	US 12,139,720 B2
	Recombinant lentiviral vector for stem cell- based gene therapy of sickle cell disorder
Annarita Miccio, Paris (FR); and Vasco Meneghini, Bretigny-sur-Orge (FR)
Assigned to INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM), Paris (FR); UNIVERSITE PARIS DESCARTES, Paris (FR); ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS, Paris (FR); and IMAGINE—INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES, Paris (FR)
Appl. No. 16/618,226
Filed by INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM), Paris (FR); UNIVERSITE PARIS DESCARTES, Paris (FR); ASSISTANCE PUBLIQUE—HOPITAUX DE PARIS, Paris (FR); and IMAGINE—INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES, Paris (FR)
PCT Filed Jun. 1, 2018, PCT No. PCT/EP2018/064531 § 371(c)(1), (2) Date Nov. 29, 2019, PCT Pub. No. WO2018/220210, PCT Pub. Date Dec. 6, 2018.
Claims priority of application No. 17305647 (EP), filed on Jun. 2, 2017.
Prior Publication US 2020/0190536 A1, Jun. 18, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/00 (2006.01); A61K 38/42 (2006.01); C12N 5/074 (2010.01); C12N 9/22 (2006.01); C12N 15/86 (2006.01)

CPC C12N 15/86 (2013.01) [A61K 38/42 (2013.01); C12N 5/0607 (2013.01); C12N 9/22 (2013.01); C12N 2310/20 (2017.05); C12N 2740/15043 (2013.01); C12N 2830/40 (2013.01); C12N 2830/48 (2013.01)]

22 Claims

1. A recombinant lentiviral vector comprising in its genome:

(i) a nucleotide sequence encoding a protein that has a therapeutic effect, said protein being selected from the group consisting of delta-globin and gamma globin; and

(ii) a nucleotide sequence encoding a guide RNA (gRNA) that comprises a spacer adapted to bind to a target nucleotide sequence, said target nucleotide sequence being:

a. within the coding sequence or within a transcribed non-coding sequence of a target gene, said target gene being selected from beta-globin gene and BCL11A gene, or

b. within the promoter region of a target gene, wherein said target gene is a gamma-globin gene when the nucleotide sequence (i) encoding the protein that has the therapeutic effect is delta-globin.