University of Florida Research Foundation, Incorporated

The University of North Carolina at Chapel Hill

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Intima Bioscience, Inc.

Mavis Agbandje-McKenna

Arun Srivastava

Sergei Zolotukhin

George Vladimirovich Aslanidi

Kim M Van Vliet

Li Zhong

Lakshmanan Govindasamy

Mario Mietzsch

Aravind Asokan

Brittney Gurda

Long Ping Victor Tse

Richard Jude Samulski

Chengwen Li

Joseph E Rabinowitz

Robert McKenna

Dawn E Bowles

Josh Grieger

John A Chiorini

William W Hauswirth

Modassir Choudhry

Sanford Leon Boye

Shannon Elizabeth Boye

Damien Marsic

Chen Ling

Thomas Henley

Tilmann Buerckstuemmer

Sanford L Boye

Shannon E Boye

Sandra Wainer

Sujata Halder

Kirsten Ariane Kelley Weigel-Van Aken

Lydia Viney

James K Smith

Patrick Havlik

Disclosed are capsid-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations containing them. Also provided are methods of preparing and using the disclosed capsid-protein-mutated rAAV constructs in a variety of diagnostic and therapeutic modalities, including, inter alia, as mammalian cell-targeting delivery agents, and as human gene therapy vectors. Also disclosed are large-scale production methods for capsid-modified rAAV expression vectors, viral particles, and infectious virions having improved transduction efficiencies over those of the corresponding, un-modified, rAAV vectors, as well as use of the disclosed compositions in the manufacture of medicaments for a variety of in vitro and/or in vivo applications.

Capsid-modified rAAV vector compositions and methods therefor

The present disclosure provides AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the modified AAV capsid protein. The disclosure also provides methods of administering the virus vectors and virus capsids of the disclosure to a cell or to a subject in vivo. This disclosure also relates to recombinant adeno associated virus (rAAV) capsid proteins comprising one or more amino acid substitutions in the 5-fold region of the rAAV capsid that result in decreased reactivity to neutralizing antibodies, and their use as gene delivery vehicles.

Methods and compositions for antibody-evading virus vectors

Provided herein are compositions and methods for packaging a recombinant adeno-associated virus (rAAV) particle comprising using inverted terminal repeats (ITRs) and rep genes of different serotypes and/or using chimeric rep genes.

AAV chimeras

The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.

High-transduction-efficiency rAAV vectors, compositions, and methods of use

This disclosure relates to variant AAVrh 10 particles engineered to escape host neutralizing antibodies but retain or improve transduction efficiency, and their use as gene delivery vehicles.

AAVrh.10 variants with host antibody escape capabilities and altered tissue targeting properties

Provided herein are compositions and methods for packaging a recombinant adeno-associated vims (rAAV) particle comprising using inverted terminal repeats (ITRs) and rep genes of different serotypes and/or using chimeric rep genes.

The present invention provides AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the modified AAV capsid protein. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject in vivo.

AAV vectors with high transduction efficiency and uses thereof for gene therapy

Genetically modified compositions, such as adeno-associated viral vectors and primary cells, for treating various conditions and diseases. Disclosed are also modified adeno-associated viruses for the treatment of cancer. Also disclosed are the methods of making and using the genetically modified compositions in treating various diseases, conditions, and cancer.

Adeno-associated viral vectors for gene therapy

Disclosed are compositions and methods for producing modified adeno-associated virus (AAV) cap genes and combinatorial libraries of chimeric AAV vectors and virions; selecting for virions displaying cell-specific tropisms; and, in certain embodiments, producing helper vectors containing one or more modified AAV cap genes. The synthetic combinatorial AAV capsid libraries of the invention are useful in introducing into selected target host cells one or more nucleic acid molecules. The viral vectors and genetic constructs disclosed herein are also useful in a variety of diagnostic and/or therapeutic gene-therapy regimens.

Synthetic combinatorial AAV capsid library for targeted gene therapy

This disclosure relates to variant AAVrh.10 particles engineered to escape host neutralizing antibodies but retain or improve transduction efficiency, and their use as gene delivery vehicles.

Disclosed are next-generation multi-mutated capsid protein-modified rAAV expression vectors, as well as infectious virions, compositions, and pharmaceutical formulations that include them. Also disclosed are methods of preparing and using these high transduction efficiency vector constructs in a variety of therapeutic applications including, inter alia, as delivery agents for the treatment or amelioration of one or more diseases or abnormal conditions in an affected mammal using in vivo and/or ex situ viral vector-based gene therapy protocols. Also disclosed are large-scale production methods for the multi-mutated, capsid-modified rAAV expression vectors, viral particles, and infectious virions, as well as use of the disclosed compositions in the manufacture of medicaments for use in a variety of in vitro and/or in vivo therapeutic methodologies.

Capsid-modified, RAAV3 vector compositions and uses in gene therapy of human liver cancer

Provided herein are modified recombinant adeno-associated virus (rAAV) capsid proteins, such as modified rAAV1, rAAV5, and rAAV6 capsid proteins, rAAV particles comprising such capsid proteins, nucleic acid molecules encoding such capsid proteins, as well as compositions, kits and methods of use thereof.

Recombinant AAV1, AAV5, and AAV6 capsid mutants and uses thereof

Growing community of inventors

Gainesville, FL, United States of America

Mavis Agbandje-McKenna