelphia PA
Assignee:
The Trustees of the University of Pennsylvania - Philadelphia PA
International Classification:
C12N 1510 C12N 1564 C12N 1586
US Classification:
4351723
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.