Massachusetts Eye and Ear Infirmary

The Schepens Eye Research Institute, Inc.

Bluebird Bio, Inc.

Ultragenyx Pharmaceutical Inc.

Christopher Tipper

Luk H Vandenberghe

Eric Zinn

Olivier Negre

Melissa Bonner

Aubrey R Tiernan

Pauline Schmit

Carmen Unzu

Kelly Reed Clark

This disclosure provides compositions and methods for altering or changing the tissue tropism, e.g., liver tropism, of adeno-associated viruses (AAV).

Altering tissue tropism of adeno-associated viruses

The invention relates to methods of culturing cells, generating cell lines, and delivering polynucleotides to cells involving the use of HDAC inhibitors and/or adeno-associated virus (AAV) rep proteins.

Cell culture methods involving HDAC inhibitors or rep proteins

The invention provides improved gene therapy methods and compositions. In particular embodiments, gene therapies comprise hematopoietic stem and progenitor cell compositions with increased therapeutic efficacy and methods of making and using the same. In other particular embodiments, the present invention contemplates compositions and methods for increasing transduction efficiency and vector copy number (VCN) of human hematopoietic stem and progenitor cells (HSPCs) to yield improved gene therapy compositions. In various embodiments, the present invention contemplates, in part, a population of HSPCs transduced with a lentiviral vector. In various embodiments, the present invention contemplates a method of treating sickle cell disease in a subject comprising administering the subject an effective amount of the population of hematopoietic cells contemplated herein. In various embodiments, the present invention contemplates a kit comprising an agent that increases prostaglandin EP receptor signaling and staurosporine.

VCN enhancer compositions and methods of using the same

Growing community of inventors

Cambridge, MA, United States of America

Christopher Tipper