University of Pennsylvania

Ascidian Therapeutics, Inc.

Krishna J Fisher

James M Wilson

William M Kelley

Guang-Ping Gao

Jean Bennett

Junwei Sun

Philip R Johnson

Bruce C Schnepp

Scott J Dooley

Matthew Weitzman

Shu-Jen Chen

Steven F Farina

The present invention features nucleic acid trans-splicing molecules (e.g., pre-mRNA trans-splicing molecules (RTMs)) capable of correcting one or more mutations in the ABCA4 gene or the CEP290 gene. Such molecules are useful in the treatment of disorders associated with mutations in ABCA4, such as Stargardt Disease (e.g., Stargardt Disease 1) and disorders associated with a mutation in CEP290, such as Leber congenital amourosis 10 (LCA 10). Also provided by the invention described herein are methods of using the nucleic acid trans-splicing molecules for correcting mutations in ABCA4 and CEP290 and for treating disorders associated with mutations in ABCA4 and CEP290, such as Stargardt Disease and LCA 10.

Trans-splicing molecules

The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5&prime; and 3&prime; ITR sequences from an AAV, and a selected transgene. Other hybrid vectors form a polycation conjugate and incorporate an AAV rep gene in a single particle. These hybrid virus vectors are characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. Also disclosed is the use of the hybrid vectors to produce large quantities of recombinant AAV.

Hybrid adenovirus-AAV virus and methods of use thereof

An adenovirus E1/E4 expressing packaging cell line is provided, which permits the generation of recombinant adenoviruses deleted in both gene regions. A method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided by infecting a target cell with a recombinant AAV comprising a selected transgene under the control of regulatory sequences. The infected cell is contacted with an agent which facilitates the conversion of single stranded recombinant virus to its double stranded form.

Recombinant adenovirus and adeno-associated virus, cell lines and methods of production and use thereof

Recombinant adenovirus and adeno-associated virus, cell lines, and methods of production and use thereof

The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5&prime; and 3&prime; ITR sequences from an AAV, and a selected transgene. Also provided is a hybrid virus linked via a polycation conjugate to an AAV rep gene to form a single particle. These trans-infection particles are characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. Also disclosed is the use of the hybrid vectors and viruses to produce large quantities of recombinant AAV.

A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5&prime; and 3&prime; cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably the helper gene is crippled by modifications to its 5&prime; packaging sequences, which facilitates purification of the viral particle from the helper virus.

Adenovirus and method of use thereof

A recombinant vector comprises chimpanzee adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses chimpanzee adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Chimpanzee adenovirus vectors

Adenovirus and methods of use thereof

A method of gene transfer involving administering a recombinant adeno-associated virus (AAV) bearing the desired gene into the muscle of the animal is described.

Method for expressing a gene in the absence of an immune response

The present invention provides a hybrid vector construct which comprises a portion of an adenovirus, 5' and 3' ITR sequences from an AAV, and a selected transgene. Other hybrid vectors form a polycation conjugate and incorporate an AAV rep gene in a single particle. These hybrid virus vectors are characterized by high titer transgene delivery to a host cell and the ability to stably integrate the transgene into the host cell chromosome. Also disclosed is the use of the hybrid vectors to produce large quantities of recombinant AAV.

Hybrid adenovirus-AAV vector and methods of use therefor

A method for enhancing the efficiency of transduction of a recombinant AAV into a target cell is provided. The target cell is infected with a recombinant adeno-associated virus comprising a selected transgene under the control of regulatory sequences. The infected cell is contacted with an agent which facilitates the conversion of single stranded recombinant virus to its double stranded form. When this conversion occurs in the target cell, enhanced transduction of the recombinant virus into said target cell results. The agent can be a helper virus providing a gene which facilitates the conversion, or an agent to which the infected cell is exposed, which facilitates the conversion. In a similar manner, a novel recombinant AAV is provided which contains the facilitating gene and the transgene. The methods may be performed ex vivo or in vivo.

Growing community of inventors

New Orleans, LA, United States of America

Krishna J Fisher