The Children's Hospital of Philadelphia

University of Pennsylvania

Cornell University

Cold Spring Harbor Laboratory

Gerd Blobel

Wulan Deng

Terri Helman Finkel

Stefano Rivella

Christopher Vakoc

Junwei Shi

Jiangfang Wang

Laura Breda

Alisa Dong

Jeremy Grevet

Stephan Kadauke

Provided are compositions and methods for inducing expression of human beta-globin in erythrocytes for use in prophylaxis and/or therapy of a hemoglobinopathy in an individual. The method generally entails introducing into CD34+ cells a poly-nucleotide encoding: i) a 5' long terminal repeat (LTR) and a self-inactivating 3&#x2032; LTR; ii) at least one polyadenylation signal; iii) at least one promoter; iv) a globin gene locus control region (LCR); v) an ankyrin insulator element (Ank); vi) a Woodchuck Post-Regulatory Element (WPRE) configured such that the WPRE does not integrate into a target genome; and vii) a sequence that is a reverse complement of a sequence encoding human beta-globin, and can include beta-globin that has a PT87Q mutation. Intron 2 of the beta globin gene can be a complete intron. Modified erythrocyte progenitor cells, recombinant vectors and virions comprising recombinant polynucleotides, and methods of making the vectors and virions are included.

Viral vectors for prophylaxis and therapy of hemoglobinopathies

Methods and compositions for producing fetal hemoglobin and treating a hemoglobinopathy or thalassemia are disclosed.

Compositions and methods for hemoglobin production

Methods and compositions for controlling gene expression are disclosed.

Controlled gene expression methods

Compositions and methods for the treatment of HIV are provided.

Compositions comprising a Brd4 antagonist and methods for the treatment of HIV

Growing community of inventors

Bala Cynwyd, PA, United States of America

Gerd Blobel