The Children's Hospital of Philadelphia

Spark Therapeutics, Inc.

Xavier Anguela

Katherine A High

Federico Mingozzi

Mustafa N Yazicioglu

J Fraser Wright

Sam Hsien-I Shen

The invention relates to modified Factor IX coding sequence, expression cassette, vectors such as viral (e.g., lenti- or adeno-associated viral) vectors, and gene transfer methods and uses. In particular, to target Factor IX nucleic acid to cells, tissues or organs for expression (transcription) of Factor IX.

Modified factor IX, and compositions, methods and uses for gene transfer to cells, organs, and tissues

Compositions and methods for AAV mediated gene therapy are disclosed. AAV vectors comprise protein capsid variants comprising therapeutically beneficial transgenes. AAV variants are provided which exhibit increased transduction efficiency when compared to AAV serotypes (e.g., AAV1, AAV2, AAV8, AAV-rh74), which lack the modifications disclosed herein. Such improved vectors are useful for transduction of a variety of tissues.

Composition and methods for highly efficient gene transfer using AAV capsid variants

CpG reduced nucleic acid variants encoding FVIII protein and methods of use thereof are disclosed. In particular embodiments, CpG reduced nucleic acid variants encoding FVIII are expressed more efficiently by cells, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced expression and/or activity over wild-type Factor VIII proteins or are packaged more efficiently into viral vectors.

CpG reduced factor VIII variants, compositions and methods and uses for treatment of hemostasis disorders

The invention provides viral vector formulations and methods of uses thereof for delivery of transgenes or therapeutic nucleic acids to human subjects. The formulations include a vector and suitable amounts of empty capsids, viral genome-containing capsids, or viral capsid proteins which are optionally chemically or structurally modified and which bind to neutralizing anti-AAV antibodies thereby reducing or preventing antibody-mediated clearance of the vector, but still allowing the genome-containing (therapeutic) vector to transduce target cells and achieve therapeutic gene transfer.

Virus vectors for highly efficient transgene delivery

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 and related AAV vectors target 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.

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Philadelphia, PA, United States of America

Xavier Anguela