Chiron Corporation

Novartis Vaccines & Diagnostics, Gmbh

University of California

Cell Genesys, Inc.

Stephen F Hardy

Thomas W Dubensky, Jr

John M Polo

Silvia Perri

Lewis T Williams

Jaime A Escobedo

Jan Zur Megede

Barbara A Belli

Richard O Snyder

Pablo Dominguez Garcia

Brian Donahue

John Donnelly

Barbara Beli

Perri Silvia

A nucleic acid vector comprising: (i) a promoter; (ii) a sequence encoding a HML-2 polypeptide operably linked to said promoter; and (iii) a selectable marker. Preferred vectors comprise: (I) a eukaryotic promoter; (ii) a sequence encoding a HML-2 polypeptide downstream of and operably linked to said promoter, (iii) a prokaryotic selectable marker; (iv) a prokaryotic origin of replication; and (v) a eukaryotic transcription terminator downstream of and operably linked to said sequence encoding a HML-2 polypeptide. Vectors of the invention are particularly useful for expression of HML-2 polypeptides either in vitro (e.g. for later purification). Or in vivo (e.g. for nucleic acid immunization). They are well suited to nucleic acid immunization against prostrate tumors. A preferred HML-2 is PCAV, which is located in chromosome 22 at 20.428 megabases (22q11.2).

Nucleic acid vector comprising a promoter and a sequence encoding a polypeptide from the endogenous retrovirus PCAV

Human endogenous retroviruses of the HML-2 family show up-regulated expression in prostate tumors. This finding can be used in prostate cancer screening, diagnosis and therapy.

Endogenous retroviruses up-regulated in prostate cancer

Suppressor tRNA's are used to regulate expression of transgenes that are toxic, or the expression thereof requires a factor that is toxic, to the host cell.

Use of suppressor tRNA's to regulate cytotoxicity during the production of recombinant gene products

Methods and compositions are provided for producing recombinant AAV vector particles; comprising the general steps of (a) introducing into a host cell (i) pfloxAAV, (ii) a recombinant viral vector encoding plasmid, and (iii) a plasmid encoding herpesvirus, cytomegalovirus, or adenoviral functions, or a herpesvirus, cytomegalovirus, or, adenovirus itself, in order to produce flox AAV particles and recombinant AAV particles; and (b) introducing into a second host cell (i) the recombinant AAV particles and flox AAV particles of (a), (ii) a vector which directs the expression of Cre, and (iii) a vector which directs the expression of herpesvirus, CMV, or adenovirus helper functions, such that said recombinant AAV vector particles are produced.

Recombinant AAV packaging systems

The invention provides host cells comprising a translation operator sequence (TOP) and packaging elements. Also provided are viral vectors comprising a TOP operably linked to a transgene. Also provided are methods of using these host cells and viral vectors to produce recombinant virions.

Compositions and methods for producing recombinant virions

Nucleic acid molecule are provided comprising a nucleic acid sequence which encodes, in order, an alphavirus capsid, a signal peptide, and an alphavirus E1 or E2 glycoprotein. Also provided are vectors encoding such nucleic acid molecules, and use of such vectors or expression cassettes to generate recombinant alphavirus particles and alphavirus packaging cell lines. In addition, modified alphavirus vector constructs are provided that permit reduced transgene expression during vector packaging, as well as methods of using such vector constructs for the production of alphavirus vector particles.

Compositions and methods for packaging of alphavirus vectors

Compositions and methods for packing of alphavirus vectors

A method for producing in vivo packaged recombinant adenovirus vectors is provided. The recombinant Ad vectors do not contain any Adenovirus genes and are therefore useful for gene therapy. The recombinant Adenovirus vectors are packaged in vivo using a helper virus which is itself very inefficiently packaged, providing a recombinant viral preparation with very little or no contamination with helper virus. In particular, the method makes use of a helper virus in which the packaging site can be easily excised in vivo by recombination mediated by a recombinase. The helper virus is also useful for the in vivo construction of new recombinant adenovirus vectors containing substitutions in the E1 or other adenoviral region.

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San Francisco, CA, United States of America

Stephen F Hardy