University of Pennsylvania

Ascidian Therapeutics, Inc.

University of California

Centre National De La Recherche Scientifique

Institut National De La Sante Et De La Recherche Medicale

University of Southern California

The Children's Hospital of Philadelphia

Mcgill University

Université Pierre Et Marie Curie (paris 6)

Inserm

Junwei Sun

Jean Bennett

Jeannette Bennicelli

Krishna J Fisher

Philip R Johnson

Bruce C Schnepp

Scott J Dooley

Vidyullatha Vasireddy

Ji Yun Song

Jose-Alain Sahel

Katherine A High

John G Flannery

Federico Mingozzi

Devin McDougald

Thierry Leveillard

Leah Caroline Thomas Byrne

Leah C Byrne

Catherine Argyriou

Nancy Braverman

Joseph Hacia

Kenneth Shindler

Ahmara Gibbons Ross

Xin Mei

Emmanuelle Clerin-Lachapelle

Philip Johnson

José-Alain Sahel

Sergei Nikonov

Jeanette Bennicelli

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

Codon optimized nucleic acid sequences for RDH12 are provided, as well as recombinant viral vectors, such as AAV, expression cassettes, proviral plasmids or other plasmids containing the codon optimized sequence for functional RDH12. Recombinant vectors are provided that express the codon optimized, functional RDH12. Compositions containing these codon optimized sequences are useful in methods for treating, retarding or halting certain blinding diseases resulting from the absence, deficiency or inappropriate expression of RDH12. Other compositions and methods are providing for correcting a non-functional, defective or inadequately expressed native RDH12.

Methods and compositions for treatment of disorders and diseases involving RDH12

Compositions and methods are provided for treating ocular disorders in a subject are provided. In one aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGA3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding CNGB3. In another aspect, an adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding REP-1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Gene therapy for ocular disorders

Codon optimized nucleic acid sequences for the long form and short form of RdCVF are provided, as well as recombinant viral vectors, such as AAV, expression cassettes, proviral plasmids or other plasmids containing the codon optimized sequences. Recombinant vectors are provided that express the codon optimized RdCVFL and RdCVF individually, or express two copies of a codon optimized RdCVF or RdCVFL nucleic acid sequence, or both RdCVFL and RdCVF in a single vector or virus. Compositions containing these codon optimized sequences are useful in methods for treating, retarding or halting certain blinding diseases resulting from the absence or inappropriate expression of RdCVF and RdCVFL.

Methods and compositions for treatment of ocular disorders and blinding diseases

The invention relates to adeno-associated virus (AAV) serotype AAV-Rh74 and related AAV vectors, and AAV-Rh74 and related AAV vector mediated gene transfer methods and uses. In particular, AAV-Rh74 targets polynucleotides to cells, tissues or organs for expression (transcription) of genes encoding therapeutic proteins and peptides, and polynucleotides that function as or are transcribed into inhibitory nucleic acid sequences.

AAV vector compositions and methods for gene transfer to cells, organs and tissues

Compositions and methods are provided for treating ocular neuropathy in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding NRF2. In another aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding SIRT1. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Methods and compositions are provided for treatment of peroxisomal biogenesis disorders (PBDs). More particularly, recombinant adeno-associated viruses (rAAV) provided in the form of compositions are used to deliver a nucleic acid encoding human PEX1 to host cells. The rAAVs comprise a AAV capsid, and packaged therein a vector genome comprising an AAV 5' inverted terminal repeat (ITR) sequence; a promoter; a coding sequence encoding a human PEX1; and an AAV 3&#x2032; ITR.

Gene therapy for treating peroxisomal disorders

Compositions and methods are provided for treating Leber congenital amaurosis (LCA) in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding Lebercilin. In another aspect, Lebercilin has an amino acid sequence of SEQ ID NO: 1. In yet another aspect, the nucleic acid molecule has a sequence of SEQ ID NO: 3 or a variant thereof. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

The present invention relates to the synergistic combination of the short and long Rod-Derived Cone Viability Factors and to methods for treating retinal degenerative diseases.

Synergistic combination of neuronal viability factors and uses thereof

Growing community of inventors

Philadelphia, PA, United States of America

Junwei Sun