Other

University of California

Biogen, Incorporated

Advanced Genetic Systems, Inc.

Alan Frankel

R Blake Pepinsky

James G Barsoum

Carl Pabo

Stephen E Fawell

Robert Nakamura

Adam Renslo

Derek Hudson

Mark A Burlingame

Ruoying Tan

Chandreyee Das

Ivan D'Orso

Jocelyn Grunwell

Shelley S Martin

Kazuo Harada

Provided herein, inter alia, are methods and compounds for treating an HIV infection.

Compounds and methods for treating HIV infection

The present invention provides methods and compositions for regulating gene expression using transcription factors linked to proteins that localize to the transcriptional machinery.

Generation of potent dominant negative transcriptional inhibitors

This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which include HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation. The reduced size of the preferred transport polypeptides of this invention also minimizes interference with the biological activity of the cargo molecule.

Tat-derived transport polypeptides

The invention provides methods and kits suitable for large-scale in vivo screening of polypeptides for specific binding affinity to a selected RNA recognition sequence. Polypeptide(s) are screened as fusion proteins with a polypeptide having antitermination activity. Polypeptides having binding activity are identified by their capacity to activate transcription of a reporter gene via binding of the polypeptide being screened to the selected RNA recognition sequence. The invention also provides methods of screening RNA molecules for binding to a selected polypeptide.

In vivo selection of RNA-binding peptides

This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which comprise HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation. The reduced size of the preferred transport polypeptides of this invention also minimizes interference with the biological activity of the cargo molecule.

Tat-derived transport polypeptides and fusion proteins

Tat-derived transport polypeptide conjugates

Fusion protein comprising tat-derived transport moiety

Nucleic acid conjugates of tat-derived transport polypeptides

Compositions and methods for identifying compositions which inhibit binding of the Rev protein to the Rev-responsive element in cells infected by HIV-1 are provided. The compositions display or mimic the electronic configuration of a binding domain within the native Rev protein, but are free from those portions responsible for REV activity and are preferably modified to display enhanced binding affinity to the RRE. Screening methods for identifying polypeptides and other compositions having such enhanced binding affinity are also described.

Compositions and methods for inhibiting replication of human

Nucleic acids encoding and methods of making tat-derived transport

Growing community of inventors

Tiburon, CA, United States of America

Alan Frankel