Leland Stanford Junior University

University of Washington

Other

Bristol-Myers Squibb Compnay

Oregon Health & Science University

Cell Genesys, Inc.

Benitec Biopharma Limited

Benitec, Inc.

The University of Texas System

Mark A Kay

Zhi-Ying Chen

Dirk Grimm

Andre Lieber

Jiamiao Lu

Leszek Lisowski

Anton McCaffrey

Shengchun Wang

Nicole K Paulk

Hak Kyun Kim

David A Suhy

Joseph C Wu

Hiroyuki Mizuguchi

Dirk Haussecker

Dan Cao

Adi Barzel

Katja Pekrun

Jeffrey A Ledbetter

Peter S Linsley

Alejandro A Aruffo

Michael T Longaker

Andrew Fire

Matthew Hebden Porteus

Petrus W Roelvink

Markus Grompe

Richard O Snyder

Lawrence K Cohen

Alexander A Kolykhalov

Diane L Hollenbaugh

Olivier Danos

Mei Huang

Muhsen Al-Dhalimy

Micheal Hebert

Jeffery C Giering

Lia E Gracey Maniar

Stephen Yant

Carol H Miao

Hiroyuki Nakai

Anja Ehrhardt

Arthur R Thompson

Kazuo Ohashi

Steve Yant

Matt Tiffany

Christopher B Wilson

Ning Sung

FangJun Jia

Nicholas Panetta

Deepak Gupta

Hisaya Azuma

Josh Checketts

Richard Voit

Jenny Barker

Anton Mccaffrey

NOVEL RECOMBINANT ADENO-ASSOCIATED VIRUS CAPSIDS WITH ENHANCED HUMAN PANCREATIC TROPISM

Methods and compositions are provided for editing the genome of a cell without the use of an exogenously supplied nuclease. Aspects of the methods include contacting a cell with a targeting vector comprising nucleic acid sequence to be integrated into the target locus, where the cell is not also contacted with a nuclease. In addition, reagents, devices and kits thereof that find use in practicing the subject methods are provided.

Genome editing without nucleases

The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human pancreatic tissue or human islets as compared non-variant parent capsid polypeptides.

Recombinant adeno-associated virus capsids with enhanced human pancreatic tropism

Provided are nucleic acids and expression vectors having a non-silencing selectable marker gene, and methods of using the same. A subject expression vector includes an expression cassette and a non-silencing selectable marker gene. In some cases, the non-silencing selectable marker gene provides for drug resistance for prokaryotic cells, and includes a nucleotide sequence that (i) encodes a drug selectable marker protein; (ii) is operably linked to a promoter functional in prokaryotic cells, and (iii) includes an increased A/T content relative to a corresponding wild type nucleotide sequence. In some cases, the non-silencing selectable marker gene provides for drug resistance for prokaryotic cells, and includes a nucleotide sequence that (i) encodes a drug selectable marker protein; (ii) is operably linked to a promoter functional in prokaryotic cells, and (iii) has an A/T content in a range of from 52% to 70%.

Non-silencing selectable marker genes and methods of use

Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

AAV capsid proteins for nucleic acid transfer

The present invention features compositions and methods relating to tRNA-derived small RNAs (tsRNAs). Provided herein are oligonucleotide compositions that are complementary to tsRNAs, in particular leuCAGtsRNA, and methods of using the oligonucleotides for the regulation of respective tsRNA. Further provided are methods of inducing apoptosis through the inhibition of leuCAGtsRNA.

tRNA derived small RNAs (tsRNAs) involved in cell viability

Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

Circular nucleic acid vectors, and methods for making and using the same

Methods and compositions are provided for modulating, e.g., reducing, viral coding sequence expression in mammals and mammalian cells. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is introduced into a target cell, e.g., by being administered to a mammal that includes the target cell, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

Methods and compositions for RNAi mediated inhibition of gene expression in mammals

The present invention relates to variant AAV capsid polypeptides, wherein the variant capsid polypeptides exhibit an enhanced neutralization profile, increased transduction and/or tropism in human liver tissue or hepatocyte cells (i.e., human hepatocyte cells), or both, as compared non-variant parent capsid polypeptides.

Recombinant adeno-associated virus capsids resistant to pre-existing human neutralizing antibodies

Methods and compositions are provided for modulating, e.g., reducing, coding sequence expression in mammals. In the subject methods, an effective amount of an RNAi agent, e.g., an interfering ribonucleic acid (such as an siRNA or shRNA) or a transcription template thereof, e.g., a DNA encoding an shRNA, is administered to a non-embryonic mammal, e.g., via a hydrodynamic administration protocol. Also provided are RNAi agent pharmaceutical preparations for use in the subject methods. The subject methods and compositions find use in a variety of different applications, including academic and therapeutic applications.

The present invention relates to AAV vectors encoding variant capsid polypeptides that are more cationic as compared to a non-variant parent capsid polypeptide and/or another variant capsid polypeptide, and wherein the vector comprising the variant capsid polypeptide is capable of comprising a longer nucleic acid insert as compared to a vector encoding a non-variant parent capsid polypeptide and/or another variant capsid polypeptide.

AAV vectors with expanded packaging capacity

The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human muscle tissue or cells as compared non-variant parent capsid polypeptides.

Recombinant adeno-associated virus capsids with enhanced human skeletal muscle tropism

Growing community of inventors

Los Altos, CA, United States of America

Mark A Kay