US 12,134,767 B2
Materials and methods for treatment of hemoglobinopathies
Matthew Hebden Porteus, Stanford, CA (US)
Assigned to Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed by Vertex Pharmaceuticals Incorporated, Boston, MA (US)
Filed on Jun. 23, 2020, as Appl. No. 16/909,283.
Application 16/909,283 is a division of application No. 15/550,943, granted, now 10,738,305, previously published as PCT/IB2016/000276, filed on Feb. 23, 2016.
Claims priority of provisional application 62/119,754, filed on Feb. 23, 2015.
Prior Publication US 2021/0009998 A1, Jan. 14, 2021
Prior Publication US 2021/0317450 A9, Oct. 14, 2021
Int. Cl. C12N 15/113 (2010.01); A61K 35/28 (2015.01); A61K 35/545 (2015.01); A61K 38/42 (2006.01); A61K 48/00 (2006.01); C12N 5/074 (2010.01); C12N 5/0789 (2010.01); C12N 15/10 (2006.01); C12N 15/63 (2006.01)
CPC C12N 15/113 (2013.01) [A61K 35/28 (2013.01); A61K 35/545 (2013.01); A61K 38/42 (2013.01); A61K 48/00 (2013.01); C12N 5/0647 (2013.01); C12N 5/0696 (2013.01); C12N 15/102 (2013.01); C12N 15/63 (2013.01); C12N 2310/10 (2013.01); C12N 2310/20 (2017.05); C12N 2320/11 (2013.01); C12N 2501/73 (2013.01); C12N 2510/00 (2013.01)] 19 Claims
 
1. A method of genome editing in a cell comprising administering DNA endonuclease to the cell to effect a pair of double-strand breaks (DSBs), the first at a 5′ DSB locus and the second at a 3′ DSB locus within the δβ-globin region of human chromosome 11, causing a deletion or inversion of the chromosomal DNA between the 5′ DSB locus and the 3′ DSB locus, wherein:
(i) the 3′ boundary of the deletion is proximal to Chr11:5224779 and the 5′ boundary of the deletion is proximal to Chr11:5237723;
(ii) the 3′ boundary of the deletion is proximal to Chr11:5234665 and the 5′ boundary of the deletion is proximal to Chr11:5238138;
(iii) the 3′ boundary of the deletion is proximal to Chrll:5226631 and the 5′ boundary of the deletion is proximal to Chrll:5249422;
(iv) the 3′ boundary of the deletion is proximal to Chr11:5196709 and the 5′ boundary of the deletion is proximal to Chrll:5239223;
(v) the 3′ boundary of the deletion is proximal to Chrll:5225700 and the 5′ boundary of the deletion is proximal to Chrll:5236750;
(vi) the 3′ boundary of the deletion is proximal to Chrll:5234655 and the 5′ boundary of the deletion is proximal to Chr11:5238138; or
(vii) the 3′ boundary of the deletion is proximal to Chr11:5255885 and the 5′ boundary of the deletion is proximal to Chrll:5259368.