Alisa C Dong

US Patent:

20180008725, Jan 11, 2018

Filed:

Jan 21, 2016

Appl. No.:

15/545159

Inventors:

- Ithaca NY, US
- Philadelphia PA, US
Alisa DONG - New York NY, US
Gerd BLOBEL - Bala Cynwyd PA, US
Wulan DENG - Ashburn VA, US

International Classification:

A61K 48/00
C12N 15/867

Abstract:

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 polynucleotide encoding: i) a 5′ long terminal repeat (LTR) and a self-inactivating 3′ 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.