University of California

Gunter Kraus

Flossie Wong-Staal

Eric M Poeschla

Pierre Corbeau

Randy L Talbott

Mang Yu

Osamu Yamada

Mark Leavitt

Michael Mamounas

By transducing cells with an HIV-1-MN molecular clone deleted in the major packaging sequence, a stable HIV-1 packaging cell line, &psgr;422 was produced. &psgr;422 cells form syncytia with CD4 positive cells, correctly express HIV-1 structural proteins, and produce large amount of mature particles with normal RT activity. These particles are not infectious. When stably transfected with an HIV-based retroviral vector, the &psgr;422 cell line produces hybrid virions capable of transducing CD4 positive cells with high efficiency (e.g., 10,cells/ml). The availability of this stable, noninfectious HIV-1 packaging cell line capable of generating high titer HIV vectors enables the use of HIV-1 based nucleic acids delivery systems, for example, in gene therapy. An HIV-2 based vector is packaged by the packaging cell lines, demonstrating that HIV-2 cell transformation vectors are packaged by the packaging cell line. HIV based vectors packaged by the high efficiency cell lines are shown to have anti-HIV activity per se.

Design of novel highly efficient HIV based packaging systems for gene therapy

Novel HIV-2 proviruses, molecular clones, nucleic acids, polypeptides, viruses and viral components are described. The use of these compositions as components of diagnostic assays, as immunological reagents, as vaccines, as components of packaging cells, cell transduction vectors, and as gene therapy vectors is also described.

Polypeptides encoded by novel HIV-2 proviruses

Cell transformation vector comprising an HIV-2 packaging site nucleic acid and an HIV-1 GAG protein

Methods and compositions for the treatment and diagnosis of infections of Rev-binding primate lentiviruses are provided. These methods and compositions utilize the ability of Rev binding nucleic acids such as the SLII sequence from the HIV-1 Rev response element (RRE) to target therapeutic agents to the same sub-cellular location as primate lentiviruses which contain RRE sequences. In particular, the invention provides trans-acting ribozymes comprising Rev-binding nucleic acids less toxic than a full-length RRE, and molecules encoding them. The use of the compositions of the invention as components of diagnostic assays, as prophylactic reagents, and in vectors is also described.

Chimeric antiviral agents comprising Rev binding nucleic acids and

Isolation of novel HIV-2 proviruses

Vectors are provided which stably transduce cells, rendering the cells resistant to a target virus. The vectors are amplified upon infection of the cell by a target virus, and spread throughout an infected host in response to infection by the target virus.

Viral vectors

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Miami, FL, United States of America

Gunter Kraus